CAPOX and PD-1 Antibody Combined With or Without Radiotherapy for MSS Locally Advanced Rectal Cancer

Neoadjuvant Therapy Clinical Trial

— TORCH-iTNT  

Official title:

A Prospective Randomized Phase II Trial of CAPOX and PD-1 Antibody Combined With or Without Radiotherapy for Microsatellite Stable Locally Advanced Rectal Cancer (TORCH-iTNT)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06281405
• Other study ID #: FDRT-2023-290-3409
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: March 1, 2024
• Est. completion date: December 31, 2028

Study information

• Verified date: February 2024
• Source: Fudan University
• Contact: Zhen Zhang, MD
• Phone: 18801735029
• Email: zhen_zhang[@]fudan.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

TORCH-iTNT is a prospective, multicentre, randomized phase II trial. 198 LARC (T3-4/N+M0, distance from anal verge ≤12cm) patients will be treated with total neoadjuvant therapy (TNT) and assigned to Group A and Group B (1:1). Group A receives 6 cycles of Toripalimab combined with CAPOX (ToriCAPOX). Group B receives SCRT (25Gy/5Fx) followed by 6 cycles of ToriCAPOX. TME surgery is scheduled after TNT while a watch and wait (W&W) option can be applied to patients achieving clinical complete response (cCR). The primary endpoint is complete response (CR, pathological complete response [pCR] plus cCR) rate. The secondary endpoints include the grade 3-4 acute adverse effects (AE) rate, anal preservation rate, 3-year DFS rate, etc.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 198
• Est. completion date: December 31, 2028
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Pathological confirmed adenocarcinoma;

2. Clinical stage T3-4 and/or N+;

3. The distance from anal verge = 12 cm;

4. Without distance metastases;

5. Age 18-70 years old, female and male;

6. KPS = 70;

7. Baseline blood and biochemical indicators meet the following criteria: neutrophils = 1.5 × 10^9/L, Hb = 90 g/L, PLT = 100 × 10^9/L, ALT/ AST = 2.5 ULN, Cr = 1 ULN;

8. With good compliance and signed the consent form.

Exclusion Criteria:

1. Pregnancy or breast-feeding women;

2. Known history of other malignancies within 5 years;

3. Known history of previous anti-tumor treatment, including radiotherapy, chemotherapy, immune checkpoint inhibitors, T cell-related therapy, etc;

4. Known history of severe neurological or mental illness (such as schizophrenia, dementia or epilepsy);

5. Current severe cardiac disease (cardiac dysfunction and arrhythmia), renal dysfunction and liver dysfunction;

6. Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before recruitment;

7. Uncontrolled infection which needs systemic therapy;

8. Active autoimmune disease or immunodeficiencies, known history of organ transplantation or systematic use of immunosuppressive agents;

9. Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1 to 2 antibody positive), active syphilis infection, active pulmonary tuberculosis infection

10. Allergic to any component of the therapy.

Related Conditions & MeSH terms

• Locally Advanced Rectal Cancer
• Neoadjuvant Therapy
• Rectal Neoplasms

Intervention

Drug:
• PD-1 antibody
PD-1 antibody (Toripalimab): 240mg d1 q3w
• Capecitabine
Capecitabine: 1000mg/m2 bid d1-14 q3w

Radiation:
• Short-course radiotherapy
Short-course radiotherapy: 25Gy/5Fx

Locations

Country	Name	City	State
China	Fudan University Shanghai Cancer Center	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete response (CR) rate	Rate of complete response (CR), including the rate of pathologic complete response (pCR) after surgery and the rate of cCR with W&W strategy.	1 month after the surgery or the decision of W&W
Secondary	Grade 3-4 adverse effects rate	Rate of chemotherapy, radiotherapy and immunotherapy related adverse events	From date of randomization until 3 months after the completion neoadjuvant therapy
Secondary	3 year anal preservation rate	3 year anal preservation rate	From date of randomization until the date of or date of death from any cause, whichever came first, assessed up to 36 months.
Secondary	3 year disease free survival rate	Rate of 3 year disease free survival	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
Secondary	3 year local recurrence free survival rate	Rate of 3 year local recurrence free survival	From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.
Secondary	3 year overall survival rate	Rate of 3 year overall survival	From date of randomization until the date of death from any cause, assessed up to 36 months.
Secondary	Rate of surgical complications	Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.	The surgical complications were assessed within 3 months after the surgery.