The Combination of Neoadjuvant Short-course Radiotherapy and Immunotherapy in Locally Advanced Rectal Cancer：A Open-label Single-arm Phase II Trial.
Overview
- Phase
- Phase 2
- Intervention
- PD-1 antibody
- Conditions
- Locally Advanced Rectal Cancer
- Sponsor
- Zhejiang Cancer Hospital
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- pCR rate
- Status
- Not Yet Recruiting
- Last Updated
- 5 years ago
Overview
Brief Summary
This is a single arm, open-label, prospective phase II clinical trial to evaluate the combination of neoadjuvant short-course radiotherapy and immunotherapy (PD-1 antibody) for patients with locally advanced rectal cancer (LARC). A total of 40 patients will be enrolled in this trial to receive 5*5Gy short-course radiotherapy, followed by 4 cycles of CAPOX chemotherapy and PD-1 antibody. Then they will receive the TME surgery and another 4 cycles of CAPOX chemotherapy. There are two cohorts according to the microsatellite instability status: (1) the micro-satellite stable (MSS) cohort（n=32), (2) the MSI-high cohort (n=8). The primary end point is the rate of pathological complete response (pCR). The long-term prognosis and adverse effects will also be evaluated and analyzed.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Pathological confirmed rectal adenocarcinoma and the distance from anal verge less than 12 cm;
- •Clinical stage T3-4 and/or N+ (AJCC 8th);
- •No distant metastases;
- •Age 18-70 years old, female and male;
- •No previous chemotherapy, radiotherapy, immunotherapy or other anti-tumor treatment;
- •Adequate organ function defined at baseline as:
- •ANC ≥1.5×109 /L，PLt ≥75×109 /L，Hb ≥90 g/L;
- •TBIL ≤1.5×ULN, ALT ≤2.5ULN, AST ≤2.5ULN, BUN and Cr ≤1×ULN or Ccr ≥50ml/min (Cockcroft-Gault formula);
- •INR ≤1.5×ULN or PT ≤1.5×ULN (If the patient is receiving anticoagulant therapy, PT should be within the intended use range of the anticoagulant drug);
- •With good compliance and no serious comorbidity;
Exclusion Criteria
- •History of other uncured malignancies within 5 years. Cured tumor with good prognosis, such as skin basal cell carcinoma, cervical cancer and superficial bladder cancer, will be excluded;
- •Have received surgery within 4 weeks before the enrollment;
- •History of obstruction within 6 months before the enrollment;
- •History of active autoimmune disease, interstitial lung disease, epilepsy and dysphrenia;
- •With uncontrolled cardiovascular disease: active coronary heart disease; grade III-IV cardiac insufficiency according to the NYHA criteria; and myocardial infarction within 1 year;
- •With active infection or fever of \>38.5 ℃ with unknown cause (tumor-induced fever judged could be enrolled);
- •DPD deficiency;
- •Allergic to any component of chemotherapy or immunotherapy;
- •With congenital or acquired immunodeficiency (such as those with HIV infection), active hepatitis B or hepatitis C;
- •Usage of corticosteroids (prednison dose of \> 10 mg/day) or other immunosuppressors for systemic treatment within the first 14 days of research;
Arms & Interventions
Neoadjuvant short-course radiotherapy+immunotherapy+chemotherapy
A total of 40 patients receive 5\*5Gy short-course radiotherapy, followed by 4 cycles of CAPOX chemotherapy and PD-1 antibody, finally receive the TME surgery and another 4 cycles of CAPOX chemotherapy. Interventions: Shor-course radiotherapy: 25Gy/5Fx; Induction immunotherapy: Sintilimab 200mg ivgtt d1 q3w x 4 cycles; Concurrent Chemotherapy: Oxaliplatin: 130mg/m2 d1 q3w + Capecitabine: 1000mg/m2 d1-14 q3w x 4 cycles;
Intervention: PD-1 antibody
Neoadjuvant short-course radiotherapy+immunotherapy+chemotherapy
A total of 40 patients receive 5\*5Gy short-course radiotherapy, followed by 4 cycles of CAPOX chemotherapy and PD-1 antibody, finally receive the TME surgery and another 4 cycles of CAPOX chemotherapy. Interventions: Shor-course radiotherapy: 25Gy/5Fx; Induction immunotherapy: Sintilimab 200mg ivgtt d1 q3w x 4 cycles; Concurrent Chemotherapy: Oxaliplatin: 130mg/m2 d1 q3w + Capecitabine: 1000mg/m2 d1-14 q3w x 4 cycles;
Intervention: Capecitabine
Neoadjuvant short-course radiotherapy+immunotherapy+chemotherapy
A total of 40 patients receive 5\*5Gy short-course radiotherapy, followed by 4 cycles of CAPOX chemotherapy and PD-1 antibody, finally receive the TME surgery and another 4 cycles of CAPOX chemotherapy. Interventions: Shor-course radiotherapy: 25Gy/5Fx; Induction immunotherapy: Sintilimab 200mg ivgtt d1 q3w x 4 cycles; Concurrent Chemotherapy: Oxaliplatin: 130mg/m2 d1 q3w + Capecitabine: 1000mg/m2 d1-14 q3w x 4 cycles;
Intervention: Oxaliplatin
Outcomes
Primary Outcomes
pCR rate
Time Frame: The TME surgery will be recommended at 1 week after the neoadjuvant therapy. The pCR rate is evaluated after surgery. Assessed up to 6 months
Pathologic complete response rate
Secondary Outcomes
- Surgical complications(Assessed up to 3 years from the TME surgery)
- Quality of Life Scale(Assessed up to 5 years)
- 3-year DFS(Assessed up to 3 years)
- 3-year local recurrence rate(Assessed up to 3 years)
- 3-year OS(Assessed up to 3 years)
- Grade 3-4 adverse effects rate(Assessed up to 3 years)