Hypofractionated Radiotherapy Plus Immunotherapy Versus Conventional Radiotherapy in Locally Recurrent Rectal Cancer

Phase 2

Recruiting

• Conditions: Locally Recurrent Rectal Cancer
• Interventions: Radiation: Conventional Radiotherapy; Drug: Capecitabine; Drug: 5-fluorouracil; Drug: folinic acid; Drug: Oxaliplatin; Drug: Irinotecan; Drug: Cetuximab; Drug: Bevacizumab; Radiation: Hypofractionated radiotherapy; Drug: PD-1 antibody

• Registration Number: NCT06928584
• Lead Sponsor: Fudan University

Brief Summary

TORCH-R2 is a prospective, multicenter, randomized, phase II clinical trial. Patients aged 18 years or older with pelvic recurrence rectal cancer without synchronous distant metastases or recent chemo- and/or radiotherapy treatment, Eastern Cooperative Oncology Group performance status of 0-1will be enrolled . Patients will be randomized to receive either hypofractionated radiotherapy (25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation), 18 weeks sintilimab and investigator's choice of first-line chemotherapy +/- target therapy (experimental arm), or conventional radiotherapy (50Gy/25Fx irradiation or 39Gy/30Fx bid reirradiation) and chemotherapy +/- target therapy (control arm). Patiens will be restaged and followed by multidisciplinary team (MDT) for decision: radical surgery, sustained systerm+/- local treatment of non resection.

The primary endpoint was progression-free survival. Secondary endpoints were objective response rate (ORR), complete response rate, R0 resection rate, duration of response (DOR), overall survival (OS), and safety and tolerability of the treatment.

Detailed Description

Not available

Study Timeline

• Study Start: 2025-03-10
• Status Verified: 2025-04
• Study First Submitted: 2025-04-08
• Study First Submitted QC: 2025-04-14
• Last Update Submitted: 2025-04-14
• Study First Posted: 2025-04-15
• Last Update Posted: 2025-04-15
• Primary Completion: 2030-03-10
• Study Completion: 2030-03-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 221

Inclusion Criteria

Patient is 18-75 years. ECOG performance status 0-1. MRI/enhanced CT confirmed pelvic recurrence. Without synchronous distant metastases. No prior radiotherapy within 6 month. No prior first-line chemotherapy. Has an investigator determined life expectancy of at least 24 weeks. Demonstrate adequate organ function. Non pregnant or lactating patients. Fully informed and willing to provide written informed consent for the trial.

Exclusion Criteria

Neutrophil< 1.5×109/L, PLT< 100×109/L (PLT< 80×109/L in patients with livermetastasis), or Hb< 90 g/L.

TBIL > 1.5 ULN, or TBIL > 2.5 ULN in patients with liver metastasis. AST or ALT > 2.5 ULN, or ALT and/or AST > 5 ULN in patients with liver metastasis.

Cr > 1.5 ULN, or creatinine clearance< 50 mL/min (calculated according to Cockcroft Gault formula).

APTT > 1.5 ULN, PT > 1.5 ULN (subject to the normal value of the clinical trial research center).

Serious electrolyte abnormalities. Urinary protein ≥ 2+, or 24-h urine protein ≥1.0 g/24 h. Uncontrolled hypertension: SBP >140 mmHg or DBP > 90 mmHg. A history of arterial thrombosis or deep vein thrombosis within 6 months; a history of bleeding or evidence of bleeding tendency within 2 months.

A history of heart disease within 6 months. Uncontrolled malignant pleural effusion, ascites, or pericardial effusion. History of checkpoint inhibitor therapy. The presence of a clinically detectable second primary malignancy, or history of other malignancies within 5 years.

A history of liver disease including, but not limited to, HBV infection or HBV DNA positive (≥1×104/mL), HCV infection or HCV DNA positive (≥1×103/mL), and liver cirrhosis.

Pregnant or lactating women or women who may be pregnant have a positive pregnancy test before the first medication, or the female participants themselves and their partners who were unwilling to implement strict contraception during the study period.

The investigator considers that the subject is not suitable to participate in this clinical study due to any clinical or laboratory abnormalities or compliance problems.

Serious mental abnormalities. The diameter of brain metastasis is greater than 3 cm or the total volume is greater than 30 cc. Clinical or radiological evidence of spinal cord compression, or tumors within 3 mm of the spinal cord on MRI.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Conventional radiotherapy arm	Conventional Radiotherapy	Conventional radiotherapy (50Gy/25Fx irradiation or 39Gy/30Fx bid reirradiation) and investigator's choice of first-line chemotherapy +/- target therapy.
Conventional radiotherapy arm	Capecitabine	Conventional radiotherapy (50Gy/25Fx irradiation or 39Gy/30Fx bid reirradiation) and investigator's choice of first-line chemotherapy +/- target therapy.
Conventional radiotherapy arm	5-fluorouracil	Conventional radiotherapy (50Gy/25Fx irradiation or 39Gy/30Fx bid reirradiation) and investigator's choice of first-line chemotherapy +/- target therapy.
Conventional radiotherapy arm	Oxaliplatin	Conventional radiotherapy (50Gy/25Fx irradiation or 39Gy/30Fx bid reirradiation) and investigator's choice of first-line chemotherapy +/- target therapy.
Conventional radiotherapy arm	folinic acid	Conventional radiotherapy (50Gy/25Fx irradiation or 39Gy/30Fx bid reirradiation) and investigator's choice of first-line chemotherapy +/- target therapy.
Conventional radiotherapy arm	Bevacizumab	Conventional radiotherapy (50Gy/25Fx irradiation or 39Gy/30Fx bid reirradiation) and investigator's choice of first-line chemotherapy +/- target therapy.
Conventional radiotherapy arm	Irinotecan	Conventional radiotherapy (50Gy/25Fx irradiation or 39Gy/30Fx bid reirradiation) and investigator's choice of first-line chemotherapy +/- target therapy.
Conventional radiotherapy arm	Cetuximab	Conventional radiotherapy (50Gy/25Fx irradiation or 39Gy/30Fx bid reirradiation) and investigator's choice of first-line chemotherapy +/- target therapy.
Hypofractionated radiotherapy plus Immunotherapy arm	5-fluorouracil	Hypofractionated radiotherapy (25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation), 18 weeks sintilimab and investigator's choice of first-line chemotherapy +/- target therapy.
Hypofractionated radiotherapy plus Immunotherapy arm	Capecitabine	Hypofractionated radiotherapy (25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation), 18 weeks sintilimab and investigator's choice of first-line chemotherapy +/- target therapy.
Hypofractionated radiotherapy plus Immunotherapy arm	folinic acid	Hypofractionated radiotherapy (25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation), 18 weeks sintilimab and investigator's choice of first-line chemotherapy +/- target therapy.
Hypofractionated radiotherapy plus Immunotherapy arm	Oxaliplatin	Hypofractionated radiotherapy (25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation), 18 weeks sintilimab and investigator's choice of first-line chemotherapy +/- target therapy.
Hypofractionated radiotherapy plus Immunotherapy arm	Irinotecan	Hypofractionated radiotherapy (25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation), 18 weeks sintilimab and investigator's choice of first-line chemotherapy +/- target therapy.
Hypofractionated radiotherapy plus Immunotherapy arm	Cetuximab	Hypofractionated radiotherapy (25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation), 18 weeks sintilimab and investigator's choice of first-line chemotherapy +/- target therapy.
Hypofractionated radiotherapy plus Immunotherapy arm	Bevacizumab	Hypofractionated radiotherapy (25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation), 18 weeks sintilimab and investigator's choice of first-line chemotherapy +/- target therapy.
Hypofractionated radiotherapy plus Immunotherapy arm	Hypofractionated radiotherapy	Hypofractionated radiotherapy (25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation), 18 weeks sintilimab and investigator's choice of first-line chemotherapy +/- target therapy.
Hypofractionated radiotherapy plus Immunotherapy arm	PD-1 antibody	Hypofractionated radiotherapy (25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation), 18 weeks sintilimab and investigator's choice of first-line chemotherapy +/- target therapy.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival	up to 3 years	time from the date of start treatment until disease progression or censored at last follow-up or death.

Secondary Outcome Measures

Name	Time	Method
Objective response rate (ORR)	up to 1 year	the proportion of patients with the best response of confirmed complete or partial response according to RECIST 1.1, as assessed by the investigator.
Complete response rate	up to 1 year	the proportion of patients with the best response of confirmed complete response according to RECIST 1.1, as assessed by the investigator.
R0 resection rate	up to 1 year	the proportion of patients who achieve R0 resection of pelvic recurrent tumour after therapy.
Duration of response (DOR)	up to 3 years	time from the first documented pelvic objective response to pelvic or extrapelvic disease progression in patients with confirmed response.
Overall Survival	up to 3 years	from the date of start treatment until the date of death from any cause or censored at last follow-up.
Safety and tolerability	up to 1 year	proportion of patients with treatment-related acute toxicities as assessed by NCI CTCAE v5.0, from treatment initiation until 90 days upon completion of immunotherapy.

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China