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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.
Sponsor: Institut Claudius Regaud
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.
Official title: 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.
Key Details
Gender
All
Age Range
18 Years - Any
Study Type
INTERVENTIONAL
Enrollment
120
Start Date
2022-06-23
Completion Date
2027-06
Last Updated
2026-02-20
Healthy Volunteers
No
Conditions
Interventions
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.
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 (25)
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
INSTITUT DE CANCEROLOGIE DE L'OUEST St-Herblain
Saint-Herblain, France
IUCT-O
Toulouse, France
Chru de Tours
Tours, France
Institut de Cancerologie de Lorraine
Vandœuvre-lès-Nancy, France
Institut Gustave Roussy
Villejuif, France