RecruitingPhase 2NCT05502913

Fecal Microbiota Transplantation With Immune Checkpoint Inhibitors in Lung Cancer

Fecal Microbiota Transplantation to Improve Efficacy of Immune Checkpoint Inhibitors in Metastatic Lung Cancer

Sponsor

Soroka University Medical Center

Enrollment

80 participants

Start Date

Sep 1, 2023

Study Type

INTERVENTIONAL

Conditions

Metastatic Lung Cancer

Summary

Immunotherapy has recently become a main-stream treatment option in cancer care, with improved clinical outcomes in many malignancies, especially that of lung cancer. The long-term benefits of this treatment however are limited. There is therefore a critical need to distinguish predictive biomarkers of response from those of resistance, and to develop synergistic strategies for improved therapeutic response. Strong emerging evidence indicates that the gut microbiome has the ability to influence response to immunotherapy. Unlike tumor genomics, the gut microbiome is modifiable, and thus its modulation to enhance response to immunotherapy is an attractive therapeutic strategy. Working hypothesis: Fecal Microbiota Transplant (FMT) treatment in conjunction with standard (chemo-)immunotherapy as a first-line treatment for metastatic lung cancer enhances disease control rate. The main objective of this study is to evaluate the safety and efficacy of Fecal Microbiota Transplant (FMT) in altering response to immunotherapy in patients with metastatic lung cancer. The overall goal is to determine microbiome compositional and gene-content changes in patients who respond more efficiently to immunotherapy subsequent to FMT. This understanding may lead to future microbiome-based treatments in combination with immunotherapy to significantly increase lung cancer treatment efficacy. In this prospective clinical and molecular study, we will perform an in-depth analysis of the potential role of FMT in the context of immunotherapy.

Eligibility

Min Age: 18 Years

Inclusion Criteria9

A histologically confirmed diagnosis of malignancy.
Patients over the age of 18.
Patients planning to be treated with chemotherapy, immune checkpoint inhibitors and/or targeted therapy.
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
Able to provide written informed consent.
A histologically confirmed diagnosis of malignancy.
Over the age of 18.
Treated with immune checkpoint inhibitors and with a full response.
Currently attending medical follow-ups

Exclusion Criteria25

Severe or life-threatening food allergy (e.g. nuts, seafood)
Allergy or other contraindication to omeprazole, investigational medicinal product.
Treatment with pre- or probiotics in the four weeks prior to randomization.
Severe immunodeficiency:
Systemic chemotherapy \<30 days from baseline
Known neutropenia with absolute neutrophils \<1.0x109 cells/µL
Prolonged treatment with corticosteroids (equivalent to prednisone \>60mg daily for \>30 days) within 8 weeks of randomization
Swallowing disorder, oral-motor discoordination, inability to swallow capsules
Pregnant or breastfeeding or expecting to conceive or father children within the trial's projected duration, starting from the pre-screening or screening visit through to 120 days after the last dose of trial treatment.
Has not consumed any antimicrobials within the past 3 months
No prior exposure to HIV or viral hepatitis or suffering from tuberculosis/latent tuberculosis
No risk factors for blood-borne viruses, including high-risk sexual behavior, use of illicit drugs, any tattoo/body piercing/needlestick injury/blood transfusion/acupuncture, all within the past 6 months
No signs or symptoms consistent with Coronavirus disease 19 (COVID-19) or a nose/throat and/or stool sample with detectable Coronavirus disease 2 (CoV-2)
Has not received a live attenuated vaccine within the past 6 months
No underlying gastrointestinal conditions/symptoms (e.g., history of IBD, irritable bowel syndrome (IBS), chronic diarrhea, chronic constipation, coeliac disease, bowel resection or bariatric surgery)
No acute diarrhea/gastrointestinal symptoms within the 2 weeks prior to donating
No family history of any significant gastrointestinal conditions (e.g., family history of inflammatory bowel disease (IBD) or colorectal cancer)
No history of atopy (e.g., asthma, eosinophilic disorders)
Does not suffer from any systemic autoimmune conditions
Does not start any new treatment regimens within 2 weeks of fecal collection
No neurological or psychiatric conditions or known risk for prion disease
No history of chronic pain syndromes, including chronic fatigue syndrome and fibromyalgia
No history of receiving growth hormone, insulin from cows or clotting factor concentrates
Has not received an experimental drug or vaccine within the past 6 months
No history of travel to tropical countries within the past 6 months

Interventions

DRUGAntibiotics

Recipients will undergo bowel preconditioning with antibiotics (Rifaximin) following randomization.

OTHERFMT (Fecal Microbiota Transplantation)

FMT involves the transplantation of fecal bacteria from a screened donor to a recipient. This will be achieved per os in the form of a capsule containing freeze-dried stool obtained from the donor.