Capecitabine Plus Pembrolizumab in Patients With Triple Negative Breast Cancer After Chemo-immunotherapy and Surgery

NCT ID: NCT05973864

Last Updated: 2025-11-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 220 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-11
• Study Completion Date: 2028-08-31

Brief Summary

The goal of this clinical trial is to evaluate the efficacity and safety of pembrolizumab and capecitabine on the invasive disease-free survival, in participants who have triple negative breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy associated with pembrolizumab.

Detailed Description

We propose to evaluate the benefit in 2-year iDFS and safety of adding capecitabine to pembrolizumab in post-operative phase of pembrolizumab-containing treatment, in the subgroup of localized TNBC patients with residual disease.

An external cohort with patients treated with pembrolizumab as part of standard care after surgery, for localized TNBC without pCR after NAC, and with similar eligibility criteria, will be registered in an ambispective way, allowing comparisons between the experimental arm and this external cohort. All the centers involved in the study will participate in the registration of the needed information concerning this cohort.

Conditions

Triple Negative Breast Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental arm : Pembrolizumab and capecitabine

• Pembrolizumab will be administered at a fixed dose of 200 mg every 3 weeks (Q3W), with a total of 9 cycles at adjuvant phase of the treatment;
• Capecitabine will be administrated at a dose of 1250 mg/m² twice a day (BID) (14 days on / 7 days off) for a total of 8 cycles, with a dose reduction at 825 mg/m² BID during radiotherapy if indicated
• Local radiotherapy will be performed as per standard practice if indicated.

Group Type: EXPERIMENTAL

Pembrolizumab injection

Intervention Type: DRUG

On Day 1 of each cycle for a total of 9 cycles; intravenous (IV) infusion

Capecitabine tablets

Intervention Type: DRUG

1250 mg/m² BID, on days 1-14 of each 21-day cycle; 8 cycles Dose reduction at 825 mg/m² BID during radiotherapy if indicated

Local radiotherapy

Intervention Type: RADIATION

Local radiotherapy will be performed as per standard practice if indicated.

Standard of care (SOC) treated external cohort

A standard of care treated external cohort with patients treated with pembrolizumab as postoperative treatment for localized TNBC without pCR after NAC, and with similar eligibility criteria will be registered in an ambispective way, allowing comparisons between the experimental arm and this external cohort. All the centres involved in the study will participate the registration of the needed information concerning this cohort.

Group Type: OTHER

Pembrolizumab injection

Intervention Type: DRUG

On Day 1 of each cycle for a total of 9 cycles; intravenous (IV) infusion

Local radiotherapy

Intervention Type: RADIATION

Local radiotherapy will be performed as per standard practice if indicated.

Interventions

Pembrolizumab injection

On Day 1 of each cycle for a total of 9 cycles; intravenous (IV) infusion

Intervention Type: DRUG

Capecitabine tablets

1250 mg/m² BID, on days 1-14 of each 21-day cycle; 8 cycles Dose reduction at 825 mg/m² BID during radiotherapy if indicated

Intervention Type: DRUG

Local radiotherapy

Local radiotherapy will be performed as per standard practice if indicated.

Intervention Type: RADIATION

Other Intervention Names

KEYTRUDA®; Biogaran Capecitabine

Eligibility Criteria

Inclusion Criteria

Patients eligible for this study must meet ALL of the following criteria:

1. Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent;

2. Subject ≥18 years of age on day of signing informed consent form (ICF);

3. Histologically proven TNBC defined as follows:

1. HER2 negativity (ASCO/CAP criteria)

2. AND less than 10% of cells stained by immunohistochemistry (IHC) for ER and PgR;

4. TNBC patients previously treated by standard neoadjuvant chemotherapy with a minimum of 6 cycles of immunochemotherapy containing pembrolizumab, per standard of care (and pembrolizumab label) and anthracyclines and/or taxanes (with/without carboplatin). Other drugs may be acceptable following discussion with the sponsor (with the exclusion of capecitabine);

5. Complete resection of the breast tumor(s) (and of any invaded lymph node);

6. No complete pathological response, defined as RCB Class I, II or III (per local assessment);

7. Available representative formalin-fixed paraffin-embedded (FFPE) tumor block from surgery specimen with its histological report;

8. Eastern Cooperative Oncology Group (ECOG) Performance Status <2;

9. Adequate organ and bone marrow function. All screening lab tests should be performed within 28 days before inclusion;

10. Resolution to at least grade 1 of all acute toxicities from previous therapies including immune-related toxicity due to pembrolizumab, except alopecia and grade 2 immune-related endocrinopathies controlled by hormone replacement which are allowed;

11. Minimal/maximal period for prior treatments (i.e. minimal delay from last dose of prior treatment to C1D1): breast surgery (the wound must have healed prior to C1D1) ≥2 weeks (maximum 10 weeks); last pembrolizumab injection ≥3 weeks;

12. Women of child-bearing potential must have a negative serum pregnancy test within 7 days before C1D1;

13. Women of child-bearing potential and male patients must agree to use 1 effective form of contraception from the time of the negative pregnancy test up to 6 months after the last dose of study drugs;

14. Patient should be able and willing to comply with study visits and procedures as per protocol;

15. Patients must be affiliated to a Social Security System (or equivalent).

Patients eligible for this study must not meet ANY of the following criteria:

1. Radiological or clinical evidence of metastatic disease documented by imaging or clinical examination performed during screening period;

2. Has received capecitabine or other ICI than pembrolizumab in the NAC regimen;

3. Has a known additional malignancy, excepted skin basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer or previously treated malignancy with no evidence of disease for ≥2 years;

4. Presents a contraindication to continue pembrolizumab treatment as per respective SmPC including known hypersensitivity;

5. Previous immune-related adverse event of any grade due to pembrolizumab that led to permanent discontinuation of pembrolizumab;

6. Presents a contraindication to capecitabine treatment as per SmPC (See EMA website for most recent edition of SmPC);

7. Complete DPD (Dihydropyrimidine Dehydrogenase) deficiency (a systematic screening of DPD deficiency must be performed);

8. Patient with active infection ;

9. Patients with history of uncontrolled or symptomatic cardiac disease ;

10. Patients having received brivudine within 4 weeks prior to inclusion;

11. Require the use of one of the following forbidden treatments during the study treatment period:

• Any investigational anticancer therapy other than the protocol specified treatment;
• Any concurrent chemotherapy, immunotherapy, biologic for cancer treatment, other than the ones stated in the protocol;

12. Pregnant women or women who are breast-feeding;

13. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons;

14. Persons deprived of their liberty or under protective custody or guardianship;

15. Participation in another therapeutic trial within the 30 days prior to randomization.

• CRITERIA FOR STANDARD OF CARE TREATED EXTERNAL COHORT

Patients eligible for this cohort must meet ALL of the following criteria:

1. Patient information prior to study entry and non-opposition to data collection

2. Subject ≥18 years of age ;

3. Histologically proven TNBC defined as follows:

1. HER2 negativity (ASCO/CAP criteria)

2. AND less than 10% of cells stained by immunohistochemistry (IHC) for ER and PgR;

4. TNBC patients previously treated by standard neoadjuvant chemotherapy with a minimum of 6 cycles of immunochemotherapy containing pembrolizumab, per standard of care (and pembrolizumab label) and anthracyclines and/or taxanes (with/without carboplatin). Other drugs may be acceptable following discussion with the sponsor (with the exclusion of capecitabine);

5. Complete resection of the breast tumor(s) (and of any invaded lymph node);

6. No complete pathological response, defined as RCB Class I, II or III (per local assessment);

7. Patient should have received at least one injection of pembrolizumab as post-surgery treatment (concomitantly or after radiotherapy).

Exclusion Criteria

Patients eligible for this study must not meet ANY of the following criteria:

1. Radiological or clinical evidence of metastatic disease documented by imaging or clinical examination after surgery.

2. Has received capecitabine or other ICI than pembrolizumab in the NAC regimen;

3. Has a known additional malignancy, excepted skin basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer or previously treated malignancy with no evidence of disease for ≥2 years;

4. Any investigational anticancer therapy (chemotherapy, immunotherapy, biologic for cancer treatment) other than pembrolizumab only as adjuvant treatment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UNICANCER

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Delphine LOIRAT, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Institut Curie Paris

Jean-Yves PIERGA, MD

Role: PRINCIPAL_INVESTIGATOR

Institut Curie Paris

Locations

CHU Amiens Picardie_Site Sud

Amiens, , France

Site Status: RECRUITING

Institut Sainte Catherine

Avignon, , France

Site Status: RECRUITING

Centre Hospitalier de la Côte Basque

Bayonne, , France

Site Status: RECRUITING

CHU Jean Minoz

Besançon, , France

Site Status: RECRUITING

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, , France

Site Status: RECRUITING

Centre François Baclesse

Caen, , France

Site Status: RECRUITING

Centre Georges-François Leclerc

Dijon, , France

Site Status: RECRUITING

CHD Vendee

La Roche-sur-Yon, , France

Site Status: RECRUITING

Centre Oscar Lambret

Lille, , France

Site Status: RECRUITING

Centre Léon Bérard

Lyon, , France

Site Status: RECRUITING

Institut Paoli-Calmettes

Marseille, , France

Site Status: RECRUITING

Institut Curie

Paris, , France

Site Status: RECRUITING

Clinique de La Croix du sud

Quint-Fonsegrives, , France

Site Status: RECRUITING

Institut Godinot

Reims, , France

Site Status: RECRUITING

Institut Curie

Saint-Cloud, , France

Site Status: RECRUITING

Clinique Mutualiste de l'Estuaire

Saint-Nazaire, , France

Site Status: RECRUITING

Centre Paul Strauss

Strasbourg, , France

Site Status: RECRUITING

Institut Claudius Regaud, IUCT Oncopole

Toulouse, , France

Site Status: RECRUITING

CHU Bretonneau

Tours, , France

Site Status: RECRUITING

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Telma ROQUE, PhD

Role: CONTACT

cappa@unicancer.fr

+33 (0) 1 80 50 12 92

Sylvie Mijonnet, PhD

Role: CONTACT

s-mijonnet@unicancer.fr

+33 (0) 1 44 23 04 65

Facility Contacts

Aurélie MOREIRA, MD

Role: primary

Moreira.Aurelie@chu-amiens.fr

Julien GRENIER

Role: primary

j.grenier@isc84.org

Thomas GRELLETY, MD

Role: primary

tgrellety@ch-cotebasque.fr

+335 59 44 37 62

Laura MANSI, MD

Role: primary

lmansi@chu-besancon.fr

Nadine DOHOLLOU, MD

Role: primary

n.dohollou@gor.bordeauxnord.com

George EMILE, MD

Role: primary

g.emile@baclesse.unicancer.fr

Sylvain LADOIRE, MD

Role: primary

sladoire@cgfl.fr

Camille GOISLARD DE MONSABERT, MD

Role: primary

camille.goislard-demonsabert@ght85.fr

+332 51 44 61 73

Claire CHEYMOL, MD

Role: primary

c-cheymol@o-lambret.fr

Olivier TREDAN, MD

Role: primary

olivier.tredan@lyon.unicancer.fr

Alexandre DE NONNEVILLE, MD

Role: primary

denonnevillea@ipc.unicancer.fr

Delphine LOIRAT, MD

Role: primary

delphine.loirat@curie.fr

+331 56 24 55 00

Francesco RICCI, MD

Role: primary

Ricci.onco@outlook.com

+335 32 02 72 44

Christelle JOUANNAUD, MD

Role: primary

christelle.jouannaud@reims.unicancer.fr

+333 26 50 43 83

LOIRAT, MD

Role: primary

delphine.loirat@curie.fr

+33147 11 15 15

Tifenne L'HARIDON, MD

Role: primary

tifenn.lharidon@hospigrandouest.fr

Thierry PETIT, MD

Role: primary

t.petit@icans.eu

MD

Role: primary

Dalenc.Florence@iuct-oncopole.fr

+335 31 15 51 22

Marie-Agnès BY, MD

Role: primary

MA.BY@chu-tours.fr

Anne KIEFFER, MD

Role: primary

a.kieffer@nancy.unicancer.fr

+333 83 59 85 64

Other Identifiers

2023-505291-30-01

Identifier Type: OTHER

Identifier Source: secondary_id

UC-BCG-2211

Identifier Type: -

Identifier Source: org_study_id