A Phase II Study of Total Neoadjuvant Chmoradiation Treatment Plus SHR1210 for High-risk Locally Advanced Rectal Cancer and Biomarker Screening Base on Neoantigen
Overview
- Phase
- Phase 2
- Intervention
- SHR-1210
- Conditions
- Rectal Cancer
- Sponsor
- Peking University Cancer Hospital & Institute
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- pathologic complete response rate(pCR rate)
- Last Updated
- 5 years ago
Overview
Brief Summary
This study is designed to test the efficacy and safety of Total Neoadjuvant Treatment plus SHR1210（an anti-PD-1 Inhibitor) for High-risk locally advanced Rectal Cancer, Meanwhile, screening effective Biomarker base on neoantigen.
Detailed Description
The combined treatment model of neoadjuvant chemoradiotherapy treatment + radical rectal resection + adjuvant therapy has become the standard treatment model for locally advanced mid-low rectal cancer, However, the existing evidence shows that this comprehensive treatment method has reached the upper limit of efficacy and cannot continue to reduce the metastatic rate and improve the survival rate. Recent studies have shown that PD-1 antibody inhibitors have excellent curative effects on the treatment of a variety of tumors and have good safety. This study is a single-arm, single-center, prospective, phase II clinical study. It is designed to test the efficacy and safety of Total Neoadjuvant chmoradiation Treatment plus SHR1210 for High-risk locally advanced Rectal Cancer, Meanwhile, screening effective Biomarker base on neoantigen. In this study, patients with high-risk rectal cancer will receive 3 cycles induction CapeOX and SHR-1210, intensity modulated radiotherapy with concurrent capecitabine and 2 cycles consolidation CapeOX and total mesorectal excision. This study is designed to recruit 25 patients in all.
Investigators
Aiwen Wu
Chief, Unit III & Ostomy Service, Gastrointestinal Cancer center
Peking University Cancer Hospital & Institute
Eligibility Criteria
Inclusion Criteria
- •Age ≥ 18 years and ≤70 years.
- •ECOG Performance status 0-
- •Histologically confirmed diagnosis of adenocarcinoma of the rectum.
- •The distance from down verge of tumor to anal-rectal junction (ARJ) ≤8cm, or ≤12 cm based on sigmoidoscopy.
- •Clinical Stage T3c, T3d, T4a or T4b, or EMVI (+) or mrN2 or MRF (+) based on MRI.
- •No evidence of distant metastases.
- •No prior pelvic radiation therapy.
- •No prior chemotherapy or surgery for rectal cancer.
- •No active infections requiring systemic antibiotic treatment.
- •No systemic infection requiring antibiotic treatment.
Exclusion Criteria
- •Recurrent rectal cancer.
- •Anticipated unresectable tumor after neoadjuvant treatment.
- •Patients with a history of a prior malignancy within the past 5 years, except for adequately treated basal cell or squamous cell skin cancer.
- •Patients with a history of any arterial thrombotic event within the past 6 months. This includes angina (stable or unstable), MI, TIA, or CVA.
- •Other Anticancer or Experimental Therapy.
- •Women who are pregnant or breast-feeding.
- •Patients with any other concurrent medical or psychiatric condition or disease which would make them inappropriate candidates for entry into this study.
- •Patients with a history of anti-PD-1, anti-PD-L1, anti-PD-L2 or CEGFR TKI therapy.
- •Patients underwent major surgery or had not recovered from the side effects of this surgery, received a vaccine, received immunotherapy within 4 weeks before the first use of the study drug, and received radiotherapy within 2 weeks.
- •Patients who received hematopoietic stimulating factors therapy, such as G-CSF and erythropoietin, within 1 week before the first administration of the study drug.
Arms & Interventions
TNT+SHR1210
Patients with high-risk locally advanced rectal cancer will receive chemotherapy and SHR-1210 before chemoradiaton, after chemoradiaton, patient will receive consolidation chemotherapy. This arm is called Total Neoadjuvant Treatment (TNT) plus SHR-1210. The neoadjuvant chemotherapy regimen is designed as 3 cycles of CapeOX ( Capecitabine + Oxaliplatin ) plus SHR-1210 over a period of approximately 8 weeks. Tumor response will be evaluated after chemotherapy. Then patients will undergo 22f-IMRT (Intensity modulated radiotherapy) with capecitabine. Patients will receive two more cycles of consolidation CapeOX if tolerable when there was no progressed disease in induction CapeOX. Finally, patients will receive TME (Total mesorectal excision) following TNT+SHR1210 if no metastasis occurs.
Intervention: SHR-1210
TNT+SHR1210
Patients with high-risk locally advanced rectal cancer will receive chemotherapy and SHR-1210 before chemoradiaton, after chemoradiaton, patient will receive consolidation chemotherapy. This arm is called Total Neoadjuvant Treatment (TNT) plus SHR-1210. The neoadjuvant chemotherapy regimen is designed as 3 cycles of CapeOX ( Capecitabine + Oxaliplatin ) plus SHR-1210 over a period of approximately 8 weeks. Tumor response will be evaluated after chemotherapy. Then patients will undergo 22f-IMRT (Intensity modulated radiotherapy) with capecitabine. Patients will receive two more cycles of consolidation CapeOX if tolerable when there was no progressed disease in induction CapeOX. Finally, patients will receive TME (Total mesorectal excision) following TNT+SHR1210 if no metastasis occurs.
Intervention: Oxaliplatin
TNT+SHR1210
Patients with high-risk locally advanced rectal cancer will receive chemotherapy and SHR-1210 before chemoradiaton, after chemoradiaton, patient will receive consolidation chemotherapy. This arm is called Total Neoadjuvant Treatment (TNT) plus SHR-1210. The neoadjuvant chemotherapy regimen is designed as 3 cycles of CapeOX ( Capecitabine + Oxaliplatin ) plus SHR-1210 over a period of approximately 8 weeks. Tumor response will be evaluated after chemotherapy. Then patients will undergo 22f-IMRT (Intensity modulated radiotherapy) with capecitabine. Patients will receive two more cycles of consolidation CapeOX if tolerable when there was no progressed disease in induction CapeOX. Finally, patients will receive TME (Total mesorectal excision) following TNT+SHR1210 if no metastasis occurs.
Intervention: Capecitabine
TNT+SHR1210
Patients with high-risk locally advanced rectal cancer will receive chemotherapy and SHR-1210 before chemoradiaton, after chemoradiaton, patient will receive consolidation chemotherapy. This arm is called Total Neoadjuvant Treatment (TNT) plus SHR-1210. The neoadjuvant chemotherapy regimen is designed as 3 cycles of CapeOX ( Capecitabine + Oxaliplatin ) plus SHR-1210 over a period of approximately 8 weeks. Tumor response will be evaluated after chemotherapy. Then patients will undergo 22f-IMRT (Intensity modulated radiotherapy) with capecitabine. Patients will receive two more cycles of consolidation CapeOX if tolerable when there was no progressed disease in induction CapeOX. Finally, patients will receive TME (Total mesorectal excision) following TNT+SHR1210 if no metastasis occurs.
Intervention: Intensity modulated radiotherapy
TNT+SHR1210
Patients with high-risk locally advanced rectal cancer will receive chemotherapy and SHR-1210 before chemoradiaton, after chemoradiaton, patient will receive consolidation chemotherapy. This arm is called Total Neoadjuvant Treatment (TNT) plus SHR-1210. The neoadjuvant chemotherapy regimen is designed as 3 cycles of CapeOX ( Capecitabine + Oxaliplatin ) plus SHR-1210 over a period of approximately 8 weeks. Tumor response will be evaluated after chemotherapy. Then patients will undergo 22f-IMRT (Intensity modulated radiotherapy) with capecitabine. Patients will receive two more cycles of consolidation CapeOX if tolerable when there was no progressed disease in induction CapeOX. Finally, patients will receive TME (Total mesorectal excision) following TNT+SHR1210 if no metastasis occurs.
Intervention: Total mesorectal excision
Outcomes
Primary Outcomes
pathologic complete response rate(pCR rate)
Time Frame: 1 month after surgery
The number of patients with pCR divided by the total number of patients
Secondary Outcomes
- Toxicity of TNT+SHR-1210(90 days after neoadjuvant treatment)
- Disease-free survival (DFS)(3 years)
- Change of TCR repertoire(1 week before surgery)
- Surgical complication rate(30 days after surgery)
- Major adverse events(90 days after the last use of SHR-1210)