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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
120

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 20, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 21, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 4, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 5, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 27, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 22, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

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