Short-course Radiotherapy Combined With CapeOx and PD-1 Inhibitor After Local Excision for High-risk Early Rectal Cancer (TORCH-LE)

Phase 2

Recruiting

• Conditions: Rectal Cancer
• Interventions: Radiation: Radiation; Drug: PD-1 antibody; Drug: Capecitabine; Drug: Oxaliplatin

• Registration Number: NCT06455124
• Lead Sponsor: Fudan University

Brief Summary

This is a single arm phase II study to explore the 3y LRFS and safety for high-risk early rectal cancer after local excision with short-course radiotherapy and chemo-immunotherapy.

Detailed Description

A total of 60 patients with high-risk pathologic stage pT1 or pT2 cancer after local excision but refused radical surgery will be included.

Eligibility criteria include a histological diagnosis of adenocarcinoma located ≤7 cm from the anal verge, pT1 after local excision of the primary rectal cancer, with one of the high-risk features including margin positivity/very close margin (\<1mm) at time of local excision, depth of invasion \>1 mm or SM3 invasion (submucosal invasion to the lower third of the submucosal level), high grade or poorly differentiated, lymphovascular invasion, perineural invasion, tumour budding, or pT2 tumor.

They will receive 5\*5Gy short-course radiotherapy, followed by 4 cycles of capecitabine plus oxaliplatin (CAPOX) chemotherapy and PD-1 antibody.

Study Timeline

• Study Start: 2024-05-08
• Status Verified: 2024-06
• Study First Submitted: 2024-06-06
• Study First Submitted QC: 2024-06-06
• Study First Posted: 2024-06-12
• Last Update Submitted: 2024-06-12
• Last Update Posted: 2024-06-13
• Primary Completion: 2026-06-30
• Study Completion: 2029-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. age 18-75 years old, female and male
2. pathological confirmed adenocarcinoma
3. the distance from anal verge ≤ 7 cm
4. pT1 after local excision of the primary rectal cancer, with at least one of the high-risk features including margin positivity/very close margin (<1mm) at time of local excision, depth of invasion >1 mm or SM3 invasion (submucosal invasion to the lower third of the submucosal level), high grade or poorly differentiated, lymphovascular invasion, perineural invasion, tumour budding, or pT2 tumor.
5. refuse radical surgery
6. without pelvic or distance metastases
7. KPS >=70
8. with good compliance
9. microsatellite repair status is MSS/pMMR
10. without previous anti-cancer therapy or immunotherapy
11. signed the inform consent

Exclusion Criteria

1. pregnancy or breast-feeding women
2. pathological confirmed signet ring cell carcinoma
3. history of other malignancies within 5 years
4. serious medical illness, such as severe mental disorders, cardiac disease, uncontrolled infection, etc.
5. immunodeficiency disease or long-term using of immunosuppressive agents
6. baseline blood and biochemical indicators do not meet the following criteria: neutrophils≥1.5×10^9/L, Hb≥90g/L, PLT≥100×10^9/L, ALT/AST ≤2.5 ULN, Cr≤ 1 ULN
7. DPD deficiency
8. allergic to any component of the therapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm1	Radiation	Patients will receive short course radiotherapy and four cycles of CapeOx and PD-1 inhibitor.
Arm1	PD-1 antibody	Patients will receive short course radiotherapy and four cycles of CapeOx and PD-1 inhibitor.
Arm1	Capecitabine	Patients will receive short course radiotherapy and four cycles of CapeOx and PD-1 inhibitor.
Arm1	Oxaliplatin	Patients will receive short course radiotherapy and four cycles of CapeOx and PD-1 inhibitor.

Primary Outcome Measures

Name	Time	Method
3y LRFS	From date of initiation of treatment until the date of first documented pelvic failure, assessed up to 36 months.	Rate of 3 year local recurrence free survival rate

Secondary Outcome Measures

Name	Time	Method
3y DFS	From date of initiation of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.	Rate of 3 year disease free survival
Grade 3-4 adverse effects rate	From date of initiation of treatment until the date of death from any cause, assessed up to 36 months.	Rate of chemotherapy, radiotherapy and immunotherapy related adverse events
3y OS	From date of initiation of treatment until the date of death from any cause, assessed up to 36 months.	Rate of 3 year overall survival

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, China