Adjuvant PD-1 Blockade for High-risk Stage-II DMMR/MSI-H Colorectal Cancer
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Tislelizumab, Adjuvant chemotherapy.
- Who it may be relevant to
- Registry conditions: Colorectal Cancer, Microsatellite Instability High. Basic parameters: 18 years — 80 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- China
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Short-course PD-1 Blockade As Adjuvant Treatment for High-risk Stage-II DMMR/MSI-H Colorectal Cancer
Overview
This open-label phase III trial investigates the efficacy of two cycles of PD-1 blockade (Tislelizumab) as adjuvant therapy to see how it works compared with standard of care (SOC) in treating patients with stage II dMMR/MSI-H colorectal cancer. The rational of giving PD-1 blockade as adjuvant therapy is based on the fact that tumor recurrence is extremely low among patients receiving neoadjuvant immunotherapy, which suggests that PD-1 blockade may likely improve patients' long-term survival. As for the short course (two cycles), we have the following considerations: firstly, the NICHE-2 trial, which adopted a two-cycle regimen, reported no recurrences during follow-up, suggesting that short-course anti-PD-1 therapy may be sufficient to improve the survival of patients with localized dMMR/MSI-H colorectal cancer. Secondly, the potential benefits of PD-1 blockade should be balanced against its toxicities, because patients with stage-II dMMR colorectal cancer generally have a good prognosis. Two cycles of PD-1 blockade have been shown to have a good safety profile, with low incidence of grade 3-4 and immune-related adverse events.
Detailed description
This is an open-label, multi-centre, randomised, phase III trial comparing the combination of PD-1 blockade + SOC versus SOC alone as adjuvant therapy for patients with high-risk stage-II dMMR/MSI-H colorectal cancer.
Primary Objective: To determine whether the addition of Tislelizumab can significantly improve disease-free survival (DFS) compared to standard of care in patients with high-risk stage-II colorectal cancer.
Secondary objectives:
* To determine whether the addition of Tislelizumab can significantly improve overall survival (OS) compared to standard of care * To assess the adverse events (AE) profile (including immune-related adverse events, ir-AEs).
OUTLINE: Patients are randomized to 1 of 2 arms, stratified by cT4 status.
Arm 1 (experimental group): patients receive Tislelizumab 200mg intravenously on day 1, with or without adjuvant chemotherapy, and repeat the treatment on day 22. Patients undergo routine follow-up every 3 months for the first 3 years, and then every 6 months for the year 4-5.
Arm 2 (control group): patients receive standard of care (SOC), whether with surveillance alone, single-agent Capecitabine, or CapeOx/FOLFOX, at the discretion of the doctor in charge. Patients undergo routine follow-up every 3 months for the first 3 years, and then every 6 months for the year 4-5.
Statistics According to the statistical design, 180 patients (90 per arm) are to be randomized. The study is expected to take up to 36 months to complete accrual.
Interventions
- Drug Tislelizumab
\- Tislelizumab 200mg (day 1 and day 22), administered after surgery - Drug Adjuvant chemotherapy
* Adjuvant therapy is not mandatory. * Optional adjuvant regimens include FOLFOX, CapeOX, 5-FU+LV, or Capecitabine.
Primary outcome measures
- Disease-free survival (DFS) [Time frame: 3 years]
Secondary outcome measures (2)
- Overall survival (OS) [Time frame: 5 years]
- Incidence of adverse events [Time frame: up to 30 days after last treatment]
Eligibility criteria
Inclusion criteria
- dMMR and/or MSI-H colorectal carcinoma that undergo surgical resection
- Pathologically confirmed as stage II (T3-4,N0), with at least one of the following risk factors: 1) T4 (including T4a and T4b); 2) Vascular invasion; 3) Perineural invasion; 4) Poor differentiation (including mucinous and signet-ring carcinoma); 5) Obstruction and/or perforation before surgery.
- Perioperative CT/MR/PET-CT find no signs of metastases
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days prior to study start
- Aged 18-80
- No prior medical therapy (chemotherapy, immunotherapy, biologic or targeted therapy) or radiation therapy for the current cancer
- Adequate organ function
Exclusion criteria
- Active autoimmune disease that has required systemic treatment in past 2 years
- Positive surgical margin (R1/R2 resection)
- Presence of post-operative complications that may preclude treatment
- Active infection requiring systemic therapy
- Any other malignant disease within the preceding 5 years with the exception of non-melanomatous skin cancer, carcinoma in situ and early stage disease with a recurrence risk <5%.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
China · 1 center
- Dept. of Colorectal Surgery, Sun Yat-sen University Cancer Center. Yuexiu District, Dongfe — Guangzhou
Identifiers
NCT: NCT06520683 · 2024-FXY-219