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.

NCT05378204 | Recruiting

• 1 other identifier: 21 SEIN 09
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 25

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.

Conditions

Breast Cancer

Keywords

Breast cancer; Germline BRCA mutation; PARP inhibitor; Biomarkers; POLQ; Polθ; Shieldin complex; 53BP1

Outcome Measures

Primary Outcomes (2)

• 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).

  Progression will be determined using RECIST v1.1 criteria.

  6 months for each patient

• 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 Outcomes (4)

• 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: Objective Response (i.e. complete or partial response) defined using RECIST v1.1 criteria.

  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

Study Arms (1)

Patients with breast cancer

OTHER

Patients With Deleterious Germline Mutation in BRCA 1/2 and HER2-negative, Metastatic or Locally Advanced Breast Cancer.

Other: Main study:; Other: Sub-study:

Interventions

Main study: OTHER

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.

Patients with breast cancer

Sub-study: OTHER

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).

Patients with breast cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women (or men) aged ≥ 18 years with histologically proven breast cancer
• Metastatic relapse or locally advanced breast cancer
• No-HER2 overexpression or amplification
• 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
• 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
• ECOG Performance Status ≤ 2
• Patients must have measurable or evaluable disease according to RECIST v1.1
• Patient with deleterious germline BRCA 1 and/or 2 mutation, eligible for PARP inhibitor therapy (olaparib or talazoparib), according each investigator
• Any number of prior lines therapy are allowed
• Current treatment with PARP inhibitor not yet started
• Women should be post-menopaused or willing to accept the use of an effective contraceptive regimen during the treatment period by PARP inhibitor
• Patient able to participate and willing to give informed consent prior performance of any study-related procedures and to comply with the study protocol
• Patient affiliated to a Social Health Insurance in France
• Abnormal coagulation contraindicating biopsy
• Bone metastases when this is the only site of biopsiable disease

Sponsors & Collaborators

• Institut Claudius Regaud: lead

Study Sites (25)

Institut Bergonie

Bordeaux, France

RECRUITING

Centre Francois Baclesse

Caen, France

RECRUITING

Centre Jean Perrin

Clermont-Ferrand, France

RECRUITING

Centre Georges Francois Leclerc

Dijon, France

WITHDRAWN

Centre Hospitalier Départemental Vendée

La Roche-sur-Yon, France

RECRUITING

Centre Oscar Lambret

Lille, France

RECRUITING

CHU de LIMOGES

Limoges, France

RECRUITING

Centre Leon Berard

Lyon, France

RECRUITING

Institut Paoli Calmettes

Marseille, France

RECRUITING

Centre de Cancerologie Du Grand Montpellier

Montpellier, France

RECRUITING

Institut Regional Du Cancer de Montpellier

Montpellier, France

RECRUITING

CHU de Nimes

Nîmes, France

RECRUITING

Hopital Pitie Salpetriere

Paris, France

RECRUITING

Hopital Saint Louis

Paris, France

RECRUITING

Hopital Tenon

Paris, France

RECRUITING

INSTITUT CURIE - Site de Paris

Paris, France

WITHDRAWN

CENTRE ARMORICAIN DE RADIOTHERAPIE, IMAGERIE MEDICALE ET ONCOLOGIE - Hôpital privé des Côtes d'Armor

Plérin, France

NOT YET RECRUITING

Chu de Poitiers

Poitiers, France

RECRUITING

Centre Eugene Marquis

Rennes, France

WITHDRAWN

Chu Saint Etienne

Saint-Etienne, France

RECRUITING

INSTITUT DE CANCEROLOGIE DE L'OUEST St-Herblain

Saint-Herblain, France

RECRUITING

IUCT-O

Toulouse, France

RECRUITING

Chru de Tours

Tours, France

RECRUITING

Institut de Cancerologie de Lorraine

Vandœuvre-lès-Nancy, France

RECRUITING

Institut Gustave Roussy

Villejuif, France

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Florence DALENC

CONTACT

05 31 15 51 04; Dalenc.Florence@iuct-oncopole.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2022
• First Posted: May 18, 2022
• Study Start: June 23, 2022
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: February 20, 2026

Record last verified: 2026-02

Locations

FR (25)