RecruitingNot ApplicableNCT05378204

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.


Sponsor

Institut Claudius Regaud

Enrollment

120 participants

Start Date

Jun 23, 2022

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This study is looking at whether certain proteins involved in DNA repair (POLQ, Shieldin, and 53BP1) can predict whether a patient's breast cancer will stop responding to a class of drugs called PARP inhibitors, which are commonly used in BRCA-mutated breast cancer. **You may be eligible if...** - You are 18 or older with confirmed breast cancer that has spread or is locally advanced - Your tumor does not overexpress HER2 - You carry a harmful mutation in the BRCA1 or BRCA2 gene - You are about to start (but have not yet started) PARP inhibitor treatment (olaparib or talazoparib) - A tumor biopsy is possible and tumor tissue samples are available - You are enrolled in the French health insurance system **You may NOT be eligible if...** - You have abnormal blood clotting that makes a biopsy unsafe - Your only cancer site is in the bone, which cannot be biopsied - You are already on PARP inhibitor therapy Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

OTHERMain 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.

OTHERSub-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

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NCT05378204


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