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.

NCT06823323 | Not Yet Recruiting

• 1 other identifier: 2024-0769
• Study Type: interventional
• Target: 150
• Locations: 0 countries
• Sites: N/A

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)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Objective Response Rate, ORR

  from enrollment to the end of treatment, up to 24 months.

Study Arms (2)

CapeOX + Pembrolizumab + Lactobacillus johnsonii Group

EXPERIMENTAL

Participants receive CapeOX + Pembrolizumab + Lactobacillus johnsonii

Dietary Supplement: Lactobacillus johnsonii

CapeOX + Pembrolizumab + Placebo Group

PLACEBO COMPARATOR

Participants receive CapeOX + Pembrolizumab + Placebo Group

Other: Placebo

Interventions

Lactobacillus johnsonii 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 + Lactobacillus johnsonii Group

Placebo OTHER

Placebo

CapeOX + Pembrolizumab + Placebo Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead
• First Affiliated Hospital of Wenzhou Medical University: collaborator
• Zhejiang Cancer Hospital: collaborator

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

CbsT2 protein, Lactobacillus johnsonii

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

Liangjing Wang

CONTACT

86-13777848083; wangljzju@zju.edu.cn

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: SPONSOR

Study Record Dates

• First Submitted: January 5, 2025
• First Posted: February 12, 2025
• Study Start: March 1, 2025
• Primary Completion: March 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 12, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share