CAPECITABINE (capecitabine) for Triple negative breast cancer | Residual disease after neoadjuvant chemo-immunotherapy

Inclusion criteria

• {"criterion_text":"- Experimental arm : 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;\n- Experimental arm : 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);\n- Experimental arm : Complete resection of the breast tumor(s) (and of any invaded lymph node);\n- Experimental arm : No complete pathological response, defined as RCB Class I, II or III (per local assessment);\n- Experimental arm : Available representative formalin-fixed paraffin-embedded (FFPE) tumor block from surgery specimen with its histological report;\n- Experimental arm : Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2;\n- Experimental arm : Adequate organ and bone marrow function. All screening lab tests should be performed within 28 days before randomization;\n- External Cohort : Patient information prior to study entry and non-opposition to data collection\n- External Cohort : Subject ≥18 years of age ;\n- External Cohort : Histologically proven TNBC defined as follows: a. HER2 negativity (ASCO/CAP criteria) b. AND less than 10% of cells stained by immunohistochemistry (IHC) for ER and PgR;\n- External Cohort : 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);\n- Experimental arm : 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;\n- External Cohort : Complete resection of the breast tumor(s) (and of any invaded lymph node);\n- External Cohort : No complete pathological response, defined as RCB Class I, II or III (per local assessment);\n- External Cohort : Patient should have received at least one injection of pembrolizumab as post-surgery treatment (concomitantly or after radiotherapy).\n- Experimental arm : 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;\n- Experimental arm : Women of child-bearing potential must have a negative serum pregnancy test within 7 days before C1D1;\n- Experimental arm : 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 4 months after the last dose of study drugs;\n- Experimental arm : Patient should be able and willing to comply with study visits and procedures as per protocol;\n- Experimental arm : Patients must be affiliated to a Social Security System (or equivalent).\n- Experimental arm : Subject ≥18 years of age on day of signing informed consent form (ICF);\n- Experimental arm : Histologically proven TNBC defined as follows: a. HER2 negativity (ASCO/CAP criteria) b. AND less than 10% of cells stained by immunohistochemistry (IHC) for ER and PgR;"}

Exclusion criteria

• {"criterion_text":"- Experimental arm : Radiological or clinical evidence of metastatic disease documented by imaging or clinical examination performed during screening period;\n- Experimental arm : Patients having received brivudine within 4 weeks prior to inclusion;\n- Experimental arm : 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;\n- Experimental arm : Pregnant women or women who are breast-feeding;\n- Experimental arm : Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons;\n- Experimental arm : Persons deprived of their liberty or under protective custody or guardianship;\n- Experimental arm : Participation in another therapeutic trial within the 30 days prior to randomization.\n- External Cohort : Radiological or clinical evidence of metastatic disease documented by imaging or clinical examination after surgery.\n- External Cohort : Has received capecitabine or other ICI than pembrolizumab in the NAC regimen;\n- External Cohort : 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;\n- External Cohort : Any investigational anticancer therapy (chemotherapy, immunotherapy, biologic for cancer treatment) other than pembrolizumab only as adjuvant treatment.\n- Experimental arm : Has received capecitabine or other ICI than pembrolizumab in the NAC regimen;\n- Experimental arm : 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;\n- Experimental arm : Presents a contraindication to continue pembrolizumab treatment as per respective SmPC including known hypersensitivity;\n- Experimental arm : Previous immune-related adverse event of any grade due to pembrolizumab that led to permanent discontinuation of pembrolizumab;\n- Experimental arm : Presents a contraindication to capecitabine treatment as per SmPC (See EMA website for most recent edition of SmPC);\n- Experimental arm : Complete DPD (Dihydropyrimidine Dehydrogenase) deficiency (a systematic screening of DPD deficiency must be performed);\n- Experimental arm : Patient with active infection ;\n- Experimental arm : Patients with history of uncontrolled or symptomatic cardiac disease ;"}

Primary endpoints

• {"endpoint_text":"- 2-year Invasive disease free survival (iDFS).","definition_or_measurement_approach":"iDFS at 2 years as assessed by investigator (invasive disease-free survival over 2 years)."}

Secondary endpoints

• {"endpoint_text":"- Efficacy: Overall Survival (OS) is defined as the time from the date of inclusion to the date of death due to any cause. For patients alive, OS will be censored at date of last contact.","definition_or_measurement_approach":"OS defined as time from inclusion to death from any cause; censoring at last contact for alive patients."}
• {"endpoint_text":"- Efficacy: Distant disease-free survival (DDFS) is defined as the time from the date of inclusion to the date of distant relapse or death due to any cause. For patients alive without distant relapse, DDFS will be censored at date of last contact.","definition_or_measurement_approach":"DDFS defined as time from inclusion to distant relapse or death; censoring at last contact for alive patients without distant relapse."}
• {"endpoint_text":"- Efficacy : iDFS, OS and DDFS will also be compared to the external cohort of TNBC patients without pCR after NAC and treated with adjuvant pembrolizumab as part of standard of care after surgery","definition_or_measurement_approach":"Comparative analysis of iDFS, OS and DDFS versus an external cohort of TNBC patients treated with adjuvant pembrolizumab (standard of care)."}
• {"endpoint_text":"- Safety : Safety and tolerability assessed by Adverse Events (AEs) as per the National Cancer Institute Common Toxicity Criteria for Adverse Events version 5.0 (CTCAE v5.0).","definition_or_measurement_approach":"Safety assessed by recording AEs and grading per NCI CTCAE v5.0."}

France

Earliest CTIS Part Ii Submission Date

21-10-2024

Latest Decision Or Authorization Date

14-11-2024

Processing Time Days

24

Number Of Sites

25

Number Of Participants

220

Primary sponsor

Full Name

Unicancer

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France