Breast CancerREPARPNCT05378204
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.
A study testing Main study: and Sub-study: in people with Breast Cancer, run by Institut Claudius Regaud at 25 sites in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Main study: and Sub-study:
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 25 sitesFrance
- Study dates
- 23 Jun 2022to Jun 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 44Show fewer
- 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
- NON-INCLUSION CRITERIA:
- Abnormal coagulation contraindicating biopsy
- Bone metastases when this is the only site of biopsiable disease
- 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
- 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
- Patients with known untreated CNS metastases and/or carcinomatous meningitis
- Patients with a known history of Human Immunodeficiency Virus (HIV)
- Patients with known active Hepatitis B or C
- Patients should not be on any other anti-cancer therapy (chemotherapy, endocrine therapy, immunotherapy, tailored therapy or alternative investigational therapy)
- Patient pregnant, or breast-feeding
- 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
- 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
- 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
- ECOG Performance Status ≤ 2
- Patients, with deleterious germline BRCA 1 and/or 2, in progression under PARPi alone (talazoparib or olaparib)
- 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
- NON-INCLUSION CRITERIA:
- Abnormal coagulation contraindicating biopsy
- Bone metastases when this is the only site of biopsiable disease
- Patient pregnant, or breast-feeding
- Patients with a known history of Human Immunodeficiency Virus (HIV)
- Patients with known active Hepatitis B or C
- 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
- Patients already participating in the main REPARP study
- Patient who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice)
Who cannot join
None listed.
Trial locations and contacts
25 sites in 1 country. Contact the study team or a site near you to ask about taking part.
25 sites in 1 country
France25 sites, 22 recruiting
- Recruiting
Institut Bergonie
Bordeaux
Monica ARNEDOS, 05 56 33 32 38, m.arnedos@bordeaux.unicancer.fr
- Recruiting
Centre Francois Baclesse
Caen
Georges EMILE, 02 31 45 50 50, g.emile@baclesse.unicancer.fr
- Recruiting
Centre Jean Perrin
Clermont-Ferrand
Xavier DURANDO, 04 73 27 80 00, xavier.durando@clermont.unicancer.fr
- Withdrawn
Centre Georges Francois Leclerc
Dijon
- Recruiting
Centre Hospitalier Départemental Vendée
La Roche-sur-Yon
Frank PRIOU, 02 51 44 61 73, frank.priou@ght85.fr
- Recruiting
Centre Oscar Lambret
Lille
Nawale HAJJAJI, 03 20 29 59 59, n-hajjaji@o-lambret.fr
- Recruiting
CHU de LIMOGES
Limoges
Elise DELUCHE, 05 55 05 61 00, elise.deluche@chu-limoges.fr
- Recruiting
Centre Leon Berard
Lyon
Olivier TREDAN, 04 78 78 26 44, olivier.tredan@lyon.unicancer.fr
- Recruiting
Institut Paoli Calmettes
Marseille
Anthony GONCALVES, 04 91 22 37 89, GONCALVESA@ipc.unicancer.fr
- Recruiting
Centre de Cancerologie Du Grand Montpellier
Montpellier
Cristian VILLANUEVA, 04 67 92 61 55, cvillanueva@oncoclem.org
- Recruiting
Institut Regional Du Cancer de Montpellier
Montpellier
William JACOT, 04 67 61 23 39, william.jacot@icm.unicancer.fr
- Recruiting
CHU de Nimes
Nîmes
Frédéric FITENI, 04 66 68 33 01, Frederic.fiteni@chu-nimes.fr
- Recruiting
Hopital Pitie Salpetriere
Paris
Jean-Philippe SPANO, 01 42 16 04 72, jean-philippe.spano@aphp.fr
- Recruiting
Hopital Saint Louis
Paris
Luis TEIXEIRA, 01 42 49 42 62, luis.teixeira@aphp.fr
- Recruiting
Hopital Tenon
Paris
Joseph GLIGOROV, 01 56 01 63 73, joseph.gligorov@aphp.fr
- Withdrawn
INSTITUT CURIE - Site de Paris
Paris
- Not yet recruiting
CENTRE ARMORICAIN DE RADIOTHERAPIE, IMAGERIE MEDICALE ET ONCOLOGIE - Hôpital privé des Côtes d'Armor
Plérin
Anne-Claire HARDY-BESSARD, 02 96 75 22 16, ac.hardy@cario-sante.fr
- Recruiting
Chu de Poitiers
Poitiers
Nicolas ISAMBERT, 05 49 44 45 48, nicolas.isambert@chu-poitiers.fr
- Withdrawn
Centre Eugene Marquis
Rennes
- Recruiting
Chu Saint Etienne
Saint-Etienne
Gilles FREYER, 04 77 91 70 00, gilles.freyer@chu-st-etienne.fr
- Recruiting
INSTITUT DE CANCEROLOGIE DE L'OUEST St-Herblain
Saint-Herblain
Jean-Sébastien FRENEL, 02 40 67 99 00, jean-sebastien.frenel@ico.unicancer.fr
- Recruiting
IUCT-O
Toulouse
Florence DALENC, Dalenc.Florence@iuct-oncopole.fr
- Recruiting
Chru de Tours
Tours
Hélène VEGAS, 02 47 47 99 19, h.vegas@chu-tours.fr
- Recruiting
Institut de Cancerologie de Lorraine
Vandœuvre-lès-Nancy
Anne KIEFFER, 03 83 59 85 64, a.kieffer@nancy.unicancer.fr
- Recruiting
Institut Gustave Roussy
Villejuif
Suzette DELALOGE, 01 42 11 51 27, suzette.delaloge@gustaveroussy.fr
About this 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.
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:
Read more
- 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
- Being tested
- Main study:, Sub-study:
- Keywords
- Breast cancer, Germline BRCA mutation, PARP inhibitor, Biomarkers, POLQ, Polθ, Shieldin complex, 53BP1
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
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).
| Study group | Role | What they receive |
|---|---|---|
| Patients with breast cancer | Other | Patients With Deleterious Germline Mutation in BRCA 1/2 and HER2-negative, Metastatic or Locally Advanced Breast Cancer. Receives: Other: Main study:; Other: Sub-study: |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months for each patient
Sub-study: the primary end point is the rate of patients presenting loss of Shieldin complex and/or 53BP1.
Measured: 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.
Measured: 12 months for each patient
Main study: Objective Response (i.e. complete or partial response) defined using RECIST v1.1 criteria.
Measured: 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.
Measured: 12 months for each patient
Sub-study: expression of the Shieldin complex and 53BP1.
Measured: 1 month for each patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2022
- Study start23 Jun 2022
- Primary completionJan 2027 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institut Claudius Regaud
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05378204
- Sponsor's protocol ID
- 21 SEIN 09
- Acronym
- REPARP
- Status last verified
- Feb 2026
- First submitted
- 11 May 2022
- Last updated
- 20 Feb 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT05378204
- Acronym / sponsor ID
- REPARP / 21 SEIN 09
- Conditions
- Breast Cancer
- Keywords
- Breast cancer, Germline BRCA mutation, PARP inhibitor, Biomarkers, POLQ, Polθ, Shieldin complex, 53BP1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Institut Claudius RegaudUniversity, hospital or other
- Study start
- 23 Jun 2022 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Jun 2027 (estimated)
- First posted
- 18 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with breast cancer | Other | Other: Main study:, Other: Sub-study:Patients With Deleterious Germline Mutation in BRCA 1/2 and HER2-negative, Metastatic or Locally Advanced Breast Cancer. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (44 listed)
- 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
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Patients with breast cancer |
| 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). | Other | Patients with breast cancer |
Primary outcome
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).
Time frame: 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.
Time frame: 1 month for each patient
4 secondary outcomes
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.
Time frame: 12 months for each patient
Main study: Objective Response (i.e. complete or partial response) defined using RECIST v1.1 criteria.
Time frame: 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.
Time frame: 12 months for each patient
Sub-study: expression of the Shieldin complex and 53BP1.
Time frame: 1 month for each patient
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
25 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Main study: and Sub-study: in people with Breast Cancer, run by Institut Claudius Regaud at 25 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 44 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Florence DALENC (05 31 15 51 04, Dalenc.Florence@iuct-oncopole.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). (time frame: 6 months for each patient). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2026.