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RECRUITINGINTERVENTIONAL

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.

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.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

Who May Be Eligible (Plain English)

MAIN STUDY Who May Qualify: 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 willing to sign a consent form 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-Who May Qualify: 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 ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
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)

Treatments Being Tested

OTHER

Main study:

For each included patient, tumor biopsy specimen and blood samples will be collected at baseline visit (before the first dose of PARPi treatment). During the treatment period: blood samples will be scheduled every 8 weeks (i.e. 2 cycles). At the time of progression: tumor biopsy and blood samples will be collected.

OTHER

Sub-study:

For each included patient, tumor biopsy specimen and blood samples will be collected as soon as possible after progression (before initiation of the post PARPi anti-tumoral treatment).

Locations (20)

Institut Bergonie
Bordeaux, France
Centre Francois Baclesse
Caen, France
Centre Jean Perrin
Clermont-Ferrand, France
Centre Georges Francois Leclerc
Dijon, France
Centre Hospitalier Départemental Vendée
La Roche-sur-Yon, France
Centre Oscar Lambret
Lille, France
CHU de LIMOGES
Limoges, France
Centre Leon Berard
Lyon, France
Institut Paoli Calmettes
Marseille, France
Centre de Cancerologie Du Grand Montpellier
Montpellier, France
Institut Regional Du Cancer de Montpellier
Montpellier, France
CHU de Nimes
Nîmes, France
Hopital Pitie Salpetriere
Paris, France
Hopital Saint Louis
Paris, France
Hopital Tenon
Paris, France
INSTITUT CURIE - Site de Paris
Paris, France
CENTRE ARMORICAIN DE RADIOTHERAPIE, IMAGERIE MEDICALE ET ONCOLOGIE - Hôpital privé des Côtes d'Armor
Plérin, France
Chu de Poitiers
Poitiers, France
Centre Eugene Marquis
Rennes, France
Chu Saint Etienne
Saint-Etienne, France