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.
1 other identifier
interventional
120
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable
Started Mar 2024
Typical duration for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 20, 2024
CompletedFirst Submitted
Initial submission to the registry
March 21, 2024
CompletedFirst Posted
Study publicly available on registry
April 5, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2025
CompletedAugust 27, 2024
August 1, 2024
1.8 years
March 21, 2024
August 22, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
ORR
for off-target lesions of radiotherapy
ORR will be assessed 2 months after radiotherapy
Secondary Outcomes (6)
ORR
ORR will be assessed 2 months after radiotherapy
adverse effects rate
From date of randomization until the date of death from any cause, assessed up to 5 years ]
Qol
From date of randomization until the date of death from any cause, assessed up to 10 years]
PFS
From the date of randomization to the date when progress was first recorded,assessed up to 36 months.
OS
From date of randomization until the date of death from any cause, assessed up to 36 months
- +1 more secondary outcomes
Study Arms (8)
ARM A:Her-2 negative adenocarcinoma of the gastroesophageal junction/gastric adenocarcinoma
EXPERIMENTALpatients will receive Probio-M9 ,RT followed by Immunotherapy-Based Systemic Therapy
ARM A*:Her-2 negative adenocarcinoma of the gastroesophageal junction/gastric adenocarcinoma
PLACEBO COMPARATORpatients will receive placebo ,RT followed by Immunotherapy-Based Systemic Therapy
ARM B: Liver adenocarcinoma
EXPERIMENTALpatients will receive Probio-M9 ,RT followed by Immunotherapy-Based Systemic Therapy
ARM B*: Liver adenocarcinoma
PLACEBO COMPARATORpatients will receive placebo ,RT followed by Immunotherapy-Based Systemic Therapy
ARM C: Malignant tumors of the biliary system
EXPERIMENTALpatients will receive Probio-M9 ,RT followed by Immunotherapy-Based Systemic Therapy
ARM C*: Malignant tumors of the biliary system
PLACEBO COMPARATORpatients will receive placebo ,RT followed by Immunotherapy-Based Systemic Therapy
ARM D:Colorectal cancer
EXPERIMENTALpatients will receive Probio-M9 ,RT followed by Immunotherapy-Based Systemic Therapy
ARM D*:Colorectal cancer
PLACEBO COMPARATORpatients will receive placebo ,RT followed by Immunotherapy-Based Systemic Therapy
Interventions
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.
Sintilimab 200mg d1 iv q3w
Oxaliplatin130mg/m2 d1 iv；Capecitabine1000mg/m2 d1-d14
Bevacizumab 15mg/kg d1 iv q3w
Gemcitabine1000mg/m2 d1 d8 iv；Cisplatin 25mg/m2 d1 d8 iv q3w
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Zhengjiang Cancer Hospital
Hangzhou, Zhejiang, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, CARE PROVIDER
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
March 21, 2024
First Posted
April 5, 2024
Study Start
March 20, 2024
Primary Completion
December 31, 2025
Study Completion
December 31, 2025
Last Updated
August 27, 2024
Record last verified: 2024-08