There are 11 clinical trials

Clinical Trials

1 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 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 ---

2 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 Glioblastoma Diffuse Midline Glioma H3 K27M Glioma Thalamic Glioma Infratentorial Glioma Basal Ganglia Glioma 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 ---

3 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 Glioblastoma Drug: Temozolomide Drug: Neratinib Drug: CC-115 Drug: Abemaciclib

MeSH:Glioblastoma

HPO:Glioblastoma multiforme

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

4 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 Advanced Malignant Solid Neoplasm Glioblastoma Recurrent Cholangiocarcinoma Recurrent Glioma Recurrent Malignant Solid Neoplasm WHO Grade II Glioma WHO Grade III Glioma Drug: Olaparib

MeSH:Glioblastoma Glioma Cholangiocarcinoma Neoplasms

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 ---

5 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 Glioma 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 ---

6 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 Glioma Drug: AG-120 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 ---

7 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 Newly Diagnosed Glioblastoma 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 ---

8 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 Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome IDH1 NP_005887.2:p.R132H IDH2 NP_002159.2:p.R140X Myelodysplastic Syndrome Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia Therapy-Related Acute Myeloid Leukemia 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 ---

9 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 Glioblastoma Drug: Temozolomide Drug: Lomustine Drug: Regorafenib 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 ---

10 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 Grade 2 Glioma Residual Glioma Recurrent Glioma Drug: AG-881 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 ---

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 Gliosarcoma MGMT-Unmethylated Glioblastoma Biological: Ipilimumab Biological: Nivolumab Device: NovoTTF-100A Device Other: Quality-of-Life Assessment Other: Questionnaire Administration Radiation: Radiation Therapy 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 ---

HPO Nodes