SNPMiner Trials by Shray Alag

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SNPMiner SNPMiner Trials (Home Page)


Report for Mutation R132H

Developed by Shray Alag, 2020-2021.
SNP Clinical Trial Gene

There are 12 clinical trials

Clinical Trials


1 Oral ONC201 in Recurrent Glioblastoma, H3 K27M-mutant Glioma, and Diffuse Midline Glioma

ONC201 is a new drug candidate that kills cancer cells but not normal cells in laboratory studies and has been previously evaluated in a phase I clinical trial in advanced cancer patients. This clinical trial will enroll patients with recurrent glioblastoma or recurrent WHO Grade IV gliomas with the H3 K27M mutation.

NCT02525692
Conditions
  1. Glioblastoma
  2. Diffuse Midline Glioma
  3. H3 K27M Glioma
  4. Thalamic Glioma
  5. Infratentorial Glioma
  6. Basal Ganglia Glioma
Interventions
  1. Drug: ONC201
MeSH:Glioblastoma Glioma
HPO:Glioblastoma multiforme Glioma

Tumors with isocitrate dehydrogenase 1 (IDH1) or IDH2 mutations as determined by immunohistochemistry for the IDH1 R132H variant or by direct sequencing. --- R132H ---

Primary Outcomes

Measure: Progression-free survival

Time: 6 months

2 Phase 1 / 2 Trial of Blood-brain Barrier Opening With an Implantable Ultrasound Device SonoCloud-9 and Treatment With Albumin-bound Paclitaxel in Patients With Recurrent Glioblastoma

Paclitaxel is among the most active agents against glioblastoma in preclinical models. However, its clinical use has been hampered by the blood-brain barrier (BBB). In this trial we will implant a novel device with 9 ultrasound emitters allowing to temporarily and reversibly open the BBB immediately prior to chemotherapy infusion with albumin-bound paclitaxel. In this phase 1 trial increasing doses of chemotherapy will be delivered as long deemed safe and prior patient had not experienced severe toxicity. Once the the recommended dosing has been established, additional patients will be treated in order to better evaluate the antitumor efficacy of this novel treatment. The device will be implanted at the time of surgical resection of the recurrent tumor. During that procedure a first test dose of the chemotherapy will be administered in the operating room after sonication (procedure of activating ultrasound and opening the BBB) and tissue concentrations in different parts of the resected tumor will be measured. In select patients, the sonication procedure will occur immediately after the test dose of chemotherapy is administered. The objectives of this trial are to establish a safe and effective dose of ABX, to demonstrate that the opening of the BBB increases chemotherapy concentration in the tumor, and to estimate how effective this treatment is in reducing the tumor burden and prolonging life.

NCT04528680
Conditions
  1. Glioblastoma
  2. Gliosarcoma
  3. GBM
  4. Glioblastoma Multiforme
  5. Glioblastoma, IDH-wildtype
  6. Recurrent Glioblastoma
Interventions
  1. Device: Sonication for opening of blood-brain barrier
  2. Drug: Chemotherapy, albumin-bound paclitaxel
MeSH:Glioblastoma Gliosarcoma
HPO:Glioblastoma multiforme

IDH R132H neg) 2. Ability to undergo contrast-enhanced MRI 3. Radiographic evidence of tumor recurrence/progression after failure of 1 - 2 lines of prior therapy 4. Measurable or evaluable disease 1. Measurable: contrast-enhancement (bidirectional diameters ≥ 1cm) on MRI 2. Non-measurable/evaluable: contrast-enhancement diameters < 1 cm 5. Maximal tumor diameter pre-surgery ≤ 70 mm on T1wMRI 6. Candidate for at least partial surgical resection 7. Greater 12 weeks from completion of radiation therapy 8. Age ≥ 18 years 9. Stable or decreasing dose of corticosteroids equivalent to ≤ 6 mg dexamethasone, for ≥ 7 days prior to registration 10. --- R132H ---

Primary Outcomes

Description: Occurrence of ≥ grade 3 treatment related toxicity

Measure: Dose limiting toxicity

Time: 1st treatment cycle = 3 weeks

Description: Survival time from date of tumor resection and device implantation

Measure: 1-year survival rate

Time: 12-months

Secondary Outcomes

Description: Safety and tolerance

Measure: Incidence of side effects/toxicity associated with Sonication/ABX treatment

Time: 12 months

Other Outcomes

Description: increase in Gd contrast enhancement post sonication

Measure: Extent of tumor and peritumoral tissue covered by BBB opening

Time: 1st cycle (cycle = 3 weeks)

Description: measurement of tumor shrinkage (if there is residual disease)

Measure: Objective response rate (RANO)

Time: 6 months

Description: compare before and after sonication

Measure: Measurement of circulating tumor DNA, methods and units for this measure are to be determined and still under evaluation.

Time: 1st cycle, cycles 2 - 6 as applicable (cycle = 3 weeks)

3 A Phase 1, Multicenter, Randomized, Controlled, Open-Label, Perioperative Study of AG-120 and AG-881 in Subjects With Recurrent, Non-Enhancing, IDH1 Mutant, Low Grade Glioma

Study to evaluate the suppression of 2-HG (2-hydroxyglutarate) in IDH-1 mutant gliomas in resected tumor tissue following pre-surgical treatment with AG-120 or AG-881.

NCT03343197
Conditions
  1. Glioma
Interventions
  1. Drug: AG-120
  2. Drug: AG881
MeSH:Glioma
HPO:Glioma

3. Have documented IDH1 R132H gene mutation by local testing and known 1p19q or ATRX mutation status by local testing. --- R132H ---

Glioma Glioma A phase-1, multi-center study in recurrent non-enhancing gliomas with IDH1 R132H mutation for patients who require surgery. --- R132H ---

The safety, tolerability, PK/PD, and anti tumor activity data from the study in subjects with recurrent non-enhancing Grade 2/3 LGG with an IDH1 R132H mutation for whom surgical resection is indicated will identify the recommended dose of AG-120 and AG-881 for future studies in glioma. --- R132H ---

Primary Outcomes

Measure: 2-HG concentration in surgically resected tumors

Time: Up to 4 weeks, on average

Secondary Outcomes

Measure: Safety and tolerability: incidence of adverse events and serious adverse events

Time: Up to 48 weeks, on average

Measure: Pharmacodynamics of AG-120 or AG-881 measured by 2-HG concentration in plasma.

Time: Up to 4 weeks, on average

Measure: Peak Plasma Concentration (Cmax) of AG-120 or AG-881

Time: Up to 4 weeks, on average

Measure: Time to maximum concentration (Tmax) of AG-120 or AG-881

Time: Up to 4 weeks, on average

Measure: Area Under the Curve (AUC) of AG-120 or AG-881

Time: Up to 4 weeks, on average

Measure: Elimination half-life of AG-120 or AG-881

Time: Up to 4 weeks, on average

Measure: Clinical activity associated with AG-120 or AG-881 according to modified RANO_LGG criteria.

Time: Up to 48 weeks, on average

4 INdividualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT)

This research study is studying several investigational drugs as a possible treatment for Glioblastoma (GBM). The drugs involved in this study are : - Abemaciclib - Temozolomide (temodar) - Neratinib - CC115

NCT02977780
Conditions
  1. Glioblastoma
Interventions
  1. Drug: Temozolomide
  2. Drug: Neratinib
  3. Drug: CC-115
  4. Drug: Abemaciclib
MeSH:Glioblastoma
HPO:Glioblastoma multiforme

- Immunohistochemically negative for IDH1 R132H mutation. --- R132H ---

Primary Outcomes

Measure: Overall Survival in Experimental Arms Compared with Standard Therapy

Time: 2 years

Secondary Outcomes

Description: Safety will be assessed by quantifying the toxicities and grades experienced by subjects, including serious adverse events (SAEs). The following will also be measured as part of safety: laboratory safety assessments, KPS status, vital signs and physical examinations.

Measure: Incidence of Treatment-Emergent Adverse Events

Time: 2 years

Measure: Progression Free Survival Among Experimental Arms And Biomarker Groups

Time: 2 years

Measure: Overall Survival Among Experimental Arms And Biomarker Groups

Time: 2 years

Measure: Association Between Progression Free Survival and Overall Survival Effects Of Experimental Agents

Time: 2 years

5 A Phase 2 Study of the PARP Inhibitor Olaparib (AZD2281) in IDH1 and IDH2 Mutant Advanced Solid Tumors

This phase II trial studies how well olaparib works in treating patients with glioma, cholangiocarcinoma, or solid tumors with IDH1 or IDH2 mutations that have spread to other places in the body (metastatic) and usually cannot be cured or controlled with treatment (refractory). Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

NCT03212274
Conditions
  1. Advanced Malignant Solid Neoplasm
  2. Glioblastoma
  3. Recurrent Cholangiocarcinoma
  4. Recurrent Glioma
  5. Recurrent Malignant Solid Neoplasm
  6. WHO Grade II Glioma
  7. WHO Grade III Glioma
Interventions
  1. Drug: Olaparib
MeSH:Neoplasms Glioblastoma Glioma Cholangiocarcinoma
HPO:Cholangiocarcinoma Glioblastoma multiforme Glioma Neoplasm

Summary statistics will be reported (with 95% confidence intervals) to demonstrate mean differences in fold-change (or log fold-change) between responders and non-responders.. Inclusion Criteria: - Subjects must be able to understand the nature of this trial and provide written informed consent, prior to any study specific procedures; patients with Impaired Decision Making Capacity (IDMC) who have a close caregiver or legally authorized representative (LAR) may be considered eligible for this study at the treating physician's discretion, provided that the physician is reasonably sure that the possible risks and benefits of the study are clear and that the patient will take the drug as prescribed - Subjects must be diagnosed with a glioma, cholangiocarcinoma or other solid malignant tumor that has progressed despite standard therapy, or for which no effective standard therapy exists, with biopsy-confirmed evidence of an IDH1 or IDH2 mutation associated with neomorphic activity of the encoded proteins; patients must have IDH1 or IDH2 mutation which must be detected in a clinical accredited laboratory using a Food and Drug Administration (FDA)-approved molecular test or a validated deoxyribonucleic acid (DNA)-based assay conducted in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory; only specific mutations that lead to a neomorphic phenotype will be eligible for enrollment, and include IDH1: R132V, R132G, R132S, R132L, R132C and R132H; IDH2: R140W, R140L, R140Q, R172W, R172G, R172S, R172M, R172K - Patients must have tumors determined to be easily accessible for biopsy and must be willing to have serial biopsies (with a third biopsy upon evidence of disease progression); in case of multiple lesions, tumor biopsies will be performed on the most accessible site of disease; all possible precautions to avoid complications will be taken, including discussions in multidisciplinary meetings, if needed; patients affected by glioma will not be considered for study biopsies - Patients must be willing to undergo extra blood sampling for correlative studies - Subjects with extracranial disease must have evaluable disease by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1); subjects affected by glioma must have evaluable disease by Response Assessment in Neuro-Oncology Criteria (RANO) criteria - For subjects with glioma, specific inclusion criteria are as follows: - The disease should be recurrent or transformed glioma; subjects must not have had prior surgery (biopsy allowed) or radiation therapy within 3 weeks of enrollment - There must be an enhancing component of disease, as evaluated on pre-treatment magnetic resonance imaging (MRI) - For patients with World Health Organization (WHO) grade III or IV glioma and progressive disease < 12 weeks after completion of chemoradiotherapy, progression can be defined by the following set of criteria: - New enhancement outside of the radiation field (beyond the high-dose region or 80% isodose line) - If there is unequivocal evidence of viable tumor on histopathologic sampling (e.g., solid tumor areas. --- R132V --- --- R132G --- --- R132S --- --- R132L --- --- R132C --- --- R132H ---

bosentan, efavirenz, modafinil); the required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents; because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated drug information reference; medical reference texts such as the Physicians' Desk Reference may also provide this information; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product - Persistent toxicities caused by previous cancer therapy; toxicities should have recovered to =< grade 1, excluding alopecia and stable chronic grade 2 toxicity that is not overlapping with presumed toxicities of olaparib - Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML - Patients with symptomatic uncontrolled brain metastases; a scan to confirm the absence of brain metastases is not required; the patient can receive a stable dose of corticosteroids before and during the study if these were started at least 4 weeks prior to treatment; patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days; patients with known uncontrolled brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events - Major surgery within 2 weeks of starting study treatment; effects from surgeries should have recovered to =< grade 1, with the exception of stable chronic grade 2 that is not overlapping with presumed toxicities of olaparib - Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection; examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent and would limit compliance with study requirements - Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication - Women who are actively breast feeding - Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV); HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Olaparib; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated - Patients with a known hypersensitivity to olaparib or any of the excipients of the product; history of allergic reactions attributed to compounds of similar chemica Inclusion Criteria: - Subjects must be able to understand the nature of this trial and provide written informed consent, prior to any study specific procedures; patients with Impaired Decision Making Capacity (IDMC) who have a close caregiver or legally authorized representative (LAR) may be considered eligible for this study at the treating physician's discretion, provided that the physician is reasonably sure that the possible risks and benefits of the study are clear and that the patient will take the drug as prescribed - Subjects must be diagnosed with a glioma, cholangiocarcinoma or other solid malignant tumor that has progressed despite standard therapy, or for which no effective standard therapy exists, with biopsy-confirmed evidence of an IDH1 or IDH2 mutation associated with neomorphic activity of the encoded proteins; patients must have IDH1 or IDH2 mutation which must be detected in a clinical accredited laboratory using a Food and Drug Administration (FDA)-approved molecular test or a validated deoxyribonucleic acid (DNA)-based assay conducted in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory; only specific mutations that lead to a neomorphic phenotype will be eligible for enrollment, and include IDH1: R132V, R132G, R132S, R132L, R132C and R132H; IDH2: R140W, R140L, R140Q, R172W, R172G, R172S, R172M, R172K - Patients must have tumors determined to be easily accessible for biopsy and must be willing to have serial biopsies (with a third biopsy upon evidence of disease progression); in case of multiple lesions, tumor biopsies will be performed on the most accessible site of disease; all possible precautions to avoid complications will be taken, including discussions in multidisciplinary meetings, if needed; patients affected by glioma will not be considered for study biopsies - Patients must be willing to undergo extra blood sampling for correlative studies - Subjects with extracranial disease must have evaluable disease by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1); subjects affected by glioma must have evaluable disease by Response Assessment in Neuro-Oncology Criteria (RANO) criteria - For subjects with glioma, specific inclusion criteria are as follows: - The disease should be recurrent or transformed glioma; subjects must not have had prior surgery (biopsy allowed) or radiation therapy within 3 weeks of enrollment - There must be an enhancing component of disease, as evaluated on pre-treatment magnetic resonance imaging (MRI) - For patients with World Health Organization (WHO) grade III or IV glioma and progressive disease < 12 weeks after completion of chemoradiotherapy, progression can be defined by the following set of criteria: - New enhancement outside of the radiation field (beyond the high-dose region or 80% isodose line) - If there is unequivocal evidence of viable tumor on histopathologic sampling (e.g., solid tumor areas. --- R132V --- --- R132G --- --- R132S --- --- R132L --- --- R132C --- --- R132H ---

Primary Outcomes

Description: Will be determined by investigator assessment using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) for extracranial solid tumors, Response Assessment in Neuro-Oncology (RANO) criteria for intracranial glioma. Overall response rate and a 90% creditable interval in each cohort will be estimated using the approach described by Koyama. For the other solid tumors cohort, descriptive statistics and graphical displays will be used to summarize results within tumor types.

Measure: Overall response rate

Time: Up to completion of course 8

Secondary Outcomes

Description: For time to event endpoints, Kaplan-Meier curves will be used to demonstrate distributions and median estimates will be reported with 95% confidence intervals. For each cohort, graphical displays such as swimmer plots, will be used to demonstrate patterns of response, progression and death, and in the third cohort they will also indicate disease type.

Measure: Progression-free survival

Time: From start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year

Description: Adverse events will be tabulated by type and grade in each cohort, and also across cohorts.

Measure: Incidence of adverse events

Time: Up to 1 year

Other Outcomes

Description: Absolute and fold changes for exploratory endpoints will be calculated between baseline and each subsequent follow-up time point. These will be displayed graphically versus (vs.) time for each cohort. Differences will be plotted vs. response status. Paired t-tests will be used to evaluate if differences between baseline and each subsequent time point are significant. Summary statistics will be reported (with 95% confidence intervals) to demonstrate mean differences in fold-change (or log fold-change) between responders and non-responders.

Measure: 2HG plasma magnetic resonance spectroscopy (MRS) levels

Time: Baseline up to post-treatment

Description: Absolute and fold changes for exploratory endpoints will be calculated between baseline and each subsequent follow-up time point. These will be displayed graphically vs. time for each cohort. Differences will be plotted vs. response status. Paired t-tests will be used to evaluate if differences between baseline and each subsequent time point are significant. Summary statistics will be reported (with 95% confidence intervals) to demonstrate mean differences in fold-change (or log fold-change) between responders and non-responders.

Measure: 2HG plasma concentration level

Time: Up to 1 year

Description: Will be associated with differential levels of 2HG production, treatment response and resistance. Absolute and fold changes for exploratory endpoints will be calculated between baseline and each subsequent follow-up time point. These will be displayed graphically vs. time for each cohort. Differences will be plotted vs. response status. Paired t-tests will be used to evaluate if differences between baseline and each subsequent time point are significant. Summary statistics will be reported (with 95% confidence intervals) to demonstrate mean differences in fold-change (or log fold-change) between responders and non-responders.

Measure: Co-occurring alterations detected via mass cytometry (cyTOF), ribonucleic acid (RNA) sequencing and/or deoxyribonucleic acid (DNA) sequencing

Time: Baseline up to 1 year

6 The PRIME Trial: PARP Inhibition in IDH Mutant Effectiveness Trial. A Phase II Study of Olaparib in Isocitrate Dehydrogenase (IDH) Mutant Relapsed/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome

This phase II trial studies how well olaparib works in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory), or myelodysplastic syndrome. Patients must also have a change in the gene called the IDH gene (IDH mutation). Olaparib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. This study is being done to see if olaparib is better or worse in treating acute myeloid leukemia or myelodysplastic syndrome compared to the standard chemotherapy drugs.

NCT03953898
Conditions
  1. Acute Myeloid Leukemia
  2. Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
  3. Recurrent Acute Myeloid Leukemia
  4. Recurrent Myelodysplastic Syndrome
  5. Refractory Acute Myeloid Leukemia
  6. Refractory Myelodysplastic Syndrome
  7. Therapy-Related Acute Myeloid Leukemia
Interventions
  1. Drug: Olaparib
MeSH:Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Preleukemia Myelodysplastic Syndromes Syndrome
HPO:Acute megakaryocytic leukemia Acute myeloid leukemia Leukemia Myelodysplasia Myeloid leukemia

Only specific mutations that lead to a neomorphic phenotype will be eligible for enrollment, and include those listed below: - IDH1: R132V, R132G, R132S, R132L, R132C and R132H - IDH2: R140W, R140L, R140Q, R172W, R172G, R172S, R172M, R172K. --- R132V --- --- R132G --- --- R132S --- --- R132L --- --- R132C --- --- R132H ---

Primary Outcomes

Description: The effectiveness of the drug in patients for each cohort will be independently assessed by ORR. The exact two-sided 95% confidence intervals (CI) for the ORR will be reported. The CI based on the Greenwoods variance will be reported.

Measure: Overall response rate (ORR)

Time: Up to 12 months

Description: Will be evaluated by Myelodysplastic Syndrome International Working Group (IWG) 2006 criteria (Cheson et al., 2006) and acute myeloid leukemia (AML) IWG 2003 criteria (Cheson et al., 2003) after 6 cycles of treatment. Cumulative ORR will include complete remission (CR), complete remission with incomplete blood count recovery (CRi), partial response (PR), and bone marrow complete remission (marrow CR) achieved at least at one point during these 6 cycles.

Measure: Cumulative ORR

Time: Up to 6 cycles

Secondary Outcomes

Description: Will be estimated using the Kaplan-Meier method with the 95% CIs. The CI based on the Greenwoods variance will be reported. In addition, the possible risk factors will be compared for survival with log-rank test. For multivariate analysis, the proportional hazards Cox model will be applied to investigate potential prognostic factors, such as age and stage of disease on the survival data. The adjusted p-values of the odds ratios and the adjusted 95% confidence interval will be reported.

Measure: Progression-free survival (PFS)

Time: From first day of therapy to the time of documentation of progression, death of any cause, or last follow-up, whichever comes first, assessed up to 12 months

Description: Will be estimated using the Kaplan-Meier method with the 95% CIs. The CI based on the Greenwoods variance will be reported. In addition, the possible risk factors will be compared for survival with log-rank test. For multivariate analysis, the proportional hazards Cox model will be applied to investigate potential prognostic factors, such as age and stage of disease on the survival data. The adjusted p-values of the odds ratios and the adjusted 95% confidence interval will be reported.

Measure: Overall survival (OS)

Time: From first day of therapy to the time of death or last follow-up, whichever comes first, assessed up to 12 months

Measure: Duration of response (DOR)

Time: From first documentation of response to the time of documentation of progression, death of any cause, or last follow-up, whichever comes first, assessed up to 12 months

Description: Non-hematologic toxicity will be evaluated by Common Terminology Criteria for Adverse Events version 5 criteria.

Measure: Incidence of adverse events

Time: Up to 12 months

Other Outcomes

Description: The Mann-Whitney U test will be used to test for differences in post-treatment plasma 2HG concentrations between patients with a response to treatment and those without. Will also test for differences in Delta2HG (defined as pre-treatment minus post-treatment plasma concentration) between patients with a response to treatment and those without. Differences with p =< 0.05 will be considered significant. The area under the receiver operating characteristic curve (ROC AUC) will be calculated to determine the cutoff value of the Delta2HG difference. The optimal cutoff value will be determined at the point on the ROC curve at (sensitivity + specificity - 1) is maximized.

Measure: Change in 2-hydroxyglutarate (2HG) levels

Time: Up to 12 months

Description: Will define MRD based on the variation of the variant allele frequency of the IDH1/2 mutation in the bone marrow of the patients before and during therapy. Will evaluate two different variables: MRD negativity (defined by the absence of detection of the IDH mutant in the sample) and the molecular response (defined by the log reduction of the frequency of the mutant allele). MRD negativity is a qualitative variable and will be reported as a percentage with 95% confidence interval for each time point and mutation. Will compare the different groups using a Chi-Square test. Molecular response is a quantitative variable reported as a median, min and max for each time point and we will use a student t test for the comparison of the different groups.

Measure: Minimal residual disease (MRD) assessment

Time: Up to 12 months

Description: Will be estimated using Poisson distribution model as the fraction of positive reads divided by total reads containing a target. The limit of detection will be defined for each mutation as the mean value of IDH1/2 wild-type controls plus three standard deviations.

Measure: Mutant allele frequency

Time: Up to 12 months

7 GBM AGILE: Global Adaptive Trial Master Protocol: An International, Seamless Phase II/III Response Adaptive Randomization Platform Trial Designed To Evaluate Multiple Regimens In Newly Diagnosed and Recurrent GBM

Glioblastoma (GBM) adaptive, global, innovative learning environment (GBM AGILE) is an international, seamless Phase II/III response adaptive randomization platform trial designed to evaluate multiple therapies in newly diagnosed (ND) and recurrent GBM.

NCT03970447
Conditions
  1. Glioblastoma
Interventions
  1. Drug: Temozolomide
  2. Drug: Lomustine
  3. Drug: Regorafenib
  4. Radiation: Radiation
MeSH:Glioblastoma
HPO:Glioblastoma multiforme

- Histologically confirmed GBM/gliosarcoma (WHO criteria; non-IDH R132H mutant) at first or second recurrence after initial standard, control or experimental therapy that includes at a minimum Radiation Therapy (RT). --- R132H ---

Primary Outcomes

Description: Overall survival is defined from the time of randomization to death from any cause. Patients still alive at the time of an analysis will be considered censored at their date of last contact.

Measure: Overall Survival (OS)

Time: From date of randomization until the date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.

Secondary Outcomes

Description: Progression-free survival is defined as the time from randomization to clinically determined progression or death from any cause. All participants will be included in the analysis of PFS.

Measure: Progression-free survival (PFS)

Time: From date of randomization to date of clinically determined progression or date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.

Description: Tumor response is categorized by Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD). Response captured from initiation of study treatment until disease progression.

Measure: Tumor Response

Time: From initiation of study treatment to date of disease progression, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.

Description: Duration of response (CR+PR) is defined as time from date of response to date of clinically determined disease progression or death from any cause.

Measure: Duration of Response (CR + PR)

Time: From date of response to date of clinically determined disease progression or date of death from any cause, or until 12 months following last patient randomization (approximately 2 years), whichever comes first.

8 A Phase 3, Multicenter, Randomized, Double-blind, Placebo-Controlled Study of AG-881 in Subjects With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation

Study AG881-C-004 is a phase 3, multicenter, randomized, double-blind, placebo-controlled study comparing the efficacy of AG-881 to placebo in participants with residual or recurrent Grade 2 glioma with an IDH1 or IDH2 mutation who have undergone surgery as their only treatment. Participants will be required to have central confirmation of IDH mutation status prior to randomization. Approximately 366 participants are planned to be randomized 1:1 to receive orally administered AG-881 40 mg QD or placebo.

NCT04164901
Conditions
  1. Grade 2 Glioma
  2. Residual Glioma
  3. Recurrent Glioma
Interventions
  1. Drug: AG-881
  2. Drug: Matching Placebo
MeSH:Glioma
HPO:Glioma

- Have confirmed IDH1 (IDH1 R132H/C/G/S/L mutation variants tested) or IDH2 (IDH2 R172K/M/W/S/G mutation variants tested) gene mutation status disease by central laboratory testing during the Prescreening period and available 1p19q status by local testing (eg, fluorescence in situ hybridization [FISH], comparative genomic hybridization [CGH] array, sequencing) using an accredited laboratory. --- R132H ---

Primary Outcomes

Measure: Progression-Free Survival (PFS)

Time: Up to approximately 30 months

Secondary Outcomes

Measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time: Up to approximately 30 months

Measure: Tumor Growth Rate as Assessed by Volume

Time: Up to approximately 30 months

Measure: Time to Next Intervention

Time: Up to approximately 5 years

Measure: Objective Response Rate

Time: Up to approximately 30 months

Measure: Time to Response

Time: Up to approximately 30 months

Measure: Duration of Response

Time: Up to approximately 30 months

Measure: Overall Survival

Time: Up to approximately 5 years

Description: The FACT-Br is a participant-reported measure designed to assess the quality of life for participants with brain tumors. The FACT-Br is a measure comprising the following subscales: Physical Well-Being, Functional Well-Being, Emotional Well-Being, and Social Well-Being subscales from the FACT-G, with the addition of a brain tumor- specific subscale.

Measure: Health-Related Quality of Life as Measured by Functional Assessment of Cancer Therapy-Brain Questionnaire (FACT-Br)

Time: Up to approximately 30 months

Measure: Progression-Free Survival (PFS) as Assessed by the Investigator

Time: Up to approximately 30 months

Measure: Maximum Observed Serum Concentration (Cmax) of AG-881

Time: Days 1 and 15 of Cycle 1(predose and multiple timepoints up to 4 hours postdose), Day 1 of Cycle 2(predose and multiple time points up to 4 hours postdose), Predose on Day 1 of every cycle thereafter(each cycle is 28 days), and within 7 days of last dose

Measure: Area Under Concentration Time Curve from Time 0 to Tau (AUC0-tau) of AG-881

Time: Days 1 and 15 of Cycle 1(predose and multiple timepoints up to 4 hours postdose), Day 1 of Cycle 2(predose and multiple time points up to 4 hours postdose), Predose on Day 1 of every cycle thereafter(each cycle is 28 days), and within 7 days of last dose

Measure: Time to Reach Maximum Serum Concentration (Tmax) of AG-881

Time: Days 1 and 15 of Cycle 1(predose and multiple timepoints up to 4 hours postdose), Day 1 of Cycle 2(predose and multiple time points up to 4 hours postdose), Predose on Day 1 of every cycle thereafter(each cycle is 28 days), and within 7 days of last dose

9 Non Invasive IDentification of Gliomas With IDH1 Mutation by Free Plasmatic DNA Analysis, 2-hydroxyglutarate Dosage in the Urines and 2-hydroxyglutarate Detection by Brain SPEctro-MRI: Diagnostic and Follow-up Application (IDASPE)

The recurrent mutation IDH1Arg132His leads to the cellular accumulation of D-2-hydroxyglutarate (2-HG), thus representing a diagnostic marker (this change is almost specific for gliomas) and prognostic (mutated gliomas have longer survival) of interest. The main objective is to identify the patients with IDH1 mutated glioma by three complementary approaches -genetic (identification of IDH1 mutation in plasmatic DNA), biochemical (2-HG dosage in the urine of patients) and radiological (2-HG

NCT01703962
Conditions
  1. Non Invasive Diagnosis of Glioma
MeSH:Glioma
HPO:Glioma

The main objective is to identify the patients with IDH1 mutated glioma by three complementary approaches -genetic (identification of IDH1 mutation in plasmatic DNA), biochemical (2-HG dosage in the urine of patients) and radiological (2-HG Inclusion Criteria: Inclusion Criteria - Affiliated to Health Insurance regimen (sécurité sociale) - Patient of 18 years or more - written informed consent - Glioma grade II or III histologically proven - Frozen samples available - Known status IDH1/IDH2 - Presence of a measurable residual tumor (> 2 cm in diameter FLAIR) - Karnofsky Performance Status (KPS)> 60 Exclusion Criteria: - Contraindication to MRI * - The rare patients with IDH2 mutation or with non Arg132His IDH1 mutation will be excluded - Inability to provide informed consent - Patient under guardianship or deprived of liberty by court Inclusion Criteria: Inclusion Criteria - Affiliated to Health Insurance regimen (sécurité sociale) - Patient of 18 years or more - written informed consent - Glioma grade II or III histologically proven - Frozen samples available - Known status IDH1/IDH2 - Presence of a measurable residual tumor (> 2 cm in diameter FLAIR) - Karnofsky Performance Status (KPS)> 60 Exclusion Criteria: - Contraindication to MRI * - The rare patients with IDH2 mutation or with non Arg132His IDH1 mutation will be excluded - Inability to provide informed consent - Patient under guardianship or deprived of liberty by court Non Invasive Diagnosis of Glioma Glioma Our preliminary results indicate an extremely high amount of D-2HG in gliomas and CSF of the patients, and therefore the possibility to detect its presence by spectro-MRI, and to establish a non-invasive diagnosis of glioma with IDH1 mutation. --- Arg132His ---

The main objective is to identify the patients with IDH1 mutated glioma by three complementary approaches -genetic (identification of IDH1 mutation in plasmatic DNA), biochemical (2-HG dosage in the urine of patients) and radiological (2-HG Inclusion Criteria: Inclusion Criteria - Affiliated to Health Insurance regimen (sécurité sociale) - Patient of 18 years or more - written informed consent - Glioma grade II or III histologically proven - Frozen samples available - Known status IDH1/IDH2 - Presence of a measurable residual tumor (> 2 cm in diameter FLAIR) - Karnofsky Performance Status (KPS)> 60 Exclusion Criteria: - Contraindication to MRI * - The rare patients with IDH2 mutation or with non Arg132His IDH1 mutation will be excluded - Inability to provide informed consent - Patient under guardianship or deprived of liberty by court Inclusion Criteria: Inclusion Criteria - Affiliated to Health Insurance regimen (sécurité sociale) - Patient of 18 years or more - written informed consent - Glioma grade II or III histologically proven - Frozen samples available - Known status IDH1/IDH2 - Presence of a measurable residual tumor (> 2 cm in diameter FLAIR) - Karnofsky Performance Status (KPS)> 60 Exclusion Criteria: - Contraindication to MRI * - The rare patients with IDH2 mutation or with non Arg132His IDH1 mutation will be excluded - Inability to provide informed consent - Patient under guardianship or deprived of liberty by court Non Invasive Diagnosis of Glioma Glioma Our preliminary results indicate an extremely high amount of D-2HG in gliomas and CSF of the patients, and therefore the possibility to detect its presence by spectro-MRI, and to establish a non-invasive diagnosis of glioma with IDH1 mutation. --- Arg132His --- --- Arg132His ---


10 Pembrolizumab for Newly Diagnosed Glioblastoma: a Prospective, Open-label, Single-arm, Multicenter Phase II Study

The study explores the addition of pembrolizumab to temozolomide-based radiotherapy in patients with newly diagnosed glioblastoma.

NCT03899857
Conditions
  1. Newly Diagnosed Glioblastoma
Interventions
  1. Drug: Pembrolizumab
MeSH:Glioblastoma
HPO:Glioblastoma multiforme

- Newly diagnosed glioblastoma or gliosarcoma as confirmed by local histopathology - The patient is at least 18 years of age on day of signing informed consent - Absence of isocitrate dehydrogenase (IDH)1 R132H mutation by immunohistochemistry - A maximum dose of 4 mg/day dexamethasone or equivalent doses for other corticosteroids, which has been stable or decreased for ≥5 days prior to start of radiotherapy - Patient who are treated with anticoagulants are on a stable dose for at least two weeks prior to start of radiotherapy (RT) - The patient is male or a non-pregnant, non-lactating female - Females of childbearing potential must have a negative beta-human chorionic gonadotropin (HCG) pregnancy test within 2 weeks prior to receiving the first dose of study medication. --- R132H ---

Primary Outcomes

Description: To explore whether the addition of pembrolizumab to standard temozolomide-based radiochemotherapy improves the outcome of newly diagnosed glioblastoma or gliosarcoma patients, determined by the overall survival rate at 12 months

Measure: Overall survival at 12 months

Time: At 12 months

Secondary Outcomes

Measure: Response rates using (i)RANO (immunotherapy response assessment in neuro-oncology) criteria

Time: From the inclusion in the study until the end of follow-up (up to approximately 36 months)

Measure: Progression-free survival (PFS) at 6 and 12 months

Time: At 6 and 12 months

Measure: Time to treatment failure (TTF)

Time: From the inclusion in the study until the end of follow-up (up to approximately 36 months)

Description: HRQoL will be assessed with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) version 3. Scoring: 0 to 100. Higher scores mean a better level of functioning.

Measure: Health-related Quality of life (HRQol)

Time: From the inclusion in the study until the end of follow-up (up to approximately 36 months)

Description: Expression levels of PD-L1 will be determined in the tumor tissue and correlated with response as determined by MRI and progression-free as well as overall survival

Measure: Correlation of programmed cell death (PD-1) ligand 1 (PD-L1) expression levels with response to treatment and outcome

Time: From the inclusion in the study until the end of follow-up (up to approximately 36 months)

11 A Randomized Phase II/III Open-Label Study of Ipilimumab and Nivolumab Versus Temozolomide in Patients With Newly Diagnosed MGMT (Tumor O-6-Methylguanine DNA Methyltransferase) Unmethylated Glioblastoma

This phase II/III trial compares the usual treatment with radiation therapy and temozolomide to radiation therapy plus immunotherapy with ipilimumab and nivolumab in treating patients with newly diagnosed MGMT unmethylated glioblastoma. Radiation therapy uses high energy photons to kill tumor and shrink tumors. Chemotherapy drugs, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving radiation therapy with ipilimumab and nivolumab lengthen the time without brain tumor from returning or growing and extend patients life compared to usual treatment of radiation therapy and chemotherapy.

NCT04396860
Conditions
  1. Gliosarcoma
  2. MGMT-Unmethylated Glioblastoma
Interventions
  1. Biological: Ipilimumab
  2. Biological: Nivolumab
  3. Device: NovoTTF-100A Device
  4. Other: Quality-of-Life Assessment
  5. Other: Questionnaire Administration
  6. Radiation: Radiation Therapy
  7. Drug: Temozolomide
MeSH:Glioblastoma Gliosarcoma
HPO:Glioblastoma multiforme

Note: Patients with tissue that is insufficient or inadequate for analysis, fails MGMT testing, or has indeterminate or methylated MGMT promoter are excluded - IDH mutation testing by at least one method (such as immunohistochemistry for IDH1 R132H) must be performed as part of standard of care and no mutation must be found (i.e IDH wildtype). --- R132H ---

Primary Outcomes

Description: PFS will be defined as time from randomization to disease progress or death. This analysis will be performed on the intent-to-treat basis. PFS distributions for each treatment group will be estimated via the Kaplan-Meier survival function. Will utilize the "PFS resolution" guidance provided in the ALLIANCE A071102 study, the updated Response Assessment in Neuro-Oncology Criteria (RANO) criteria.

Measure: Progression-free survival (PFS) (Phase II)

Time: From randomization to disease progress or death, assessed up to 4 years

Description: OS will be defined as time from randomization to death from any cause. Will be performed on the intent-to-treat basis. Overall survival distributions for each treatment group will be estimated via the Kaplan-Meier survival function.

Measure: Overall survival (OS) (Phase III)

Time: From randomization to death from any cause, assessed up to 4 years

Secondary Outcomes

Description: PFS curves will be estimated via the Kaplan-Meier method and a stratified log-rank test.

Measure: PFS for the entire cohort (Phase II/III)

Time: At 2 year

Description: 2-year OS will be compared between treatment arms, to determine whether the proportion surviving to this landmark is increased in the experimental (ipilimumab [ipi] + nivolumab [nivo]) arm. Estimates will be obtained from the Kaplan Meier curves, and a test comparing the proportion surviving with an appropriate variance term that accounts for censoring (Greenwood's formula) will be used.

Measure: OS proportion

Time: At 2 years

Description: Adverse events (AEs) will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 and Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE).

Measure: Comparative frequency of specific adverse events of interest

Time: Up to 4 years

Description: Adverse events will be graded according to CTCAE v5.0 and PRO-CTCAE. Comprehensive summaries of all AEs by treatment arm will be generated and examined. Counts and frequencies of worst (highest score) AE per patient will be presented overall and by AE type category, separately by assigned treatment group. Complementing physician-assessed AEs will be selected PRO-CTCAE symptom items that have demonstrated sensitivity to immunotherapy-related toxicities but do not overlap with MDASI-BT. The following PRO-CTCAE symptom items will be monitored: rash, itching, muscle pain, joint pain, headache, chills, mouth/throat sores, skin dryness, hair loss, cough, taste changes, dizziness, swelling, hot flashes.

Measure: Frequency summaries for all adverse event types

Time: Up to 4 years

Description: Will be assessed using the MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT)-modified. The MDASI-BT consists of 23 symptoms rated on an 11-point ordinal scale (0 to 10) to indicate the presence and severity of the symptom in the last 24 hours, with 0 being "not present" and 10 being "as bad as you can imagine." These interference items include: general activity, mood, work (includes both work outside the home and housework), relations with other people, walking, and enjoyment of life. Complementing MDASI-BT will be selected PRO-CTCAE symptom items that have demonstrated sensitivity to immunotherapy-related toxicities but do not overlap with MDASI-BT.

Measure: Patient reported symptom burden

Time: Up to 4 years

Measure: Neurocognitive function (NCF)

Time: Up to 4 years

Description: Will utilize the PRO-CTCAE to assess the following items: abdominal pain, rash, itching, muscle pain, joint pain, pain and swelling at injection site, headache, chills, mouth/throat sores, skin dryness, hair loss, cough, taste changes, dizziness, swelling, and hot flashes.

Measure: Patient-reported toxicity outcomes

Time: Up to 4 years

Other Outcomes

Measure: OS (if the study discontinues in phase II)

Time: At the end of phase II of study

Description: Will assess PD-L1 expression and mutational burden expression specifically.

Measure: Tumor biomarker analyses

Time: Up to 4 years

Description: Will assess the prognostic value of MGMT protein expression (in terms of predicting clinical outcomes such as PFS, OS, and 2-year OS rate) in the two treatment arms, separately. In addition, will evaluate if MGMT protein expression may be predictive of differential treatment effects between the two treatment arms. Correlation methods and survival modeling will be used to address these questions.

Measure: MGMT protein expression

Time: Up to 4 years

12 A Phase II, Open-label Study of ONC201 in Adults With Recurrent High-grade Glioma

The primary objective of this phase II trial is to determine the efficacy and safety of ONC201, an oral small molecule imipridone DRD2 antagonist, in adult subjects with recurrent high-grade glioma. This study will test the research hypothesis that histone H3 K27M mutation sensitizes to oral administration of ONC201 in gliomas.

NCT03295396
Conditions
  1. Glioma
Interventions
  1. Drug: ONC201
MeSH:Glioma
HPO:Glioma

Tumors with known IDH1 (isocitrate dehydrogenase 1) or known IDH2 mutations as determined by immunohistochemistry for the IDH1 R132H variant or by direct sequencing. --- R132H ---

Primary Outcomes

Description: Best overall response rate by RANO

Measure: Overall response rate

Time: Through study completion, an average of 1 year


HPO Nodes


HP:0002664: Neoplasm
Genes 1522
SF3B1 GFI1B IGF2 FIBP RPS7 WT1 COL7A1 TREX1 HSPG2 CASP8 SLC22A18 MC1R TFE3 KRAS PLAG1 OFD1 BRAF NUMA1 KRT16 PSENEN CTPS1 APC SOX9 FANCM OPCML CDKN2A RPS15A CTNNB1 SDHD EDN3 FCN3 NELFA GJC2 MALT1 HPGD GLI1 CD70 SPINK1 LETM1 PMS1 LRP5 HNF1B EXT1 TCF4 ELMO2 MET ANTXR1 KRT16 KRT10 PAX4 SETBP1 TERT WT1 SMARCB1 GJB6 HRAS STK11 BUB1B GNPTAB MYD88 MCC GJB2 BRCA1 TP63 PDGFRL TARS1 NF1 FGFR3 KARS1 BARD1 BRIP1 GATA2 IL1RN BRAF CD81 TNFRSF13B TYROBP AR LIG4 KLF11 ABL1 MVK BMPR1A PIK3CA B3GALT6 SLC37A4 SOS1 TSC1 FGFR3 ATRX FANCG TET2 KIT SRP72 MPL TP53 SMAD4 EVC2 MAPRE2 DLST BRCA1 DICER1 HRAS AKT1 RNR1 TSC1 TNPO3 XRCC4 DNMT3A NEUROD1 THPO MN1 NOD2 SRSF2 PPM1D FLT4 ATP7A IL7 KRAS GDNF WNT10A EPAS1 COL1A1 IL1B MRAP ADAMTS3 PRKCD SUFU PTCH1 ERCC3 KRT14 CXCR4 HOXD13 IGF2 LIG4 PALB2 BLM NRAS ERCC3 FOXP1 SDHD TP53 PKD2 PDX1 TINF2 ADA2 MYF6 RHBDF2 POU6F2 PHKG2 CDKN2A RUNX1 ERCC2 MAP2K2 WT1 USB1 GATA4 FGFR2 ACD CR2 MUTYH ARL6IP6 FAH MSH2 RASA1 NEK1 SOX6 NR0B1 LIG4 CDKN2B NF1 NF1 POLE RPL35 SRY SDHAF2 FANCL CPLX1 FAS PRKAR1A PHB SDHA CALR PIK3R1 FAN1 TET2 TMEM216 RSPO1 SEMA3D MDM4 SDHD HRAS NUP214 GJA1 PIK3CA CCND1 RNF6 MSH2 C11ORF95 MVK MCM4 FLI1 TINF2 KIAA0753 ECM1 ARSA ERCC2 SOX2 SDHC SLC26A2 MPL VANGL1 PUF60 RAD51D POT1 CR2 ESCO2 FOXE1 PMVK SRY GJB4 TRIM37 KIT EXT2 PDGFB KIF1B FANCF IGF2R MLH1 GDNF PIK3CA ASCC1 ASCL1 TCIRG1 APPL1 RPS19 BCL10 IGF2 NRAS FLT3 STAT1 BCL10 RMRP GNAI3 KRAS GPR101 BAP1 NKX2-1 MAX BMPR1A DDB2 SMARCB1 RAD51 FGFR3 ALX4 BTK MSH6 NOTCH3 DICER1 CXCR4 CCBE1 RET WT1 TP53 PALLD RNASEH2B WT1 ATR CCND1 KCNQ1OT1 SMAD4 AHCY STK11 FANCC TRNK BCL6 SMAD4 SKIV2L HMBS TP53 TERT PHOX2B SNAI2 BRAF TCOF1 FANCI NRAS REST SDHC HBB HFE CREBBP MET SEC23A CEP57 CTLA4 TRIM28 SMAD7 GNAS BRCA2 PALB2 FGF8 SBDS RET ALK GJB2 CPLANE1 GPC3 TCTN3 PTEN RB1 INTU CYP26C1 LEMD3 PRLR CDON NLRP1 GPR101 DHH HNF4A MMEL1 DNASE1L3 RASGRP1 ATRX CHEK2 FANCA SPRED1 DNM2 FLT4 CHEK2 RPS19 KLLN HACE1 HNF1A PTPN11 CDKN1B GAS1 BRCA2 KCNQ1OT1 NPM1 FGFR3 MC1R MINPP1 PTPN11 TSC2 ABCA5 BRCA2 PLCB4 SCN11A HNF1A BRAF RB1 CBL ARHGAP26 SUFU PTPRJ C1S APC IRF5 GNAQ GDNF TERT MYSM1 XPC TMC8 COL4A5 ERBB3 SLC26A4 CD96 NSUN2 PDGFRA FERMT1 TYR DNAJC21 MSH2 SH3GL1 TUBB RET BRAF ESR1 PAX3 RHBDF2 RTL1 WRN DYNC2LI1 ELANE EXOC6B RPS26 EWSR1 VHL PIGA GCGR POU6F2 RNF43 POLE BRAF MNX1 SFTPA2 CDH23 ASCL1 APC ACVR1 PIGL BAX RAG2 RSPO1 MSH3 PGM3 FGF3 FANCE MPL TP53 COL7A1 BUB1 TET2 PALB2 ACTB PNP SDHC EDN3 XPA TMC6 NEK1 GNA11 KAT6B KRT1 RUNX1 PAX7 NOTCH1 ENG CTNNB1 ETV6 MPLKIP PARN CDKN2A PTPN3 STAG3 MDM2 TP53 LAMC2 NBEAL2 VAMP7 GNA14 DCLRE1C CBL GCDH FANCC AXIN2 PYGL SOS1 BLK WRAP53 IDH1 KRAS CCM2 APC ASXL1 ATP7B ERCC3 SF3B1 EP300 BRCA2 MGAT2 NRTN CDKN2A DICER1 PMS1 RPS10 TBC1D24 FAH BRCA2 ASXL1 BCR C2CD3 KRAS IDH1 IGLL1 RASA1 BRCA2 CHEK2 PTCH1 RNF113A BRAF MBTPS2 EDNRB IGHM PDGFRB RAF1 MEN1 FASLG TUBB NDUFAF6 FOXI1 TGFBR1 EPCAM CYLD SDHB APC CYP2D6 TAF1 KRT17 BRCA1 BUB1B BAP1 GDF2 BUB1B ERCC2 TP53 KRT5 GATA2 BRCA1 RAD54B MRE11 STAC3 DNMT3A MLH1 BCHE EDN3 CDKN1B AURKA NRAS FLCN IDH2 EDN1 ESCO2 USF3 IGH POT1 ACVRL1 JAK2 NBN NRAS SQSTM1 TMEM127 ZFPM2 SLC12A3 NTHL1 ADA CHIC2 STAT3 SETBP1 FANCB FIBP STAT3 STK11 MLLT10 SFTPC HDAC4 NUP214 GLI2 SLX4 TSC1 ERCC6 TP53 CLCNKB KLF6 OGG1 JAK2 PAX6 RECQL4 RPL31 MYO1H FH RPGRIP1L SLC45A2 RPL10 RPL10 HMBS GDF5 TNFRSF10B PIK3CA GABRD TP53 BRCA2 SEMA4A BCR PALB2 ASXL1 KRT6B CCDC22 SAMD9 DMPK DCC ERCC5 RPL5 CTNNB1 RPS27 TRNS2 PTCH1 PTEN TFAP2A RPS24 RPL35A RET AXIN1 HNF1B ARMC5 UBE2T SRP54 SSX2 DKC1 ERCC3 JAK2 GNA11 LAMB3 GJB2 NFKB1 KCNQ1 GLI3 PIK3CA KANSL1 CASP8 MYC RECQL4 ACAN CACNA1S BDNF KIF11 MDH2 MSL3 FGFR1 TERF2IP HFE NFKB2 TOP2A GFI1 SRD5A3 PHKA2 MAX POLE MAP2K1 EYA1 RNF43 ALX3 SETD2 ERCC4 CTLA4 SIX3 LEMD3 OCRL CDH23 DZIP1L MSH3 AR CDC73 PDGFRL TWIST1 POU2AF1 DKC1 CALR LIN28B KRT6A GATA1 MC1R DIS3L2 CD28 CDC73 ADA2 UROD CIB1 TSR2 WNT5A TET2 PHOX2B BMPER KIT DLC1 MSTO1 H19-ICR SLC25A13 ADAR TMEM67 BMPR1A MLH3 POLR1C KRT6B FH EFL1 TERC BUB3 FOXC2 NOTCH3 KIT NSD1 FGFR2 SLC6A17 MAP3K1 TRIP13 MEG3 RRAS2 BMPR1A NF1 DPM1 LIG4 PARN RHOH BRCA2 NF1 TAF15 RFWD3 VHL H19 BCR KRAS VANGL2 KRAS SDHD DVL3 BIN1 ABL1 GPC3 HAX1 FANCA GDNF NHP2 IGF2 VHL CCL2 EXTL3 RUNX1 PRKCD BLNK MSH6 SLC22A18 IL2RG PTH1R SDHB AIP WDPCP APC KCNJ10 ASPSCR1 OCA2 TP53 WT1 SPRTN TET2 TAL1 L2HGDH KIT SDHC ERCC4 GPR143 PRKN SMAD4 SEMA3C TRNS1 BRCA1 SHOX PCNA FANCG CREB1 TRNH VHL MYLK BAP1 SUFU ANTXR1 POLD1 NODAL IGH JAK2 MS4A1 MEN1 TSC2 GATA2 DHCR7 TINF2 F13B RB1 COL7A1 SCN4A BMPR1A DDB2 CDKN2A SDHD CYP11B2 IL7 ARID1B KIT FGFR1 RET CDKN2A LAMA3 CHEK2 TBX2 TBX18 HNF4A GPC4 SHH LMNA BMP2 YY1 AKT1 WT1 BAP1 FZD2 SH2B3 BTK GATA1 RAD54L ATM CTBP1 PTEN SRY RYR1 CTHRC1 MFN2 PTEN RAD21 PTEN MYC SLC26A2 TP53 CTNNB1 RAD51C NAB2 NLRP1 SUFU DLL1 PSAP SDHB REST TGFBR2 TRIP13 IGH ABCC8 IL6 CPLANE1 H19 FANCD2 FGFR2 RET PKD1 DNMT3A REST CHEK2 GNAQ MXI1 BRIP1 DYNC2LI1 GNAS TP53 GLI3 DIS3L2 NRAS PICALM WT1 BAP1 MEN1 TXNRD2 MGMT PTEN MYD88 GNAS POT1 AGGF1 BUB1 PTEN PORCN HFE NUTM1 PHOX2B MSX2 PMS2 SLX4 H19 USP9X RPL27 GNAS SEC23B CBL CD28 PKHD1 AXIN2 TRPV3 KLLN SSX1 TSC1 PPOX KRT17 CARD14 HRAS TCF3 RPL11 CC2D2A GREM1 CHEK2 AP2S1 NRAS TRNL1 ALX1 CREBBP TCTN3 TET2 ESCO2 DOCK8 NRAS STK11 GCM2 TTC37 WT1 SMAD4 DAXX MITF BCL2 DIS3L2 POLR1D TDGF1 KRAS TNFRSF13C KIT PHOX2B SF3B1 RPL15 NF1 TERT TNFRSF1B FANCD2 MLH3 IL7R GPC4 H19-ICR SLC17A9 MEN1 MST1R KIT RAD50 TJP2 DNAJC21 PDCD10 MUTYH IL12RB1 SH2D1A FGFR2 NBN KRAS KIT CASR ENPP1 SDHB HRAS IKBKG PNP EXT2 BRD4 SMARCB1 REST COL11A2 TG KIT LIG4 SUFU NBN RSPRY1 CYSLTR2 SDHD AAGAB BLM RAG1 RNF139 RB1CC1 ACD PTPN11 SLC26A2 TREX1 BMPR1B DDR2 ZAP70 MNX1 MAGT1 AIP GATA2 AR STAR IFIH1 IDH2 BRCA1 USP8 RB1 FGFRL1 SMO USP8 RMRP SLC25A11 MLH3 FUZ DOCK8 SUFU NF2 KDR KRAS RPS14 CASP10 SRP54 ZSWIM6 TBXT PTCH2 EWSR1 TNFRSF13C MTAP NQO2 RPL18 DNAJC21 GCK ERCC6 KDM6B EXT1 SBDS CCND1 SDHAF2 KCNH1 CYLD LMOD1 PDGFRA CAT CHRNG TRNQ ADA NRAS TLR2 SHOX FGFR3 BCL10 TYR KRAS COL2A1 PTCH2 SMO GBA MSTO1 TREM2 JAK2 TMEM231 MSH2 ASXL1 RET DHCR7 NBN PIK3CA NSD2 SDHB EIF2AK4 PALB2 KIF7 PTPN11 PIK3CA HLA-DRB1 STIM1 TMC6 KIF1B TNFSF15 RELA AKT1 NPM1 APC SDHA SDHB STAT6 CDKN1C CDC73 PTCH2 KANSL1 ZSWIM6 FLCN HBB LZTS1 FN1 TRAF7 ACP5 CTNNB1 MLH1 EXT2 RNASEL RNASEH2A IL2RG ATP7A CDK4 CYP11B1 MMP1 SDHB ATRX ACTG2 FOXH1 OFD1 NEK9 STS MUC5B PRKCD PTPN11 PTCH2 LRRC8A RPL26 MSH6 NNT LZTR1 CDC73 PTEN AKT1 AKT1 SASH1 HRAS ANAPC1 PTPN12 KCNJ11 TCF4 GATA2 MLH3 ERCC4 GNB1 DISP1 IDH1 BCR GANAB MSH6 NR5A1 TSC2 GFI1 TNFSF12 TRNP MAPK1 IFNG FLT4 MTM1 WWOX HABP2 RPS28 HRAS SLCO2A1 ND5 SDHB CHD7 BRIP1 SLC37A4 MC2R XRCC3 TNFRSF4 NAGS PHF21A ZIC2 PCGF2 SMARCE1 CTNNB1 SRP54 CDH1 CDK4 RPS20 KCNJ10 RAD21 RNF6 COL14A1 SMO CD19 WRN SRGAP1 CDKN2C AXIN2 GPC6 WWOX HSPA9 FOXI1 CPOX RPS17 APC2 MYH8 SERPINA1 ATM LMX1B ENG POLH TGFBR2 DHX37 VEGFC KIF1B KRT17 DDX41 SPIB CBFB HRAS BCL10 PIGL FGFR1 NSD1 F5 KCNN3 BAX PIEZO2 RECQL4 CREBBP KIT PDGFB PDE6D ABCA5 AKT1 KLHDC8B TNFSF12 EPCAM RARA MLH1 GINS1 EVC PIK3CA FANCE WIPF1 NF2 PDGFRA PRKAR1A CDH1 SDHD PRCC TRNF PTCH1 TNFRSF1B WNT10A WWOX MAD1L1 MTOR WDPCP RNASEH2C NSD2 SAMD9L FH LPP NF1 KRIT1 NTHL1 IL12A HNF1A CDH1 SMARCB1 SMARCE1 CD19 FH FDPS TRPS1 ERCC4 SMPD1 SMARCD2 BRCA1 MPL CRKL SEC23A EXT1 PERP ATM FOXE1 CDKN2B CTSC SIX1 FAM149B1 CDH1 RAD51C ALX3 DLST TRIP13 ING1 PDGFRB FLT3 COL18A1 MST1 TGIF1 TMEM107 SRSF2 TRIM28 BAP1 ANTXR2 CD79A PIK3R1 MAP3K1 NOP10 PIK3CA POLD1 KDSR CCND1 TP53 TMC8 ALK MAP2K1 CD79B SDHC ECE1 PALLD CTSA PRDM16 IVNS1ABP CALR FLNA GPR101 BRCA2 ERCC2 DYNC2H1 TFAP2A COL2A1 DVL1 TERT APC TERT TEK EXT2 TERC ALX4 OFD1 LMO1 PDGFRB RPS14 DCC RTEL1 INS TSC2 FAM20C MYH11 GPC3 SCN9A SMAD4 RASGRP1 HBB TGFBR2 RERE NDP PLA2G2A TCF4 MAD2L2 SKI AIP HMMR SDHC SNAI2 PIK3CA LMNA PGM3 ABCB11 TAL2 WT1 VHL PIK3CA TCTN3 SAMD9L ICOS GLI3 RB1 SLC25A13 SDHC DCLRE1C GCM2 VANGL1 SIX6 WT1 PMS2 KCNH1 BARD1 H19-ICR GNAS TERT CIB1 B3GALT6 GJB3 ERBB2 SDHA KRAS CDC73 TNFRSF13B TET2 FGFR3 WAS SEC23B TGFBR2 TP53 NF2 SMARCA4 NF2 SLC26A4 ANTXR2 WRAP53 FAS SAMHD1 TP53 TET2 ATP7A PTEN SH3KBP1 CARMIL2 MVD PDGFB ABCC6 G6PC1 TRNK KRAS GPC3 PTEN NF2 JAK2 DMRT3 GNAQ RAD51 GTF2H5 TMEM127 TERT RUNX1 FAT4 AR HABP2 NR4A3 EP300 MINPP1 OFD1 RASA1 DLEC1 BIRC3 AIP CD27 PHOX2B BMPR1A KCNE3 PLCD1 RAD51 KRT1 MSH3 MITF EPHB2 DHCR24 RABL3 KRT17 XRCC2 NRAS ITK VHL BICC1 RECQL4 SMARCAD1 MYCN RET CTC1 PTCH1 JAK2 SRC SDHB PHOX2B AKT1 KEAP1 JAG1 VHL LETM1 NLRP1 MEN1 BRCA2 FLCN C2CD3 RFWD3 XPA APC APC SDHD FOXO1 MAFA WHCR GPC4 MLH1 ICOS CDKN1B MTMR14 KIT DICER1 EP300 ZFHX3 MMP1 PRKAR1A KRT9 F13A1 CTNNB1 MPL INPP5E NF1 DKC1 TERT DLK1 SCN10A STS RPS29 PTEN FLCN LRBA ELANE GTF2E2 ATM PIK3CA GPR35 CYLD RAD51C CDKN1A WT1 DICER1 PIK3CA TERC PIK3CA SLC25A11 GNAS CEBPA ATP6V1B2 RET XPC EXT1 BRCA2 SH2B3 ERCC3 BRCA2 RTEL1 WASHC5 ERCC2 AKT1 KCNAB2 CYLD STK4 POLH ERCC5 CDH1 CEL XIAP MSR1 TP53 TET2 DHH PRKAR1A