Toripalimab Combined With Neoadjuvant Chemoradiotherapy as First-line Treatment for Locally Advanced，High-Risk，MSS Rectal Cancer

This is a single arm, open-label, prospective clinical trial to evaluate the combination of neoadjuvant short-course radiotherapy and toripalimab (PD-1 antibody) for locally advanced rectal cancer (LARC) patients with high risk factors. A total of 53patients 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 2 cycles of CAPOX chemotherapy. 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.

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer; MSS; Locally Advanced; High-Risk
• Intervention / Treatment: Drug: Toripalimab; Radiation: short-term radiotherapy; Drug: Oxaliplatin; Drug: Capecitabine

• Study Type: Interventional
• Enrollment (Estimated): 53
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yi Ding, MD; Phone Number: 86-20-13729852980; Email: dingyi197980@126.com
• Study Contact Backup: Name: Yaowei Zhang, MD; Phone Number: 86-20-17819575181; Email: weiyaozhang2@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Nanfang Hospital Southern Medical University
      • Contact: Yaowei Zhang, MD; Phone Number: 86-20-17819575181; Email: weiyaozhang2@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18-75 years old, female and male;
• Pathological confirmed MSS or pMMR rectal adenocarcinoma;
• Clinical stage T3-4 (AJCC 8th) and at least with one high risk factor（CRM+ or EMVI+ or lateral lymph nodes+）;
• No previous chemotherapy, radiotherapy, immunotherapy or other anti-tumor treatment;
• Adequate organ function defined at baseline as:

ANC ≥1.5××109/L，PLt ≥100×109 /L，Hb ≥90 g/L，15×109 /L≥WBC≥4×109 /L; TBIL ≤1.5×ULN, ALT ≤1.5ULN, AST ≤1.5ULN, BUN and Cr ≤1.5×ULN or Ccr

• 60ml/min (Cockcroft-Gault formula);INR ≤1.5×ULN or PT ≤1.5×ULN (when patient didn't accept anticoagulant therapy);

  • Women of childbearing age must have taken reliable contraceptive measures or have a pregnancy test (serum or urine) within 7 days prior to enrollment and the results are negative;

Exclusion Criteria:

• Pathological confirmed rectal squamous cell carcinoma;
• History of other uncured malignancies within 5 years;
• Allergic to any component of chemotherapy or immunotherapy;
• History of any active, known, or suspected autoimmune disease, including but not limited to myasthenia gravis,Myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,Inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener granulation Swollen disease, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis or Glomerulonephritis.
• With congenital or acquired immunodeficiency (such as those with HIV infection), active hepatitis B or hepatitis C;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: short-course radiotherapy plus chemotherapy and immunotherapy; A total of 53 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 2 cycles of CAPOX chemotherapy.	Drug: Toripalimab; Toripalimab 240mg,d1,q3w; Radiation: short-term radiotherapy; 25Gy/5Fx; Other Names: shor-course radiotherapy; Drug: Oxaliplatin; 135mg/m2 d1 q3w; Drug: Capecitabine; 1200mg/m2 d1-14 q3w

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR rate	Pathologic complete response rate	The TME surgery will be recommended after the neoadjuvant therapy. The pCR rate is evaluated after surgery. Assessed up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year OS	3-year overall survival rate	Assessed up to 3 years
3-year ORR	3-year objective response rate	Assessed up to 3 years
3-year DCR	3-year disease control rate	Assessed up to 3 years
AE	adverse event	Assessed up to 3 years
SAE	Serious Adverse Event	Assessed up to 3 years

Collaborators and Investigators

• Sponsor: Nanfang Hospital, Southern Medical University
• Collaborators: Shanghai Junshi Bioscience Co., Ltd.
• Investigators: Principal Investigator: Dehua Wu, MD, Nanfang Hospital, Southern Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2023
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: May 17, 2023
• First Submitted That Met QC Criteria: May 17, 2023
• First Posted (Actual): May 26, 2023

Study Record Updates

• Last Update Posted (Actual): July 5, 2023
• Last Update Submitted That Met QC Criteria: July 2, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine; Oxaliplatin
• Other Study ID Numbers: NFEC-2023-062

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No