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)

Plain English Summary

CAPOX and PD-1 Antibody Combined With or Without Radiotherapy for MSS Locally Advanced Rectal Cancer is a Phase 2 clinical trial sponsored by Fudan University studying Locally Advanced Rectal Cancer, Neoadjuvant Therapy. This trial tests a combination of chemotherapy (CAPOX) and an immunotherapy drug (PD-1 antibody) to treat rectal cancer, with one group also receiving radiation therapy. It is for patients with locally advanced rectal cancer that has not spread to distant parts of the body and has specific characteristics (microsatellite stable). Participants will receive the study treatments before surgery, and may have the option to avoid surgery if their cancer responds well. Standard treatment for this condition often involves chemotherapy, radiation, and surgery, but this trial explores a different sequence and combination of therapies. The trial aims to enroll 192 participants.

Official 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, organ or anal preservation rate, 3-year DFS rate, etc.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients aged 18-70 with a confirmed diagnosis of rectal adenocarcinoma. The cancer must be locally advanced (T3-4 or N+) but not spread to distant organs, and located within 10 cm of the anus. Patients must have a specific tumor characteristic (MSS/pMMR) and meet certain health and blood count requirements. Individuals who have had prior cancer treatment, are pregnant, have other active cancers, or have certain autoimmune or severe medical conditions cannot participate. This trial is studying Locally Advanced Rectal Cancer, Neoadjuvant Therapy, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The main goal is to see if a higher percentage of patients achieve a complete response (either no detectable cancer after treatment or a clinical complete response) with the new treatment combination. The specific primary outcome measures are: Complete response (CR) rate (1 month after the surgery or the decision of W&W). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to improve treatment outcomes for locally advanced rectal cancer by investigating a novel combination of chemotherapy and immunotherapy, potentially reducing the need for radiation and Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Locally Advanced Rectal Cancer, Neoadjuvant Therapy, where improved treatment options are needed.

Investor Insight

This trial targets a significant unmet need in rectal cancer treatment, exploring a potentially more effective neoadjuvant approach that could lead to better patient outcomes and potentially reduce tr Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific chemotherapy drugs, immunotherapy, and radiation being used, and what the potential benefits and risks are for you. Understand the treatment schedule, which involves several cycles of therapy before potential surgery or a 'watch and wait' approach. Be prepared for regular clinic visits for treatment, monitoring, and potential side effect management. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 192 participants

Interventions

• DRUG: PD-1 inhibitor — PD-1 inhibitor (Toripalimab): 240mg d1 q3w
• DRUG: Capecitabine — Capecitabine: 1000mg/m2 bid d1-14 q3w
• RADIATION: Short-course radiotherapy — Short-course radiotherapy: 25Gy/5Fx
• DRUG: Oxaliplatin — Oxaliplatin 130mg/m2 d1 q3w

Primary Outcomes

• Complete response (CR) rate (1 month after the surgery or the decision of W&W)

Secondary Outcomes

• Grade 3-4 adverse effects rate (From date of randomization until 3 months after the completion neoadjuvant therapy)
• 3 year organ or anal preservation rate (From date of randomization until the resection of rectum or anus, assessed up to 36 months.)
• 3 year disease free survival rate (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.)
• 3 year local recurrence free survival rate (From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.)
• 3 year distant metastasis free survival rate (From date of randomization until the date of first documented distant metastasis, assessed up to 36 months.)

Full Eligibility Criteria

Inclusion Criteria

1. Age 18-70 years old, female and male;
2. Pathological confirmed adenocarcinoma;
3. The distance from anal verge ≤ 10 cm;
4. MSI/MMR status: MSS/pMMR;
5. Clinical stage T3-4 and/or N+, without distance metastases;
6. At least one of the following factors is present: distance from the anus ≤5 cm, cT4, cN2, positive cMRF, positive cEMVI, or positive lateral lymph nodes;
7. KPS ≥ 70;
8. No radiotherapy, chemotherapy, immunotherapy, or any other anti-tumor therapy had been administered prior to enrollment;
9. 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;
10. 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 severe neurological or mental illness (such as schizophrenia, dementia or epilepsy);
4. Current severe cardiac disease (cardiac dysfunction and arrhythmia), renal dysfunction and liver dysfunction;
5. Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before recruitment;
6. Uncontrolled infection which needs systemic therapy;
7. Active autoimmune disease or immunodeficiencies, known history of organ transplantation or systematic use of immunosuppressive agents;
8. Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1 to 2 antibody positive), active syphilis infection, active pulmonary tuberculosis infection;
9. Allergic to any component of the therapy.

Trial Locations

• Fudan University Shanghai Cancer Center, Shanghai, China

Frequently Asked Questions

Related Conditions

• Rectal Cancer
• Colorectal Cancer
• Gastrointestinal Cancers
• Oncology
• Neoadjuvant Therapy
• Immunotherapy
• Chemotherapy
• Radiation Therapy
• Microsatellite Stable Cancer
• Locally Advanced Cancer

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