SNPMiner Trials by Shray Alag


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Report for Mutation Y537C

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 3 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 If a patient progresses during the treatment period, the patient must be withdrawn from the treatment and further treatment will be at the investigator's discretion.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 ---

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 --- --- Y537C ---

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 --- --- Y537C ---

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 year

Secondary 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 year

Description: 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 year

Description: 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 year

Description: 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 year

3 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

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. --- Y537C ---

Metastatic Breast Cancer Breast Neoplasms The investigator will use next-generation targeted sequencing covering the entire ESR1 ligand-binding domain (LBD) region to understand 1. the spectrum and prevalence of specific ESR1 mutation variants in Asian women, and 2. the preliminary correlation of Asian-specific prevalent ESR1 LBD mutation variants such as Y537C with treatment efficacy. --- Y537C ---

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 ---

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 months

Secondary 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 months


HPO Nodes


Breast carcinoma
Genes 95
TP53 PPM1D CTNNB1 TP53 COL14A1 AKT1 AKT1 OPCML MDM2 BRCA1 SLC22A18 POLE BRCA2 BRCA1 SDHC NTHL1 PTEN XRCC3 MSH6 IDH1 RAD51C RAD51C CASP8 RB1CC1 PIK3CA PALLD KRAS PIK3CA CHEK2 BRIP1 MRE11 NTHL1 ATM TP53 RAD51D STK11 PRKN ESR1 PIK3CA KLLN MSH2 SDHD KRAS SEC23B HMMR PTEN POLD1 PIK3CA IDH2 BRCA1 PALB2 BRIP1 TP53 RAD51 RNF43 BARD1 BARD1 AAGAB AKT1 SMAD4 RAD50 STK11 CHEK2 RAD54L NBN CDKN2A SEC23B CDH1 WRN NQO2 PALB2 ATR PALB2 TWIST1 SDHB MSH2 BRCA2 BRCA1 RAD51 CHEK2 MLH1 BRCA1 FGFR2 TP53 PHB BRCA2 CDH1 PTEN BRCA2 CHEK2 CDKN2A APC MLH1 AKT1 APC