Clinical trial NCT06928584: Hypofractionated Radiotherapy Plus Immunotherapy Versus Conventional Radiotherapy in Locally Recurrent Rectal Cancer
Official title: Multicenter, Randomized, Phase II Trial of Neoadjuvant Hypofractionated Radiotherapy Plus Immunotherapy and First-line Therapy Versus Conventional Radiotherapy Plus First-line Therapy in pMMR Locally Recurrent Rectal Cancer (TORCH-R2)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Locally Recurrent Rectal Cancer
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2025-04-15
Enrollment: 221
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression-Free Survival
timeFrame: up to 3 years
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: up to 1 year
measure: Complete response rate
timeFrame: up to 1 year
measure: R0 resection rate
timeFrame: up to 1 year
measure: Duration of response (DOR)
timeFrame: up to 3 years
measure: Overall Survival
timeFrame: up to 3 years
measure: Safety and tolerability
timeFrame: up to 1 year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Zhen Zhang, MD PhD, PhD
role: PRINCIPAL_INVESTIGATOR
References: