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

Официальное название

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)

Обзор

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.

Вмешательства

• Лучевая терапия Conventional Radiotherapy
  50Gy/25Fx irradiation or 39Gy/30Fx bid reirradiation (previous pelvic radiation)
• Препарат Capecitabine
  1000mg/m2 d1-14 q3w
• Препарат 5-fluorouracil
  400 mg/m2 (bolus) and 2400 mg/m2 (continuous infusion for 48hr)
• Препарат folinic acid
  400 mg/m2 q2w
• Препарат Oxaliplatin
  130 mg/m² q3w or 85 mg/m² q2w
• Препарат Irinotecan
  180 mg/m² q2w and 200 mg/m² q3w
• Препарат Cetuximab
  500 mg/m² q2w
• Препарат Bevacizumab
  5 mg/kg q2w or 7.5mg/kg q3w
• Лучевая терапия Hypofractionated radiotherapy
  25-40Gy/5Fx irradiation or 15-30Gy/5Fx reirradiation (previous pelvic radiation)
• Препарат PD-1 antibody
  200mg IV q3w

Первичные конечные точки

• Progression-Free Survival [Срок оценки: up to 3 years]

Вторичные конечные точки (6)

• Objective response rate (ORR) [Срок оценки: up to 1 year]
• Complete response rate [Срок оценки: up to 1 year]
• R0 resection rate [Срок оценки: up to 1 year]
• Duration of response (DOR) [Срок оценки: up to 3 years]
• Overall Survival [Срок оценки: up to 3 years]
• Safety and tolerability [Срок оценки: up to 1 year]

Критерии участия

Критерии включения

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.

Критерии исключения

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Fudan University Shanghai Cancer Center — Шанхай

Идентификаторы

NCT: NCT06928584 · FDRT-2024-416-3970

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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