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.
- Conditions
- Breast Cancer
- Registration Number
- NCT05378204
- Lead Sponsor
- Institut Claudius Regaud
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method 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). 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. 1 month for each patient
- Secondary Outcome Measures
Name Time Method 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
Trial Locations
- Locations (25)
Chru de Tours
🇫🇷Tours, France
Centre Hospitalier Départemental Vendée
🇫🇷La Roche-sur-Yon, France
Centre Leon Berard
🇫🇷Lyon, France
Chu de Poitiers
🇫🇷Poitiers, France
Hopital Tenon
🇫🇷Paris, France
Institut Regional Du Cancer de Montpellier
🇫🇷Montpellier, France
CHU de Nimes
🇫🇷Nîmes, France
Institut Paoli Calmettes
🇫🇷Marseille, France
Centre de Cancerologie Du Grand Montpellier
🇫🇷Montpellier, France
Centre Oscar Lambret
🇫🇷Lille, France
Centre Eugene Marquis
🇫🇷Rennes, France
CENTRE ARMORICAIN DE RADIOTHERAPIE, IMAGERIE MEDICALE ET ONCOLOGIE - Hôpital privé des Côtes d'Armor
🇫🇷Plérin, France
Institut Gustave Roussy
🇫🇷Villejuif, France
INSTITUT DE CANCEROLOGIE DE L'OUEST St-Herblain
🇫🇷Saint-Herblain, France
Hopital Saint Louis
🇫🇷Paris, France
Hopital Pitie Salpetriere
🇫🇷Paris, France
IUCT-O
🇫🇷Toulouse, France
Institut Bergonie
🇫🇷Bordeaux, France
Centre Francois Baclesse
🇫🇷Caen, France
CHU de LIMOGES
🇫🇷Limoges, France
Centre Jean Perrin
🇫🇷Clermont-Ferrand, France
Centre Georges Francois Leclerc
🇫🇷Dijon, France
Chu Saint Etienne
🇫🇷Saint-Étienne, France
Institut de Cancerologie de Lorraine
🇫🇷Vandoeuvre-les-nancy, France
INSTITUT CURIE - Site de Paris
🇫🇷Paris, France