Clinical trial NCT06281405: CAPOX and PD-1 Antibody Combined With or Without Radiotherapy for MSS Locally Advanced Rectal Cancer
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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Locally Advanced Rectal Cancer
Neoadjuvant Therapy
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2024-02-28
Enrollment: 198
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Complete response (CR) rate
timeFrame: 1 month after the surgery or the decision of W&W
Secondary outcomes:
measure: Grade 3-4 adverse effects rate
timeFrame: From date of randomization until 3 months after the completion neoadjuvant therapy
measure: 3 year anal preservation rate
timeFrame: From date of randomization until the date of or date of death from any cause, whichever came first, assessed up to 36 months.
measure: 3 year disease free survival rate
timeFrame: 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.
measure: 3 year local recurrence free survival rate
timeFrame: From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.
measure: 3 year overall survival rate
timeFrame: From date of randomization until the date of death from any cause, assessed up to 36 months.
measure: Rate of surgical complications
timeFrame: The surgical complications were assessed within 3 months after the surgery.
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
Study officials:
affiliation: Fudan University
name: Zhen Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References: