Probiotics Enhance the Treatment of PD-1 Inhibitors in Patients With Liver Cancer

Study Overview
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Brief Summary
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Human microbes have been called the second genome of humanity.On May 13,2016,the White House launched the National Microbiome Initiative (NMI), with an estimated investment of us $521 million, to elevate microbiome research to a national strategic status. The gut is the largest microecological environment in the human body. The research in the field of intestinal microbiome has become one of the most advanced and hot research directions in the scientific field of the world today. At present, more than 50 diseases have been found to be related to intestinal microbiome disorders. Pd-1 (programmed death receptor 1) is an important immunosuppressive molecule.It regulates the immune system and promotes tolerance by down-regulating the immune system's response to human cells and by suppressing T cell inflammatory activity. In the past, the research team and colleagues in related fields have found a strong correlation between Gut Microbiome and the efficacy of anti-PD-1 immunotherapy in cancer patients.This protects against autoimmune diseases, but it also prevents the immune system from killing cancer cells. As more and more scientific evidence shows that intervention of human intestinal flora may improve the efficacy of anti-PD-1 immunotherapy in tumor patients, intestinal flora, as the most effective way to intervene human intestinal flora, has been mentioned by many research institutions and international drug manufacturers in combination with anti-PD-1.Our previous study showed that the abundance of beneficial bacteria such as lactic acid bacteria, bifidobacteria and Akkermansia Muciniphila was significantly correlated with pD-1 inhibitor response, and regulating the intestinal flora content could improve the effect of PD-1 inhibitor on mouse tumors, indicating that microbial flora was involved in regulating cancer immunotherapy.

Official Title
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Probiotics Enhance the Treatment of PD-1 Inhibitors in Patients With Liver Cancer

Conditions
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Liver Cancer

Intervention / Treatment
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* Other: M9
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Karnofsky score ≥90 in patients receiving immunotherapy for liver cancer at our cancer center Exclusion Criteria: any immune system disease under high risk to antimicrobial agents such as Diabetes,infection disease or drug allergy to V9

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: probiotics group<br>The oral probiotic (Lactobacillus rhamnosus Probio-M9,one times a day during the whole treatment) was isolated from healthy women's breast milk samples in 2017 and was identified as Lactobacillus rhamnosus by physiological and biochemical and 16S rRNA. It is listed as the List of Probiotics for Health Food in my country's List of Bacteria Available for Food, which can be directly applied to food production. | Other: M9<br>* one times a day during the whole treatment<br>|
| Placebo Comparator: placebo group<br>Immunotherapy with placebo alone | Other: placebo<br>* placebo<br>|
| No Intervention: healthy control group<br>healthy control group | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (objective remission rate)ORR | Proportion of patients whose tumor volume shrinks to a predetermined value and maintains the minimum time limit | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Time from randomness to the first occurrence of disease progression or death from any cause | 6 months | 
| OS | The time between random onset and the patient's death from any cause | 6 months |