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.

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06349044
• Other study ID #: BASIMA
• Status: Recruiting
• Phase: N/A
• Start date: March 20, 2024
• Est. completion date: December 31, 2025

Study information

• Verified date: April 2024
• Source: Zhejiang Cancer Hospital
• Contact: zhu ji
• Phone: 13501978674
• Email: zhuji[@]zjcc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Biliary Tract Cancer
• Biliary Tract Neoplasms
• Colorectal Cancer
• Gastric Cancer
• Gastroesophageal Junction Adenocarcinoma
• Liver Cancer Stage IV
• Pancreatic Adenocarcinoma

Intervention

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
• Oxaliplatin and Capecitabine
Oxaliplatin130mg/m2 d1 iv;Capecitabine1000mg/m2 d1-d14
• Anti-VEGF 15mg/kg
Bevacizumab 15mg/kg d1 iv q3w
• Anti-VEGF 7.5mg/kg
Bevacizumab 7.5mg/kg d1 iv q3w
• Gemcitabine and Cisplatin
Gemcitabine1000mg/m2 d1 d8 iv;Cisplatin 25mg/m2 d1 d8 iv q3w
• Gemcitabine and Albumin paclitaxel
Gemcitabine1000mg/m2 d1 d8 iv;Albumin paclitaxel 125mg/m2 d1 d8 iv q3w

Locations

Country	Name	City	State
China	Zhengjiang Cancer Hospital	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Zhejiang Cancer Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ORR	for off-target lesions of radiotherapy	ORR will be assessed 2 months after radiotherapy
Secondary	ORR	irradiated lesion	ORR will be assessed 2 months after radiotherapy
Secondary	adverse effects rate	CTC 4.0	From date of randomization until the date of death from any cause, assessed up to 5 years ]
Secondary	Qol	EORTC-C30	From date of randomization until the date of death from any cause, assessed up to 10 years]
Secondary	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.
Secondary	OS	Rate of 3 year overall survival	From date of randomization until the date of death from any cause, assessed up to 36 months
Secondary	Qol	EQ-5D	From date of randomization until the date of death from any cause, assessed up to 10 years]