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

NCT06928584 | Recruiting Phase 2

• 1 other identifier: FDRT-2024-416-3970
• Study Type: interventional
• Target: 221
• Locations: 1 country
• Sites: 1

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.

Conditions

Locally Recurrent Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival

  time from the date of start treatment until disease progression or censored at last follow-up or death.

  up to 3 years

Secondary Outcomes (6)

• Objective response rate (ORR)

  up to 1 year

• Complete response rate

  up to 1 year

• R0 resection rate

  up to 1 year

• Duration of response (DOR)

  up to 3 years

• Overall Survival

  up to 3 years

Study Arms (2)

Conventional radiotherapy arm

ACTIVE COMPARATOR

Conventional radiotherapy (50Gy/25Fx irradiation or 39Gy/30Fx bid reirradiation) and investigator's choice of first-line chemotherapy +/- target therapy.

Radiation: Conventional Radiotherapy; Drug: Capecitabine; Drug: 5-fluorouracil; Drug: folinic acid; Drug: Oxaliplatin; Drug: Irinotecan; Drug: Cetuximab; Drug: Bevacizumab

Hypofractionated radiotherapy plus Immunotherapy arm

EXPERIMENTAL

Hypofractionated radiotherapy (25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation), 18 weeks sintilimab and investigator's choice of first-line chemotherapy +/- target therapy.

Drug: Capecitabine; Drug: 5-fluorouracil; Drug: folinic acid; Drug: Oxaliplatin; Drug: Irinotecan; Drug: Cetuximab; Drug: Bevacizumab; Radiation: Hypofractionated radiotherapy; Drug: PD-1 antibody

Interventions

Conventional Radiotherapy RADIATION

50Gy/25Fx irradiation or 39Gy/30Fx bid reirradiation (previous pelvic radiation)

Conventional radiotherapy arm

Capecitabine DRUG

1000mg/m2 d1-14 q3w

Conventional radiotherapy arm; Hypofractionated radiotherapy plus Immunotherapy arm

5-fluorouracil DRUG

400 mg/m2 (bolus) and 2400 mg/m2 (continuous infusion for 48hr)

Conventional radiotherapy arm; Hypofractionated radiotherapy plus Immunotherapy arm

folinic acid DRUG

400 mg/m2 q2w

Conventional radiotherapy arm; Hypofractionated radiotherapy plus Immunotherapy arm

Oxaliplatin DRUG

130 mg/m² q3w or 85 mg/m² q2w

Conventional radiotherapy arm; Hypofractionated radiotherapy plus Immunotherapy arm

Irinotecan DRUG

180 mg/m² q2w and 200 mg/m² q3w

Conventional radiotherapy arm; Hypofractionated radiotherapy plus Immunotherapy arm

Cetuximab DRUG

500 mg/m² q2w

Conventional radiotherapy arm; Hypofractionated radiotherapy plus Immunotherapy arm

Bevacizumab DRUG

5 mg/kg q2w or 7.5mg/kg q3w

Conventional radiotherapy arm; Hypofractionated radiotherapy plus Immunotherapy arm

Hypofractionated radiotherapy RADIATION

25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation (previous pelvic radiation)

Hypofractionated radiotherapy plus Immunotherapy arm

PD-1 antibody DRUG

200mg IV q3w

Also known as: Sintilimab

Hypofractionated radiotherapy plus Immunotherapy arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Interventions

Capecitabine; Fluorouracil; Leucovorin; Oxaliplatin; Irinotecan; Cetuximab; Bevacizumab; Radiation Dose Hypofractionation; spartalizumab; sintilimab

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics

Study Officials

• Zhen Zhang, MD PhD, PhD

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhen Zhang, MD, PhD

CONTACT

86-18801735029; zhen_zhang@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 8, 2025
• First Posted: April 15, 2025
• Study Start: March 10, 2025
• Primary Completion (Estimated): March 10, 2030
• Study Completion (Estimated): March 10, 2030
• Last Updated: April 15, 2025

Record last verified: 2025-04

Locations

CN (1)