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.

August 22, 2024 updated by: Ji Zhu, Zhejiang Cancer Hospital

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

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China
        • Recruiting
        • Zhengjiang Cancer Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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 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.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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
Drug: Anti-PD-1 monoclonal antibody
Sintilimab 200mg d1 iv q3w
Drug: Oxaliplatin and Capecitabine
Oxaliplatin130mg/m2 d1 iv；Capecitabine1000mg/m2 d1-d14
Radiation: 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.
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
Drug: Anti-PD-1 monoclonal antibody
Sintilimab 200mg d1 iv q3w
Drug: Oxaliplatin and Capecitabine
Oxaliplatin130mg/m2 d1 iv；Capecitabine1000mg/m2 d1-d14
Radiation: 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.
Experimental: ARM B: Liver adenocarcinoma
patients will receive Probio-M9 ,RT followed by Immunotherapy-Based Systemic Therapy
Drug: Anti-PD-1 monoclonal antibody
Sintilimab 200mg d1 iv q3w
Drug: Anti-VEGF 15mg/kg
Bevacizumab 15mg/kg d1 iv q3w
Radiation: 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.
Placebo Comparator: ARM B*: Liver adenocarcinoma
patients will receive placebo ,RT followed by Immunotherapy-Based Systemic Therapy
Drug: Anti-PD-1 monoclonal antibody
Sintilimab 200mg d1 iv q3w
Drug: Anti-VEGF 15mg/kg
Bevacizumab 15mg/kg d1 iv q3w
Radiation: 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.
Experimental: ARM C: Malignant tumors of the biliary system
patients will receive Probio-M9 ,RT followed by Immunotherapy-Based Systemic Therapy
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
Radiation: 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.
Placebo Comparator: ARM C*: Malignant tumors of the biliary system
patients will receive placebo ,RT followed by Immunotherapy-Based Systemic Therapy
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
Radiation: 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.
Experimental: ARM D:Colorectal cancer
patients will receive Probio-M9 ,RT followed by Immunotherapy-Based Systemic Therapy
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
Radiation: 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.
Placebo Comparator: ARM D*:Colorectal cancer
patients will receive placebo ,RT followed by Immunotherapy-Based Systemic Therapy
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
Radiation: 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Zhejiang Cancer Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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)

August 27, 2024

Last Update Submitted That Met QC Criteria

August 22, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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