The Study on the Efficacy and Safety of Lactobacillus Johnsonii in Combination with CapeOX and Pembrolizumab for the Treatment of MSS/pMMR Metastatic Colorectal Cancer. (MSSpMMRCapeOX)

The Study on the Efficacy and Safety of Lactobacillus Johnsonii in Combination with CapeOX and Pembrolizumab for the Treatment of MSS/pMMR Metastatic Colorectal Cancer- a Prospective, Multicenter, Double-blind, Randomized Controlled Study.

The goal of this clinical trial is to verify the effectiveness and safety of Lactobacillus johnsonii in combination with CapeOX and Pembrolizumab for the treatment of MSS/pMMR metastatic colorectal cancer (CRC). The main questions it aims to answer are:

① To verify the effectiveness of Lactobacillus johnsonii in the treatment of MSS/pMMR type metastatic colorectal cancer (mCRC) who have failed the standard regimen of chemotherapy;

② To explore the safety of Lactobacillus johnsonii in the treatment of MSS/pMMR type metastatic colorectal cancer (mCRC) who have failed the standard regimen of chemotherapy.

Participants who meet all the inclusion criteria will be enrolled in the study and randomly assigned in a 1:1 ratio to either the CapeOX + Pembrolizumab + placebo group or the CapeOX + Pembrolizumab + Lactobacillus johnsonii group.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Colorectal Cancer (CRC)
• Intervention / Treatment: Other: Placebo; Dietary supplement: Lactobacillus johnsonii

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Liangjing Wang; Phone Number: 86-13777848083; Email: wangljzju@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Ages between 18 and 75 years old;

  • Pathologically confirmed MSS or pMMR colorectal adenocarcinoma (PCR method, with 0 or 1 locus unstable; or immunohistochemical method, with expression of MLH1/MSH2/MSH6/PMS2 proteins);

    • Patients who have failed standard first- and second-line treatments (including CapeOX ± targeted therapy, FOLFOX ± targeted therapy, 5-FU/LV ± targeted therapy); ④ Radiological imaging indicates distant metastases throughout the body, considered as unresectable lesions; ⑤ Willingness to comply with the study visit schedule, as well as the prohibitions and restrictions stipulated in this agreement.

Exclusion Criteria

• Use of antibiotics within 4 weeks prior to treatment;

  • Concurrent immunodeficiency diseases (such as HIV or post-transplantation status) or receipt of high-dose systemic corticosteroid therapy or any other form of immunosuppressive therapy within the last 4 weeks;

    • Concurrent malignancies in other organs; ④ Concurrent active autoimmune diseases (i.e., requiring corticosteroids or immunosuppressant medications);

      • Concurrent active infections requiring systemic treatment; ⑥ Concurrent severe systemic diseases, diseases of vital organs such as the heart, lungs, and brain, liver and renal insufficiency, among others;

        • Participation in other drug studies within 3 months prior to treatment or inability of the patient to correctly express their chief complaints and cooperate with this study; ⑧ Any severe or uncontrolled medical condition that, in the investigator's opinion, may increase the risks associated with study participation or study drug administration, impair the subject's ability to receive the protocol-specified treatment, or interfere with the interpretation of study results.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CapeOX + Pembrolizumab + Lactobacillus johnsonii Group; Participants receive CapeOX + Pembrolizumab + Lactobacillus johnsonii	Dietary supplement: Lactobacillus johnsonii; It is previously reported Lactobacillus johnsonii #CGMCC29884 in Cell. Animal studies showed it combined with Clostridium sporogenes to produce indolepropionic acid, modulating CD8+ T cell immune quiescence in the tumor microenvironment and sensitizing immunotherapy in CRC, breast cancer, and melanoma. Mager et al. found Lactobacillus johnsonii enhanced CTLA-4 mAb antitumor effects in CRC mouse models. Studies showed it's a typical probiotic widely distributed in various hosts' guts and has long been applied in food and feed industries. Preclinical studies indicated it improved memory through the gut-brain axis, had anti-inflammatory and antibacterial effects, and regulated metabolic diseases. Randomized trials found it effectively inhibited Helicobacter pylori colonization without obvious adverse reactions, suggesting it's a potentially safe and effective treatment.
Placebo Comparator: CapeOX + Pembrolizumab + Placebo Group; Participants receive CapeOX + Pembrolizumab + Placebo Group	Other: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	Progression-Free Survival (PFS), as per RECIST 1.1 criteria, assessed by blinded independent review, is defined as the time from randomization to the occurrence of tumor progression or death from any cause, whichever comes first, up to 24 months.	from randomization to the occurrence of tumor progression or death from any cause, whichever comes first, up to 24 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate, ORR	Objective Response Rate (ORR) is defined as the proportion of patients who achieve either a Complete Response (CR) or a Partial Response (PR), as determined by blinded independent review according to RECIST 1.1 criteria.	from enrollment to the end of treatment, up to 24 months.

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: Zhejiang Cancer Hospital; First Affiliated Hospital of Wenzhou Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: January 5, 2025
• First Submitted That Met QC Criteria: February 9, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 9, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 2024-0769

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No