A Randomized, Double-blind, Placebo-controlled, Phase III Study to Evaluate the Efficacy and Safety of Camrelizumab and Capecitabine Versus Capecitabine as Adjuvant Therapy in Early-stage Triple-negative Breast Cancer Patients With Tertiary Lymphoid Structure in Tumor Who Have Residual Tumor in the Breast or Axillary Lymph Nodes Following Neoadjuvant Chemotherapy.
Overview
- Phase
- Phase 3
- Intervention
- Carrellizumab + Capecitabine
- Conditions
- Breast Neoplasms
- Sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Enrollment
- 375
- Locations
- 1
- Primary Endpoint
- Disease-Free Survival
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This study aims to evaluate the efficacy and safety of camrelizumab in combination with capecitabine compared to placebo in combination with capecitabine as adjuvant therapy for patients with triple-negative breast cancer (TNBC) who have not achieved pathological complete response (pCR) after neoadjuvant chemotherapy and have tertiary lymphoid structures (TLS) in the tumor tissue. The primary endpoint of this study is disease-free survival (DFS) to assess the long-term effectiveness of the treatment. Secondary endpoints include invasive disease- free survival (IDFS), overall survival (OS), distant recurrence-free interval (DRFI), as well as safety and patient-reported outcomes. These endpoints will comprehensively evaluate the effectiveness of the treatment and the overall survival status of the patients.
The study anticipates a total sample size of 375 patients, who will be randomly assigned to either the experimental group or the control group. The experimental group will receive 8 cycles of adjuvant therapy of capecitabine and camrelizumab. The control group will receive 8 cycles of adjuvant therapy with capecitabine and placebo. This study aims to investigate whether non-pcr breast cancer patients with TLS in tumors can benefit from the adjuvant immunotherapy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed informed consent form.
- •Female patients aged ≥18 years at the time of signing informed consent.
- •Patients with adequate cognitive ability and willingness to understand and comply with the treatment and follow-up plans as required by the study protocol.
- •Confirmed invasive breast cancer on histological examination.
- •Clinical stage at presentation: cT4/any N/M0, any cT/N2-3/M0, or cT1-3/N0-1/M0 (patients with cT1mi/T1a/T1b/N0 are not eligible).
- •Confirmation of TNBC diagnosis and TLS and PD-L1 status through central examination of representative tumor tissue specimens resected during surgery.
- •Patients with synchronous bilateral invasive disease or multicentric tumors (involving more than one quadrant) are eligible for the study, provided that all discrete lesions are confirmed by the central laboratory as TNBC and TLS-positive. For patients with multifocal tumors (more than one mass involving the same quadrant), sampling must be performed on at least one lesion, confirmed by the central laboratory as TNBC and TLS-positive.
- •For patients with multifocal or multicentric breast cancer, measurement of the largest lesion to determine the T stage is required.
- •Confirmation of TNBC and prospective assessment of TLS presence in tumor tissue before study enrollment, confirmed by HE staining and immunofluorescence staining. TLS positivity is defined as the presence of CD3+ and CD20+ cell aggregates identified by HE staining or immunofluorescence staining on tumor tissue or peritumoral tissue sections.
- •Completion of preoperative systemic chemotherapy and camrelizumab treatment.
Exclusion Criteria
- •Stage IV (metastatic) breast cancer
- •Inadequate resection (as described in the inclusion criteria)
- •At the end of preoperative systemic therapy, the overall response assessment by the researchers resulted in disease progression.
- •Patients recommended for radiotherapy for breast cancer but contraindicated due to medical reasons (e.g., connective tissue diseases or prior radiation to the ipsilateral breast).
- •Presence of another malignant tumor within the last 5 years before screening (excluding appropriately treated cervical carcinoma in situ, non-melanoma skin cancer, Stage I endometrial carcinoma, or DCIS).
- •Prior use of CD137 agonists or immune checkpoint inhibitors, including anti-cytotoxic T-lymphocyte-associated protein 4, anti-PD-1, and anti-PD-L1 therapeutic antibodies.
- •Current presence of ≥ Grade 2 peripheral neuropathy (according to NCI CTCAE v5.0).
- •Dyspnea at rest.
- •Presence of any of cardiopulmonary dysfunction.
- •Current or past history of autoimmune disease or immunodeficiency.
Arms & Interventions
Camrelizumab group
Intervention: Carrellizumab + Capecitabine
Placebo group
Intervention: Placebo + Capecitabine
Outcomes
Primary Outcomes
Disease-Free Survival
Time Frame: 3 years
Time from randomization to the first occurrence of any of the following events: local recurrence, distant metastasis, contralateral breast cancer, or death from any cause.
Secondary Outcomes
- Patient-reported outcomes-EORTC QLQ-C30 scores after treatment(3 years)
- Patient-reported outcomes-EORTC QLQ-C30 scores changes(3 years)
- Invasive Disease-Free Survival(3 years)
- Overall Survival(3 years)
- Distant Recurrence-Free Interval(3 years)
- Patient-reported outcomes-Proportion of patients in each group experiencing clinically meaningful deterioration(3 years)