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.

NCT ID: NCT06823323

Last Updated: 2025-02-12

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-01
• Study Completion Date: 2026-06-01

Brief Summary

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.

Conditions

Metastatic Colorectal Cancer (CRC)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

CapeOX + Pembrolizumab + Lactobacillus johnsonii Group

Participants receive CapeOX + Pembrolizumab + Lactobacillus johnsonii

Group Type: EXPERIMENTAL

Lactobacillus johnsonii

Intervention Type: DIETARY_SUPPLEMENT

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.

CapeOX + Pembrolizumab + Placebo Group

Participants receive CapeOX + Pembrolizumab + Placebo Group

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo

Interventions

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.

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Placebo

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

First Affiliated Hospital of Wenzhou Medical University

OTHER

Sponsor Role: collaborator

Zhejiang Cancer Hospital

OTHER

Sponsor Role: collaborator

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Liangjing Wang

Role: CONTACT

wangljzju@zju.edu.cn

86-13777848083

Other Identifiers

2024-0769

Identifier Type: -

Identifier Source: org_study_id