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Evaluating biomarkers for PARP inhibitor resistance in breast cancer patients with BRCA mutations

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.

Not applicable Interventional Institut Claudius Regaud · NCT05378204

This study is testing if certain DNA repair factors can help explain why some breast cancer patients with BRCA mutations don't respond to PARP inhibitors.

Quick facts

PhaseNot applicable
Study typeInterventional
Enrollment120 (estimated)
Ages18 Years and up
SexAll
SponsorInstitut Claudius Regaud Academic / other
Drugs / interventionschemotherapy, immunotherapy
Locations25 sites (Bordeaux and 24 other locations)
Trial IDNCT05378204 on ClinicalTrials.gov

What this trial studies

This study aims to investigate the correlation between the expression of specific DNA repair factors (POLQ, Shieldin complex, and 53BP1) and resistance to PARP inhibitors in patients with HER2-negative, locally advanced or metastatic breast cancer who have deleterious germline BRCA1/2 mutations. It consists of two multicentric, non-randomized prospective studies: the main study involving 80 patients eligible for PARP inhibitor treatment and a sub-study involving 40 patients experiencing disease progression while on PARP inhibitors. Tumor biopsies and blood samples will be collected at various points to assess the relationship between biomarker expression and treatment outcomes.

Who should consider this trial

Good fit: Ideal candidates include adults with HER2-negative, locally advanced or metastatic breast cancer and deleterious germline BRCA1/2 mutations who are eligible for PARP inhibitor therapy.

Not a fit: Patients with breast cancer who do not have BRCA mutations or those with HER2-positive tumors may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could help identify biomarkers that predict resistance to PARP inhibitors, potentially leading to more personalized and effective treatment strategies for breast cancer patients.

How similar studies have performed: Other studies have shown promise in identifying biomarkers related to PARP inhibitor resistance, making this approach both relevant and potentially impactful.

Eligibility criteria

Show full inclusion / exclusion 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)

Where this trial is running

Bordeaux and 24 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Breast CancerBreast cancerGermline BRCA mutationPARP inhibitorBiomarkersPOLQPolθShieldin complex
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.