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

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

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

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

Number of Arms

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

Studies a U.S. FDA-regulated device product

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.

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.