SNPMiner Trials (Home Page)
Report for Mutation Y537S
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 5 clinical trials
Clinical Trials
1 An Open-Label, Single Arm, Phase II Trial to Evaluate the Efficacy of 500mg Fulvestrant (Faslodex) in ESR1 Mutated Postmenopausal Women With Hormone Receptor Positive, HER2 Negative Locally Advanced or Metastatic Breast Cancer After Previous Aromatase Inhibitor Treatment
This is an open-label, single arm, phase II trial to evaluate the efficacy and safety of 500mg Fulvestrant (Faslodex®) in ESR1 mutated postmenopausal women with hormone receptor positive, HER2 negative locally advanced or metastatic breast cancer after previous aromatase inhibitor therapy. Fifty patients will be enrolled and treated with 500 mg Fulvestrant until disease progression or study closed. Treatment will continue until disease progression, unless any of the criteria for treatment discontinuation are met first. If a patient progresses during the treatment period, the patient must be withdrawn from the treatment and further treatment will be at the investigator's discretion.
NCT03202862 Breast Neoplasms Drug: Fulvestrant MeSH:Breast Neoplasms
HPO:Breast carcinoma Neoplasm of the breast
The blood sample is clarified to be ESR1 mutated, The mutation should be: Y537C, Y537N, Y537S, S463P and D538G. --- Y537C --- --- Y537N --- --- Y537S ---
Primary Outcomes
Description: The study will be closed at all the patients progressed or 12 months after the last patient has been recruited depends on which one met first. From date of the first recruitment until the date of all the patients progressed or 12 months after the last patient has been recruited, whichever came first, assessed up to 10 years.
Measure: Tumour assessment Time: An average of 5 years, up to 10 years.2 An Open-Label, Randomized, Multicenter Study Evaluating the Activity of Lasofoxifene Relative to Fulvestrant for the Treatment of Pre- and Postmenopausal Women With Locally Advanced or Metastatic ER+/HER2− Breast Cancer With an ESR1 Mutation
This is an open label, randomized, multicenter study evaluating the activity of lasofoxifene relative to fulvestrant for the treatment of pre- and postmenopausal women with locally advanced or metastatic ER+/HER2− breast cancer with an acquired ESR1 mutation and who have disease progression on an aromatase inhibitor (AI) in combination with a cyclin dependent kinase (CDK) 4/6 inhibitor. The primary objective is to evaluate the progression free survival (PFS) of 5 mg lasofoxifene relative to fulvestrant for the treatment of pre- and postmenopausal women with locally advanced or metastatic estrogen receptor positive (ER+)/human epidermal growth factor 2 negative (HER2−) breast cancer with an estrogen receptor 1 (ESR1) mutation. The secondary objectives are to evaluate: 1. Clinical benefit rate (CBR) and Objective Response Rate (ORR) 2. Duration of response 3. Time to response 4. Overall Survival (OS) 5. Pharmacokinetics of lasofoxifene 6. Quality of life (QoL): Quality of Life (QoL): vaginal assessment scale (VAS) and vulvar assessment scale (VuAS) questionnaires 7. Safety of lasofoxifene 8. Response to various ESR1 mutation (Y537S, Y537C, D538G, E380Q, S463P, V534E, P535H, L536H, L536P, L536R, L536Q, or Y537N).
NCT03781063 Locally Advanced or Metastatic Breast Cancer Drug: Lasofoxifene Drug: Fulvestrant MeSH:Breast Neoplasms
HPO:Breast carcinoma Neoplasm of the breast
The secondary objectives are to evaluate: 1. Clinical benefit rate (CBR) and Objective Response Rate (ORR) 2. Duration of response 3. Time to response 4. Overall Survival (OS) 5. Pharmacokinetics of lasofoxifene 6. Quality of life (QoL): Quality of Life (QoL): vaginal assessment scale (VAS) and vulvar assessment scale (VuAS) questionnaires 7. Safety of lasofoxifene 8. Response to various ESR1 mutation (Y537S, Y537C, D538G, E380Q, S463P, V534E, P535H, L536H, L536P, L536R, L536Q, or Y537N). --- Y537S ---
At least one or more of the following point ESR1 mutations as assessed in cell-free circulating tumor DNA (ctDNA) obtained from a blood (plasma) or tissue sample: Y537S, Y537C, D538G, E380Q, S463P, V534E, P535H, L536H, L536P, L536R, L536Q, or Y537N. --- Y537S ---
Each of these stratified groups will then be further stratified into those with the Y537S ESR1 mutation and those without this particular mutation. --- Y537S ---
Primary Outcomes
Description: PFS is defined as the interval from the date of randomization to the earlier date of first documented radiographic progression or death due to any cause
Measure: Progression-Free Survival (PFS) Time: through study completion, an average of 1 yearSecondary Outcomes
Description: CBR is defined as the percentage of all subjects with a complete or partial response; or stable disease for >/=24 weeks.
Measure: Clinical Benefit Rate (CBR) Time: through study completion, an average of 1 yearDescription: ORR is defined as the percentage of subjects with either a complete response (CR) or a partial response (PR) as assessed by the RECIST 1.1 criteria.
Measure: Objective Response Rate (ORR) Time: through study completion, an average of 1 yearDescription: OS is defined as time from randomization to death due to any cause.
Measure: Overall Survival (OS) Time: through study completion, an average of 1 yearDescription: The type, severity (graded by Common Terminology Criteria for Adverse Events [CTCAE version 5.0]), course, duration, seriousness, and relationship to study treatment will be assess at each visit
Measure: Incidence of Adverse Events (AEs) and Serious AEs Time: through study completion, an average of 1 year3 The Landscape of ESR1 Mutations in Asian Estrogen Receptor-positive Metastatic Breast Cancer Patients Detected by Liquid Biopsy and Impact on Hormonal Therapy-based Treatments
The investigator propose a prospective study using blood samples (liquid biopsy) of estrogen receptor (ER)-positive metastatic breast cancer (MBC) patients to understand the prevalence of estrogen receptor 1 (ESR1) mutation variants and the correlation with hormonal therapy (HT)-based treatment resistance in Asian ER-positive/human epidermal growth receptor-2 (HER2)-negative MBC population.
NCT04212702 Metastatic Breast Cancer Drug: Hormonal therapy-based treatments MeSH:Breast Neoplasms
HPO:Breast carcinoma Neoplasm of the breast
For the second purpose, the investigator will specifically focus on patients with ESR1 Y537C mutation, while the results from patients with wild type ESR1 and patients with D538G or Y537S mutant will be severed as control for preliminary comparison. --- Y537C --- --- D538G --- --- Y537S ---
Primary Outcomes
Description: The percentage of each ESR1 LBD mutation variant in Asian ER-positive/HER2-negative MBC who had received at least one line of HT
Measure: The percentage of ESR1 LBD mutation variant Time: 12 monthsSecondary Outcomes
Description: PFS of patients who are treated with everolimus plus HT with either ESR1 wild type or different Asian-specific prevalent ESR1 LBD mutation variants such as Y537C
Measure: Progression-free Survival (PFS) Time: 12 months4 INTERACT- Integrated Evaluation of Resistance and Actionability Using Circulating Tumor DNA in HR Positive Metastatic Breast Cancers
This phase II trial studies how well letrozole, anastrozole, or fulvestrant work when given together with ribociclib, palbociclib, and/or abemaciclib in treating patients with hormone receptor (HR) positive breast cancer that has spread to other places in the body (metastatic) and has an ERS1 activating mutation. Letrozole, anastrozole, ribociclib, palbociclib, and abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Hormone therapy using fulvestrant may fight breast cancer by blocking the use of estrogen by the tumor cells. It is not yet known if giving letrozole, anastrozole, or fulvestrant with ribociclib, palbociclib, and/or abemaciclib will work better in treating patients with breast cancer.
NCT04256941 Anatomic Stage IV Breast Cancer AJCC v8 Metastatic Breast Carcinoma Prognostic Stage IV Breast Cancer AJCC v8 Drug: Abemaciclib Drug: Anastrozole Drug: Fulvestrant Drug: Letrozole Drug: Palbociclib Drug: Ribociclib MeSH:Breast Ne Breast Neoplasms
HPO:Breast carcinoma Neoplasm of the breast
D538G, Y537S/N, S463P) identified on ctDNA. --- D538G --- --- Y537S ---
Primary Outcomes
Description: Survival curves for PFS will be analyzed using the Kaplan-Meier method and survival difference across groups will be examined by log rank test. Will estimate the treatment comparison with 95% confidence intervals and p-value using Cox proportional hazards regression and we will assess the proportional hazard assumption using graphs of rescaled Schoenfeld residuals and related tests.
Measure: Progression-free survival (PFS) Time: Up to 30 daysSecondary Outcomes
Description: Graphical analysis, such as scatter plots with Lowess smoothers, will be used to assess the correlative structure of outcomes and compare MAF between fulvestrant and aromatase inhibitor-treated groups. The Pearson correlation, or its non-parametric analogue, the Spearman correlation, will be used to estimate the linear correlation among variables.
Measure: Circulating tumor deoxyribonucleic acid (ctDNA) ESR1 mutant allele fraction (MAF) and kinetics Time: Up to 30 daysDescription: Will be assessed by the secondary resistance of endocrine therapy.
Measure: Prevalence of Emergence of Estrogen Receptor 1 (ESR1) mutations Time: Up to 30 daysDescription: Will correlate ctDNA with CA 15-3 tumor marker changes.
Measure: Changes in cancer antigens (CA) 15-3 tumor marker Time: Up to 30 daysDescription: Survival curves for OS will be analyzed using the Kaplan-Meier method and survival difference across groups will be examined by log rank test. Will estimate the treatment comparison with 95% confidence intervals and p-value using Cox proportional hazards regression and we will assess the proportional hazard assumption using graphs of rescaled Schoenfeld residuals and related tests.
Measure: Overall survival (OS) Time: Up to 30 daysDescription: Will be assessed on next line of therapy after progression.
Measure: Time to next treatment Time: Up to 30 days5 An Open-label, Multicenter Study Evaluating the Safety of Lasofoxifene in Combination With Abemaciclib for the Treatment of Pre- and Postmenopausal Women With Locally Advanced or Metastatic ER+/HER2− Breast Cancer and Have an ESR1 Mutation ( ELAINEII )
This is an open-label, multicenter, single-arm safety study evaluating the safety and tolerability of the lasofoxifene and abemaciclib combination for the treatment of pre- and postmenopausal women with locally advanced or metastatic ER+/HER2− breast cancer who have disease progression on first and/or 2nd lines of hormonal treatment for metastatic disease and have an ESR1 mutation.
NCT04432454 Metastatic Breast Cancer Drug: Lasofoxifene and abemaciclib (VERZENIO (R). MeSH:Breast Neoplasms
HPO:Breast carcinoma Neoplasm of the breast
At least one or more of the following ESR1 point mutations as assessed in cell-free circulating tumor DNA (ctDNA) obtained from a blood or tissue sample: Y537S, Y537C, D538G, E380Q, S463P, V534E, P535H, L536H, L536P, L536R, L536Q, or Y537N. --- Y537S ---
Primary Outcomes
Description: AEs will be assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Measure: Safety and tolerability of the combination of lasofoxifene and abemaciclib as measured by number of adverse events (AEs), severity of AEs and mortality due to AEs at every scheduled visit. Time: All subjects enrolled in the study will be treated until documented disease progression or until withdrawal for any reason. Safety and tolerability will be assessed from enrollment up to 24 months.Secondary Outcomes
Description: PFS is defined as the time from the date of entry into the study to the earliest date of first documented progression or death due to any cause.
Measure: Progression free survival (PFS) Time: Up to 24 monthsMeasure: Clinical benefit rate (CBR) Time: 24 weeks or longer
Measure: Objective response rate (ORR) Time: All subjects enrolled in the study will be treated until documented disease progression or until withdrawal for any reason. ORR will be assessed up to 24 months.
Description: DoR is from the date of first documented response (CR or PR) to the date of first documented progression of disease or death due to any cause.
Measure: Duration of response (DoR) Time: DoR will be assessed up to 24 months.Description: From the date of entry into the study to the date of first documented response (CR or PR).
Measure: Time to response Time: Time to response will be assessed up to 24 months.Measure: Steady-state pharmacokinetics (PK) sampling for lasofoxifene and abemaciclib concentrations as well as abemaciclib's 3 major metabolites of lasofoxifene and abemaciclib Time: Baseline and pre-dose at every visit starting at Visit 0 (Day 1) through Visit 4 (Week 8) and at the Final/ET visit if this occurred prior to Week 8