Regorafenib Alone or in Combination With Hypofractionated/Low-dose Radiotherapy Plus Toripalimab for Metastatic Colorectal Cancer

Официальное название

A Prospective, Randomized, Controlled Phase II Trial of Regorafenib Alone or in Combination With Hypofractionated/Low-dose Radiotherapy Plus Toripalimab as Third-line Treatment in Patients With Metastatic Colorectal Cancer

Обзор

The study compares the efficacy and safety of regorafenib alone or in combination with hypofractionated radiotherapy and low-dose radiotherapy (LDRT) plus toripalimab in patients with microsatellite stable metastatic colorectal cancer (MSS mCRC). Patients are randomly assigned (1:1) into the control arm and the experimental arm. Control arm: a total of 54 patients will receive regorafenib monotherapy. Experimental arm: a total of 54 patients will first receive 1 cycle of regorafenib and toripalimab followed by hypofractionated/low-dose radiotherapy. Regorafenib and toripalimab will be continued after the completion of radiotherapy. The survival benefits, response rates, and adverse effects will be analyzed.

Подробное описание

Control arm: regorafenib 120 mg orally once daily on days 1-21 of each 28 days cycle.

Experimental arm: regorafenib is administered 80 mg once daily on days 1-21 of each 28 days cycle with intravenous toripalimab 240 mg every 3 weeks. Radiotherapy regimes include hypofractionated radiotherapy (5 fractions of 4-12Gy) and low-dose radiotherapy (5 fractions of 0.5-2Gy).

Вмешательства

• Препарат Regorafenib
  Regorafenib 120 mg orally once daily on days 1-21 of each 28 days cycle.
• Препарат Toripalimab
  240 mg intravenously every 3 weeks
• Лучевая терапия Radiotherapy
  hypofractionated radiotherapy (5 fractions of 4-12Gy) and low-dose radiotherapy (5 fractions of 0.5-2Gy).
• Препарат Regorafenib
  Regorafenib 80mg orally once daily on days 1-21 of each 28 days cycle.

Первичные конечные точки

• OS [Срок оценки: Up to 2 years]

Вторичные конечные точки (5)

• PFS [Срок оценки: Up to 2 years]
• DCR [Срок оценки: Up to 1 year]
• ORR [Срок оценки: Up to 1 year]
• DoR [Срок оценки: Up to 1 year]
• Adverse events [Срок оценки: Up to 1 year]

Критерии участия

Критерии включения

• Age ≥18 years old
• An Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• Life expectancy of at least 3 months
• Histopathological confirmed MSS/pMMR adenocarcinoma of the colon or rectum
• At least one evaluable metastatic lesion for radiotherapy according to RECIST 1.1
• Progressed on or after the standard first-and second-line therapies or stopped standard therapy because of unacceptable toxic effects
• Previous radiotherapy completed at least 4 weeks before randomization
• Adequate bone-marrow, hepatic, and renal function: neutrophils ≥ 1.5 × 10\^9/L, Hb ≥ 90 g/L, PLT ≥ 100 × 10\^9/L, ALT/ AST≤2.5 ULN, Cr≤1 ULN
• Sign the informed consent and have good compliance

Критерии исключения

• History of previous treatment with regorafenib and ICIs such as anti-PD-1 or anti-PD-L1 mAbs
• Current severe cardiovascular diseases such as unstable angina, congestive heart failure, or serious cardiac arrhythmia requiring medication
• Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before recruitment
• Active autoimmune diseases and immunodeficiencies, known history of organ transplantation, or systematic use of immunosuppressive agents
• Active Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection: HBsAg positive or HBV DNA positive, anti-HCV antibody testing positive and confirmatory HCV RNA positive
• Positive human immunodeficiency virus (HIV) infection, active syphilis infection, or active pulmonary tuberculosis infection
• Severe infections requiring systemic antibiotics, antifungal or antiviral therapy
• Uncontrollable pleural effusion, pericardial effusion, or ascites
• Other malignancies within 5 years before recruitment, except for non-melanoma skin cancer, superficial bladder cancer, cervical carcinoma in situ, or breast cancer in situ that had been effectively treated.
• Known history of severe neurological or mental illness such as schizophrenia, dementia, or epilepsy
• Known history of allergy to any component involved in this study.
• Pregnancy or breast-feeding women

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

Публикации

• Zhou S, Wang C, Shen L, Wang Y, Zhang H, Wu R, Wang Y, Chen Y, Xuan Y, Xia F, Zhang Z, Wan J. Regorafenib alone or in combination with high/low-dose radiotherapy plus toripalimab as third-line treatment in patients with metastatic colorectal cancer: protocol for a prospective, randomized, controlled phase II clinical trial (SLOT). Front Oncol. 2023 Oct 5;13:1274487. doi: 10.3389/fonc.2023.1274487. PMID 37869085

Идентификаторы

NCT: NCT05963490 · FDRT-2023-118-3237

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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