NCT05378204招募中不适用
Prospective and Multicentric Study Evaluating DNA Double-strand Breaks (DSBs) REpair Factors (POLQ, Shieldin Complex and 53BP1) Expression as Biomarker of PARP Inhibitor Resistance in Patients With Deleterious Germline Mutation in BRCA 1/2 and HER2-negative, Metastatic or Locally Advanced Breast Cancer.
适应症
干预措施
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 27
- 主要终点
- Main study: the primary endpoint is the Area under the Receiver Operating Characteristic Curve (ROC Curve) of POLQ expression to identify patients presenting progressive disease or death at 6 months under PARPi alone (primary resistance).
研究概览
简要总结
The purpose of this study is to assess whether expression of not only POLQ/Polθ, but also Shieldin complex and/or 53BP1 are correlated with primary and/or acquired resistance to PARPi (Poly(ADP-Ribose) Polymerases inhibitors) in a sub-population of locally advanced or metastatic breast cancer patients and vary regarding type and location of gBRCA1/2 mutations.
This translational research program is composed of two multicentric, non-randomized prospective studies in patients with HER2-negative locally advanced or metastatic breast cancer:
- The main study concerns 80 patients eligible for PARPi (according to the investigators).PARPi treatments (talazoparib or olaparib) will be administered and dosed according to the standard of care administration.
- The sub-study concerns 40 patients in progression disease under PARPi alone.
For each included patient in the main study or sub-study, tumor biopsy specimen and blood samples will be collected at different times during the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Women (or men) aged ≥ 18 years with histologically proven breast cancer
- •Metastatic relapse or locally advanced breast cancer
- •No-HER2 overexpression or amplification
- •Triple-negative (defines as ER<1%, PR<1% and HER2-negative as per ASCO CAP guidelines) or hormone receptor positive (defines as ER and/or PR ≥ 1%) breast cancer
- •Patients with metastases that can be biopsied except bone metastases. At baseline, if patients already have an archived biopsy from a secondary or a primary site (if stage IV) of their current disease, this material can be used for the study, provided that, it was collected within 3 months prior enrollment and a frozen and a FFPE sample are both available for research
- •ECOG Performance Status ≤ 2
- •Patients must have measurable or evaluable disease according to RECIST v1.1
- •Patient with deleterious germline BRCA 1 and/or 2 mutation, eligible for PARP inhibitor therapy (olaparib or talazoparib), according each investigator
- •Any number of prior lines therapy are allowed
- •Current treatment with PARP inhibitor not yet started
- •Women should be post-menopaused or willing to accept the use of an effective contraceptive regimen during the treatment period by PARP inhibitor
- •Patient able to participate and willing to give informed consent prior performance of any study-related procedures and to comply with the study protocol
- •Patient affiliated to a Social Health Insurance in France
- •NON-INCLUSION CRITERIA:
- •Abnormal coagulation contraindicating biopsy
- •Bone metastases when this is the only site of biopsiable disease
- •Patients with all target in a previously irradiated region, except if clear progression has been observed prior to study in at least one of them
- •Patients with known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
- •Patients with known untreated CNS metastases and/or carcinomatous meningitis
- •Patients with a known history of Human Immunodeficiency Virus (HIV)
- •Patients with known active Hepatitis B or C
- •Patients should not be on any other anti-cancer therapy (chemotherapy, endocrine therapy, immunotherapy, tailored therapy or alternative investigational therapy)
- •Patient pregnant, or breast-feeding
- •Any psychological, familial, geographic or social situation, according to the judgment of investigator, potentially preventing the provision of informed consent or compliance to study procedure
- •Patient who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice)
- •INCLUSION CRITERIA:
- •Women (or men) aged ≥ 18 years with histologically proven breast cancer
- •Metastatic relapse or locally advanced breast cancer
- •No-HER2 overexpression or amplification
- •Triple-negative (defines as ER<1%, PR<1% and HER2-negative as per ASCO CAP guidelines) or hormone receptor positive (defines as ER and or PR ≥ 1%) breast cancer
- •Patients with metastases that can be biopsied except bone metastases
- •ECOG Performance Status ≤ 2
- •Patients, with deleterious germline BRCA 1 and/or 2, in progression under PARPi alone (talazoparib or olaparib)
- •Patient able to participate and willing to give informed consent prior performance of any study-related procedures and to comply with the study protocol
- •Patient affiliated to a Social Health Insurance in France
- •NON-INCLUSION CRITERIA:
- •Abnormal coagulation contraindicating biopsy
- •Bone metastases when this is the only site of biopsiable disease
- •Patient pregnant, or breast-feeding
- •Patients with a known history of Human Immunodeficiency Virus (HIV)
- •Patients with known active Hepatitis B or C
- •Any psychological, familial, geographic or social situation, according to the judgment of investigator, potentially preventing the provision of informed consent or compliance to study procedure
- •Patients already participating in the main REPARP study
- •Patient who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice)
排除标准
- 未提供
研究组 & 干预措施
Patients with breast cancer
Other
Patients With Deleterious Germline Mutation in BRCA 1/2 and HER2-negative, Metastatic or Locally Advanced Breast Cancer.
干预措施: Main study: (Other)
Patients with breast cancer
Other
Patients With Deleterious Germline Mutation in BRCA 1/2 and HER2-negative, Metastatic or Locally Advanced Breast Cancer.
干预措施: Sub-study: (Other)
结局指标
主要结局
Main study: the primary endpoint is the Area under the Receiver Operating Characteristic Curve (ROC Curve) of POLQ expression to identify patients presenting progressive disease or death at 6 months under PARPi alone (primary resistance).
时间窗: 6 months for each patient
Progression will be determined using RECIST v1.1 criteria.
Sub-study: the primary end point is the rate of patients presenting loss of Shieldin complex and/or 53BP1.
时间窗: 1 month for each patient
次要结局
- Main study: Objective Response (i.e. complete or partial response) defined using RECIST v1.1 criteria.(12 months for each patient)
- Main study: Progression-Free Survival defined as the time from inclusion until progression according to RECIST v1.1 criteria or death from any cause, whichever occurs first.(12 months for each patient)
- Main study: Duration Of Response defined as the time from initial objective response until progression according to RECIST v1.1 criteria or death from any cause.(12 months for each patient)
- Sub-study: expression of the Shieldin complex and 53BP1.(1 month for each patient)
研究者
研究点 (27)
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