Study Of Capecitabine Combined With Camrelizumab For Non-pCR TNBC With TLS After Neoadjuvant Chemoterapy

NCT06313463 | Recruiting Phase 3

• 1 other identifier: SYSKY-2023-1282-02
• Study Type: interventional
• Target: 375
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Neoplasms

Outcome Measures

Primary Outcomes (1)

• Disease-Free Survival

  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.

  3 years

Secondary Outcomes (6)

• 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

• Patient-reported outcomes-EORTC QLQ-C30 scores after treatment

  3 years

Study Arms (2)

Camrelizumab group

EXPERIMENTAL

Drug: Carrellizumab + Capecitabine

Placebo group

PLACEBO COMPARATOR

Drug: Placebo + Capecitabine

Interventions

Carrellizumab + Capecitabine DRUG

Capecitabine 1000-1250mg/m2 PO bid D1-14（Q3W）+ Carrellizumab 200mg IV D1（Q3W），8 cycles in total

Camrelizumab group

Placebo + Capecitabine DRUG

Capecitabine 1000-1250mg/m2 PO bid D1-14（Q3W）+ Placebo 200mg IV D1（Q3W），8 cycles in total

Placebo group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Pathological assessment after neoadjuvant treatment did not achieve pCR.
• Adequate resection: Complete removal of all clinically evident lesions in the breast and lymph nodes.
• Interval between the date of initial surgery and randomization date not exceeding 12 weeks.
• Eastern Cooperative Oncology Group performance status score of 0 or 1.
• Completion of neoadjuvant therapy with echocardiography or multi-gated acquisition scan showing left ventricular ejection fraction (LVEF) ≥50% during the screening period and an absolute decrease in LVEF compared to pre-chemotherapy LVEF not exceeding 15%. Alternatively, if LVEF assessment was not performed pre-chemotherapy, LVEF must be ≥55% during the screening period post-neoadjuvant therapy.

You may not qualify if:

• Stage IV (metastatic) breast cancer
• 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.
• Idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonia, or history of idiopathic pneumonia or evidence of active pneumonia.
• Active tuberculosis.
• History of severe, uncontrolled systemic diseases (e.g., clinically significant cardiovascular, pulmonary, or metabolic diseases; impaired wound healing; ulcers).
• Known active liver disease, such as autoimmune hepatitis or sclerosing cholangitis.
• Receipt of major surgery within 4 weeks before randomization (excluding breast cancer surgery) or anticipated need for major surgery during the study.
• Occurrence of severe infection within 4 weeks before randomization, including but not limited to hospitalization due to complications of infection, sepsis, or severe pneumonia, SARS-CoV-2 infection, or any active infection deemed likely to affect patient safety by the investigator.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Study Sites (1)

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510120, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Shicheng Su

  Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shicheng Su

CONTACT

+86 13631304227; sushch@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2024
• First Posted: March 15, 2024
• Study Start: March 1, 2024
• Primary Completion (Estimated): September 1, 2031
• Study Completion (Estimated): December 1, 2035
• Last Updated: March 15, 2024

Record last verified: 2024-03

Locations

CN (1)