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.

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

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.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer; Colorectal Cancer; Pancreatic Adenocarcinoma; Biliary Tract Cancer; Gastroesophageal Junction Adenocarcinoma; Liver Cancer Stage IV
• Intervention / Treatment: Radiation: Hypofractionated radiotherapy/SBRT（5-8 Gy/fx，3-5 fx）; Drug: Anti-PD-1 monoclonal antibody; Drug: Oxaliplatin and Capecitabine; Drug: Anti-VEGF 15mg/kg; Drug: Gemcitabine and Cisplatin; Drug: Gemcitabine and Albumin paclitaxel; Drug: Anti-VEGF 7.5mg/kg

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: zhu ji; Phone Number: 13501978674; Email: zhuji@zjcc.org.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Zhengjiang Cancer Hospital
      • Contact: Ji Zhu; Phone Number: 13501978674; Email: zhuji@zjcc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• histopathologically confirmed diagnosis of malignant tumors of the gastrointestinal tract (including Her-2 negative adenocarcinoma of the gastroesophageal junction/gastric adenocarcinoma, hepatocellular hepatocellular carcinoma, malignant tumors of the biliary system, pancreatic adenocarcinoma, colorectal adenocarcinoma);
• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARM A:Her-2 negative adenocarcinoma of the gastroesophageal junction/gastric adenocarcinoma; patients will receive Probio-M9 ,RT followed by Immunotherapy-Based Systemic Therapy	Radiation: Hypofractionated radiotherapy/SBRT（5-8 Gy/fx，3-5 fx）; RT: one primary or metastatic focus was selected for hypofractionated radiotherapy/SBRT (5-8 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.; Drug: Anti-PD-1 monoclonal antibody; Sintilimab 200mg d1 iv q3w; Drug: Oxaliplatin and Capecitabine; Oxaliplatin130mg/m2 d1 iv；Capecitabine1000mg/m2 d1-d14
Placebo Comparator: ARM A*:Her-2 negative adenocarcinoma of the gastroesophageal junction/gastric adenocarcinoma; patients will receive placebo ,RT followed by Immunotherapy-Based Systemic Therapy	Radiation: Hypofractionated radiotherapy/SBRT（5-8 Gy/fx，3-5 fx）; RT: one primary or metastatic focus was selected for hypofractionated radiotherapy/SBRT (5-8 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.; Drug: Anti-PD-1 monoclonal antibody; Sintilimab 200mg d1 iv q3w; Drug: Oxaliplatin and Capecitabine; Oxaliplatin130mg/m2 d1 iv；Capecitabine1000mg/m2 d1-d14
Experimental: ARM B: Liver adenocarcinoma; patients will receive Probio-M9 ,RT followed by Immunotherapy-Based Systemic Therapy	Radiation: Hypofractionated radiotherapy/SBRT（5-8 Gy/fx，3-5 fx）; RT: one primary or metastatic focus was selected for hypofractionated radiotherapy/SBRT (5-8 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.; Drug: Anti-PD-1 monoclonal antibody; Sintilimab 200mg d1 iv q3w; Drug: Anti-VEGF 15mg/kg; Bevacizumab 15mg/kg d1 iv q3w
Placebo Comparator: ARM B*: Liver adenocarcinoma; patients will receive placebo ,RT followed by Immunotherapy-Based Systemic Therapy	Radiation: Hypofractionated radiotherapy/SBRT（5-8 Gy/fx，3-5 fx）; RT: one primary or metastatic focus was selected for hypofractionated radiotherapy/SBRT (5-8 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.; Drug: Anti-PD-1 monoclonal antibody; Sintilimab 200mg d1 iv q3w; Drug: Anti-VEGF 15mg/kg; Bevacizumab 15mg/kg d1 iv q3w
Experimental: ARM C: Malignant tumors of the biliary system; patients will receive Probio-M9 ,RT followed by Immunotherapy-Based Systemic Therapy	Radiation: Hypofractionated radiotherapy/SBRT（5-8 Gy/fx，3-5 fx）; RT: one primary or metastatic focus was selected for hypofractionated radiotherapy/SBRT (5-8 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.; Drug: Anti-PD-1 monoclonal antibody; Sintilimab 200mg d1 iv q3w; Drug: Gemcitabine and Cisplatin; Gemcitabine1000mg/m2 d1 d8 iv；Cisplatin 25mg/m2 d1 d8 iv q3w
Placebo Comparator: ARM C*: Malignant tumors of the biliary system; patients will receive placebo ,RT followed by Immunotherapy-Based Systemic Therapy	Radiation: Hypofractionated radiotherapy/SBRT（5-8 Gy/fx，3-5 fx）; RT: one primary or metastatic focus was selected for hypofractionated radiotherapy/SBRT (5-8 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.; Drug: Anti-PD-1 monoclonal antibody; Sintilimab 200mg d1 iv q3w; Drug: Gemcitabine and Cisplatin; Gemcitabine1000mg/m2 d1 d8 iv；Cisplatin 25mg/m2 d1 d8 iv q3w
Experimental: ARM D：Pancreatic adenocarcinoma; patients will receive Probio-M9 ,RT followed by Immunotherapy-Based Systemic Therapy	Radiation: Hypofractionated radiotherapy/SBRT（5-8 Gy/fx，3-5 fx）; RT: one primary or metastatic focus was selected for hypofractionated radiotherapy/SBRT (5-8 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.; Drug: Anti-PD-1 monoclonal antibody; Sintilimab 200mg d1 iv q3w; Drug: Gemcitabine and Albumin paclitaxel; Gemcitabine1000mg/m2 d1 d8 iv；Albumin paclitaxel 125mg/m2 d1 d8 iv q3w
Placebo Comparator: ARM D*：Pancreatic adenocarcinoma; patients will receive placebo ,RT followed by Immunotherapy-Based Systemic Therapy	Radiation: Hypofractionated radiotherapy/SBRT（5-8 Gy/fx，3-5 fx）; RT: one primary or metastatic focus was selected for hypofractionated radiotherapy/SBRT (5-8 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.; Drug: Anti-PD-1 monoclonal antibody; Sintilimab 200mg d1 iv q3w; Drug: Gemcitabine and Albumin paclitaxel; Gemcitabine1000mg/m2 d1 d8 iv；Albumin paclitaxel 125mg/m2 d1 d8 iv q3w
Experimental: ARM E:Colorectal cancer; patients will receive Probio-M9 ,RT followed by Immunotherapy-Based Systemic Therapy	Radiation: Hypofractionated radiotherapy/SBRT（5-8 Gy/fx，3-5 fx）; RT: one primary or metastatic focus was selected for hypofractionated radiotherapy/SBRT (5-8 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.; Drug: Anti-PD-1 monoclonal antibody; Sintilimab 200mg d1 iv q3w; Drug: Oxaliplatin and Capecitabine; Oxaliplatin130mg/m2 d1 iv；Capecitabine1000mg/m2 d1-d14; Drug: Anti-VEGF 7.5mg/kg; Bevacizumab 7.5mg/kg d1 iv q3w
Placebo Comparator: ARM E*:Colorectal cancer; patients will receive placebo ,RT followed by Immunotherapy-Based Systemic Therapy	Radiation: Hypofractionated radiotherapy/SBRT（5-8 Gy/fx，3-5 fx）; RT: one primary or metastatic focus was selected for hypofractionated radiotherapy/SBRT (5-8 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.; Drug: Anti-PD-1 monoclonal antibody; Sintilimab 200mg d1 iv q3w; Drug: Oxaliplatin and Capecitabine; Oxaliplatin130mg/m2 d1 iv；Capecitabine1000mg/m2 d1-d14; Drug: Anti-VEGF 7.5mg/kg; Bevacizumab 7.5mg/kg d1 iv q3w

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	for off-target lesions of radiotherapy	ORR will be assessed 2 months after radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	irradiated lesion	ORR will be assessed 2 months after radiotherapy
adverse effects rate	CTC 4.0	From date of randomization until the date of death from any cause, assessed up to 5 years ]
Qol	EORTC-C30	From date of randomization until the date of death from any cause, assessed up to 10 years]
PFS	Rate of 3 year disease free survival	From the date of randomization to the date when progress was first recorded,assessed up to 36 months.
OS	Rate of 3 year overall survival	From date of randomization until the date of death from any cause, assessed up to 36 months
Qol	EQ-5D	From date of randomization until the date of death from any cause, assessed up to 10 years]

Collaborators and Investigators

• Sponsor: Zhejiang Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: March 21, 2024
• First Submitted That Met QC Criteria: April 4, 2024
• First Posted (Actual): April 5, 2024

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: immunotherapy; radiotherapy; metastatic; L. rhamnosus M9
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Biliary Tract Diseases; Adenocarcinoma; Biliary Tract Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Antibodies; Capecitabine; Oxaliplatin; Antibodies, Monoclonal; Gemcitabine
• Other Study ID Numbers: BASIMA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No