CAPECITABINE for Triple-negative breast cancer (early)

Stratification factors

• Homologous Repair Deficiency (HRD) status

Inclusion criteria

• {"criterion_text":"-Signed written informed consent approved by the Ethical Review Board (IRB)."}
• {"criterion_text":"-Willingness of female patients of childbearing potential, male patients and their sexual partners to use an effective means of contraception during the treatment period and at least 6 months thereafter."}
• {"criterion_text":"-Willingness by the patient to undergo treatment and study related procedures according to the protocol."}
• {"criterion_text":"-Age ≥ 18 to < 76 years."}
• {"criterion_text":"-Histologically confirmed unilateral adenocarcinoma of the breast where neoadjuvant chemotherapy followed by definitive surgery is planned."}
• {"criterion_text":"-Node positive disease (N1-3) or if clinically N0 Tumor over 20 mm."}
• {"criterion_text":"-ER negative tumor defined by at least one the following: a. ER < 1% cells positive by immunohistochemistry (IH.C) or ER < 10% cells positive by IHC and basal-like subtype using gene expression analysis b. ER < 10% cells positive by IHC and < 10% cells positive by IHC."}
• {"criterion_text":"-HER2-normal tumor defined according to applicable national guidelines."}
• {"criterion_text":"-Consent for germline mutation screening for BRCA1, BRCA2 and other inherited breast cancer associated genes."}
• {"criterion_text":"-WHO performance status 0 or 1."}
• {"criterion_text":"-Negative pregnancy test in women of childbearing potential (premenopausal or <12 months of amenorrhea post-menopause and who have not undergone surgical sterilization)."}

Exclusion criteria

• {"criterion_text":"-Clinical or radiological signs of metastatic disease."}
• {"criterion_text":"-History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or non-melanoma skin cancer."}
• {"criterion_text":"-Previous chemotherapy for cancer or other malignant disease."}
• {"criterion_text":"-Charlson comorbidity index, excluding score for malignancy: (CCI) > 2, Comment: In patients 70-75 a CCI = 3 is allowed, see appendix B."}
• {"criterion_text":"-Inadequate organ function, suggested by the following laboratory results: a Absolute neutrophil count < 1,5 x 109/L b Platelet count < 100 x 109/L c Haemoglobin < 90 g/L d Total bilirubin greater than the upper limit of normal (ULN) unless the patient has documented Gilbert´s syndrome e ASAT (SGOT) and/or ALAT (SGPT) > 2,5 x ULN f ASAT (SGOT) and/or ALAT (SGPT) > 1,5 x ULN with concurrent serum alkaline phosphatase (ALP) > 2,5 x ULN g Serum creatinine clearance < 50 ml/min"}
• {"criterion_text":"-Concurrent peripheral neuropathy of grade 3 or greater (NCI-CTCAE, Version 5.0)"}
• {"criterion_text":"-Patient who is actively breast feeding."}
• {"criterion_text":"-Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol."}
• {"criterion_text":"-Patients with known deficiency of the DPD-enzyme who completely lack DPD."}

Primary endpoints

• {"endpoint_text":"-pCR with the addition of capecitabine compared with carboplatin-based chemotherapy alone.","definition_or_measurement_approach":"Pathologic complete response (pCR) rate assessed after preoperative chemotherapy (as stated in the main objective)."}

Secondary endpoints

• {"endpoint_text":"-Invasive Disease Survival (IDFS) with the addition of capecitabine compared with carboplatin-based chemotherapy alone.","definition_or_measurement_approach":"Comparison of invasive disease-free survival between treatment arms (time-to-event endpoint as described)."}
• {"endpoint_text":"-Breast Cancer Specific Survival (BCSS) with the addition of capecitabine compared with carboplatin-based chemotherapy alone.","definition_or_measurement_approach":"Comparison of breast cancer specific survival between treatment arms (time-to-event endpoint)."}
• {"endpoint_text":"-Overall Survival (OS) with the addition of capecitabine compared with carboplatin-based chemotherapy alone.","definition_or_measurement_approach":"Comparison of overall survival between treatment arms (time-to-event endpoint)."}

Other endpoints

• {"endpoint_text":"-To compare invasive disease free (IDFS), breast cancer specific survival (BCSS), distant recurrence free survival (DRFS), and overall survival (OS).","definition_or_measurement_approach":"Survival and recurrence endpoints compared between arms; time-to-event analyses."}
• {"endpoint_text":"-To evaluate the tolerability defined by toxicity and dose intensity.","definition_or_measurement_approach":"Assessment of adverse events/toxicity (NCI-CTCAE) and dose intensity metrics."}
• {"endpoint_text":"-To determine the pCR rates in different treatment arms stratified for Homologous Repair Deficiency (HRD) positive vs. HRD-negative/HRDintermediate.","definition_or_measurement_approach":"pCR rate evaluated within biomarker-defined subgroups based on HRD status."}
• {"endpoint_text":"-To characterize different subsets of TNBC in terms of morphology, epigenetic alterations as well as somatic and inherited genetic alterations.","definition_or_measurement_approach":"Molecular and pathological characterization of tumor subsets (exploratory analyses)."}
• {"endpoint_text":"-To determine the pCR rate and long-term outcome in subsets of TNBC with defined molecular genetic alterations including BRCA1, BRCA2 and PALB2 germline mutations and others, BRCA1, BRCA2 and PALB2 somatic mutations and others and BRCA1 or RAD51 promoter metylation.","definition_or_measurement_approach":"Subset analyses of pCR and long-term outcomes in molecularly defined groups (exploratory)."}

Sweden

Earliest CTIS Part Ii Submission Date

15-05-2024

Latest Decision Or Authorization Date

07-10-2024

Processing Time Days

145

Number Of Sites

15

Number Of Participants

245

Denmark

Earliest CTIS Part Ii Submission Date

15-05-2024

Latest Decision Or Authorization Date

08-07-2025

Processing Time Days

419

Number Of Sites

6

Number Of Participants

80

Primary sponsor

Full Name

Region Skåne

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Sweden