Fecal Microbiota Transplantation With Immune Checkpoint Inhibitors in Lung Cancer

• Status: Not yet recruiting
• Trial end date: 2028-06-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Soroka University Medical Center
• Collaborators: Biotax Labs LTD; Israel Cancer Association
• Treatments: Anti-Bacterial Agents; Antibiotics, Antitubercular

Criteria

Patient (Recipient) Inclusion Criteria:

1. A histologically confirmed diagnosis of malignancy.

2. Patients over the age of 18.

3. Patients planning to be treated with chemotherapy, immune checkpoint inhibitors and/or targeted therapy.

4. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

5. Able to provide written informed consent.

Patient (Recipient) Exclusion Criteria:

1. Severe or life-threatening food allergy (e.g. nuts, seafood)

2. Allergy or other contraindication to omeprazole, investigational medicinal product, or placebo ingredients

3. Treatment with pre- or probiotics in the four weeks prior to randomization.

4. 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

5. Swallowing disorder, oral-motor discoordination, inability to swallow capsules

6. 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.

Donor Inclusion Criteria:

1. A histologically confirmed diagnosis of malignancy.

2. Over the age of 18.

3. Treated with immune checkpoint inhibitors and with a full response.

4. Currently attending medical follow-ups

Donor Exclusion Criteria:

1. Has not consumed any antimicrobials within the past 3 months

2. No prior exposure to HIV or viral hepatitis or suffering from tuberculosis/latent tuberculosis

3. 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

4. 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)

5. Has not received a live attenuated vaccine within the past 6 months

6. 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)

7. No acute diarrhea/gastrointestinal symptoms within the 2 weeks prior to donating

8. No family history of any significant gastrointestinal conditions (e.g., family history of inflammatory bowel disease (IBD) or colorectal cancer)

9. No history of atopy (e.g., asthma, eosinophilic disorders)

10. Does not suffer from any systemic autoimmune conditions

11. Does not start any new treatment regimens within 2 weeks of fecal collection

12. No neurological or psychiatric conditions or known risk for prion disease

13. No history of chronic pain syndromes, including chronic fatigue syndrome and fibromyalgia

14. No history of receiving growth hormone, insulin from cows or clotting factor concentrates

15. Has not received an experimental drug or vaccine within the past 6 months

16. No history of travel to tropical countries within the past 6 months