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. (REPARP)

Institut Claudius Regaud

Status

Enrolling

Conditions

Breast Cancer

Treatments

Other: Sub-study:

Other: Main study:

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT05378204

21 SEIN 09

Details and patient eligibility

About

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.

Enrollment

120 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

MAIN STUDY

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. 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)

SUB-STUDY

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)