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.

Launched by INSTITUT CLAUDIUS REGAUD · May 17, 2022

Keywords

ClinConnect Summary

This clinical trial is investigating how certain factors in breast cancer cells relate to the effectiveness of a type of treatment called PARP inhibitors. These treatments are commonly used for patients with specific genetic mutations in their BRCA1 or BRCA2 genes. The study aims to find out if the levels of certain proteins (POLQ, Shieldin complex, and 53BP1) can help predict whether patients will respond to PARP inhibitors or if they might become resistant to the treatment over time. The trial includes two parts: one with patients who haven't started PARP inhibitor therapy yet, and another with patients whose cancer has continued to progress while on this treatment.

To be eligible for the study, participants must be at least 18 years old, have a confirmed diagnosis of locally advanced or metastatic breast cancer, and possess certain genetic markers. They should also be in a condition that allows them to undergo a biopsy, except for those with bone-only metastases. During the trial, participants will provide blood and tissue samples to help researchers better understand their tumors. Those who join can expect to receive standard PARP inhibitor treatments while also contributing to important research that could improve future breast cancer therapies.

Gender

ALL

Eligibility criteria

• • MAIN STUDY
• INCLUSION CRITERIA:
• • 1. Women (or men) aged ≥ 18 years with histologically proven breast cancer
• • 2. Metastatic relapse or locally advanced breast cancer
• • 3. No-HER2 overexpression or amplification
• • 4. 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
• • 5. 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
• • 6. ECOG Performance Status ≤ 2
• • 7. Patients must have measurable or evaluable disease according to RECIST v1.1
• • 8. Patient with deleterious germline BRCA 1 and/or 2 mutation, eligible for PARP inhibitor therapy (olaparib or talazoparib), according each investigator
• • 9. Any number of prior lines therapy are allowed
• • 10. Current treatment with PARP inhibitor not yet started
• • 11. Women should be post-menopaused or willing to accept the use of an effective contraceptive regimen during the treatment period by PARP inhibitor
• • 12. Patient able to participate and willing to give informed consent prior performance of any study-related procedures and to comply with the study protocol
• • 13. Patient affiliated to a Social Health Insurance in France
• NON-INCLUSION CRITERIA:
• • 1. Abnormal coagulation contraindicating biopsy
• • 2. Bone metastases when this is the only site of biopsiable disease
• • 3. 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
• • 4. 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
• • 5. Patients with known untreated CNS metastases and/or carcinomatous meningitis
• • 6. Patients with a known history of Human Immunodeficiency Virus (HIV)
• • 7. Patients with known active Hepatitis B or C
• • 8. Patients should not be on any other anti-cancer therapy (chemotherapy, endocrine therapy, immunotherapy, tailored therapy or alternative investigational therapy)
• • 9. Patient pregnant, or breast-feeding
• • 10. 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
• • 11. 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:
• • 1. Women (or men) aged ≥ 18 years with histologically proven breast cancer
• • 2. Metastatic relapse or locally advanced breast cancer
• • 3. No-HER2 overexpression or amplification
• • 4. 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
• • 5. Patients with metastases that can be biopsied except bone metastases
• • 6. ECOG Performance Status ≤ 2
• • 7. Patients, with deleterious germline BRCA 1 and/or 2, in progression under PARPi alone (talazoparib or olaparib)
• • 8. Patient able to participate and willing to give informed consent prior performance of any study-related procedures and to comply with the study protocol
• • 9. Patient affiliated to a Social Health Insurance in France
• NON-INCLUSION CRITERIA:
• • 1. Abnormal coagulation contraindicating biopsy
• • 2. Bone metastases when this is the only site of biopsiable disease
• • 3. Patient pregnant, or breast-feeding
• • 4. Patients with a known history of Human Immunodeficiency Virus (HIV)
• • 5. Patients with known active Hepatitis B or C
• • 6. 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
• • 7. Patients already participating in the main REPARP study
• • 8. Patient who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice)