A Randomized, Multicenter Phase II Basket Study of Hypofractionated Radiotherapy/Stereotactic Body Radiotherapy Followed by Immunotherapy-Based Systemic Therapy +/- L. Rhamnosus M9 for the First-Line Treatment of Advanced Digestive System Malignancies.

Официальное название

A Randomized, Multicenter Phase II Basket Study of Hypofractionated Radiotherapy/Stereotactic Body Radiotherapy Followed by Immunotherapy-Based Systemic Therapy +/- L. Rhamnosus M9 for the First-Line Treatment of Advanced Digestive System Malignancies

Обзор

Based on the interaction between radiation therapy and immunotherapy and the potential potentiation of Probio-M9 for the treatment of ICIs, this study is planned to design an integrated treatment protocol for the first-line treatment of advanced gastrointestinal tumors through the use of macrofractionated radiotherapy as a means of immune activation, combined with the synergistic effect of Probio-M9 microbial agents and PD-1 inhibitors.

Вмешательства

• Лучевая терапия Hypofractionated radiotherapy/SBRT（5-10Gy/fx，3-5 fx）
  RT: one primary or metastatic focus was selected for hypofractionated radiotherapy/SBRT (5-10 Gy/fx, 3-5 fx) in each round, the target area included only the GTV of the visible tumor lesion, and the GTV was expanded by 5-10 mm to generate the PTV, and the prophylactic lymphatic drainage area could not be irradiated.
• Препарат Anti-PD-1 monoclonal antibody
  Sintilimab 200mg d1 iv q3w
• Препарат Oxaliplatin and Capecitabine
  Oxaliplatin130mg/m2 d1 iv；Capecitabine1000mg/m2 d1-d14
• Препарат Anti-VEGF 15mg/kg
  Bevacizumab 15mg/kg d1 iv q3w
• Препарат Anti-VEGF 7.5mg/kg
  Bevacizumab 7.5mg/kg d1 iv q3w
• Препарат Gemcitabine and Cisplatin
  Gemcitabine1000mg/m2 d1 d8 iv；Cisplatin 25mg/m2 d1 d8 iv q3w

Первичные конечные точки

• ORR [Срок оценки: ORR will be assessed 2 months after radiotherapy]

Вторичные конечные точки (6)

• ORR [Срок оценки: ORR will be assessed 2 months after radiotherapy]
• adverse effects rate [Срок оценки: From date of randomization until the date of death from any cause, assessed up to 5 years ]]
• Qol [Срок оценки: From date of randomization until the date of death from any cause, assessed up to 10 years]]
• PFS [Срок оценки: From the date of randomization to the date when progress was first recorded,assessed up to 36 months.]
• OS [Срок оценки: From date of randomization until the date of death from any cause, assessed up to 36 months]
• Qol [Срок оценки: From date of randomization until the date of death from any cause, assessed up to 10 years]]

Критерии участия

Критерии включения

• histopathologically confirmed diagnosis of malignant tumors of the gastrointestinal tract (including Her-2 negative adenocarcinoma of the gastroesophageal junction/gastric adenocarcinoma, hepatocellular carcinoma, malignant tumors of the biliary system, colorectal cancer);
• advanced patients evaluated as initially non-operable resectable who have not received any antitumor therapy;
• have at least one measurable or evaluable lesion according to RECIST v1.1 criteria in addition to the primary lesion, with non-operable resectable lymph node metastases to the liver, lung, bone, pelvis, retroperitoneum and/or superficial sites (except for brain metastases), as evaluated by discussion in the framework of the MDT
• age 18-75 years;
• ECOG score of 0-1;
• be able to accept the treatment regimen during the study;
• sign a written informed consent.

Критерии исключения

• a history of uncontrolled epilepsy, central nervous system disease, or psychiatric disorder of clinical severity that, in the judgment of the investigator, may preclude the signing of an informed consent form or interfere with the patient's adherence to oral medication;
• prior immunotherapy for any indication or a history of severe hypersensitivity reactions to other monoclonal antibodies;
• clinically significant (i.e., active) cardiac disease, such as symptomatic coronary artery disease, New York Heart Association (NYHA) class II or worse congestive heart failure or severe arrhythmias requiring pharmacologic intervention, or history of myocardial infarction within the last 12 months;
• organ transplantation requiring immunosuppressive therapy;
• a history of other malignant disease within the last five years;
• persons with severe uncontrolled recurrent infections, or other severe uncontrolled concomitant diseases;
• Subjects whose baseline blood routine and biochemical indexes do not meet the following criteria: hemoglobin ≥80g/L; absolute neutrophil count (ANC) ≥1.5×10\^9/L; platelets ≥100×10\^9/L; ALT, AST ≤2.5 times the upper limit of normal; ALP ≤2.5 times the upper limit of normal; serum total bilirubin <1.5 times the upper limit of normal; serum creatinine <1 times the upper limit of normal; and serum creatinine <1 times the upper limit of normal. times the upper limit of normal;
• the patient currently has active gastrointestinal diseases such as active gastric and duodenal ulcers, ulcerative colitis, or active bleeding from unresected tumors, or other conditions that may cause gastrointestinal bleeding or perforation as determined by the investigator;
• persons with active bleeding or bleeding tendencies;
• women who are pregnant or breastfeeding;
• allergy to any of the study drug ingredients.

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

Двойное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Zhengjiang Cancer Hospital — Ханчжоу

Идентификаторы

NCT: NCT06349044 · BASIMA

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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