Short-course Radiotherapy Based TNT Combined With PD-1 Inhibitor for Locally Advanced Rectal Cancer

Locally Advanced Rectal Cancer Clinical Trial

— TORCH  

Official title:

A Prospective Phase II Trial of Short-course Radiotherapy Based Total Neoadjuvant Therapy Combined With PD-1 Inhibitor for Locally Advanced Rectal Cancer (TORCH）

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04518280
• Other study ID #: FDRT-2020-236-2156
• Status: Recruiting
• Phase: Phase 2
• Start date: May 1, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: September 2023
• Source: Fudan University
• Contact: Zhen Zhang, M.D, PH.D
• Phone: 18801735029
• Email: zhen_zhang[@]fudan.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

TORCH is a prospective, multicentre, randomized phase II trial. 130 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. Group A receives SCRT (25Gy/5Fx) followed by 6 cycles of Toripalimab combined with CAPOX (ToriCAPOX). Group B receives 2 cycles of ToriCAPOX followed by SCRT and 4 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, 3-year DFS rate, etc.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: December 31, 2025
• Est. primary completion date: October 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Pathological confrmed 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 immunodefciencies, known history of organ transplantation or systematic use of immunosuppressive agents

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

10. Active Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (i.e., HBsAg positive or HBV DNA positive, HCV RNA positive if anti-HCV antibody testing positive)

11. Allergic to any component of the therapy

Related Conditions & MeSH terms

• Locally Advanced Rectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• PD-1 antibody
PD-1 antibody (Toripalimab): 240mg d1 q3w
• Capecitabine
Capecitabine: 1000mg/m2 bid d1-14 q3w
• Oxaliplatin
Oxaliplatin: 130mg/m2 d1 q3w

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

Locations

Country	Name	City	State
China	Shanghai Changhai Hospital	Shanghai	Shanghai
China	Shanghai Changzheng Hospital	Shanghai	Shanghai
China	Shanghai East Hospital	Shanghai
China	Zhen Zhang	Shanghai	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.	The status of cCR will be evaluated after the completion of neoadjuvant therapy. The pCR rate will be evaluated after surgery. The cCR patients who adopted W&W strategy will be included into the CR rate caluculation.
Secondary	Grade 3-4 adverse effects rate	Rate of chemotherapy, radiotherapy and immunotherapy related adverse events	From date of randomization until the date of death from any cause, assessed up to 5 years
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 surgery was scheduled 2-4 weeks after the end of neoadjuvant therapy. And the surgical complications were assessed up to 5 years from the surgery.
Secondary	Scores of Quality of Life	Quality of life will be evaluated using EORTC QLQ-C30, EORTC QLQ-CR29, LARS score and Wexner score.	From date of randomization until the date of death from any cause, assessed up to 10 years