Fecal Microbiota Transplantation With Immune Checkpoint Inhibitors in Lung Cancer

NCT05502913 | Recruiting Phase 2

• 1 other identifier: sor 0173-21 ctil
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Metastatic Lung Cancer

Keywords

Fecal microbiome transplant; Metastatic lung cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  PFS is defined as the time passed from screening until the date of progressive disease (PD) or death from any cause. Imaging will be performed using computed tomography (CT) and/or Positron emission tomography (PET).

  up to 2 years

Secondary Outcomes (6)

• Overall Survival (OS)

  up to 4 years

• Objective response rate (ORR)

  From randomization (Day 0) until end of study

• Rate of Disease Control

  up to 2 years

• Microbiome analysis

  up to 2 years

• Serum antibody levels and lymphocyte subpopulation distribution

  up to 2 years

Study Arms (2)

standard of care (SoC) (IO±CTX) + FMT

EXPERIMENTAL

Subjects assigned to Arm 1 will be required to swallow FMT capsules in a regimen of ten capsules in the morning and ten capsules in the afternoon on day 1 of the first (chemo-)immunotherapy cycle, and then every three weeks. abbreviation: Immuno-Oncology (IO) Chemotherapy (CTX)

Drug: Antibiotics; Other: FMT (Fecal Microbiota Transplantation)

standard-of-care treatment

NO INTERVENTION

Subjects will receive standard-of-care treatment only.

Interventions

Antibiotics DRUG

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

Also known as: Rifaximin

standard of care (SoC) (IO±CTX) + FMT

FMT (Fecal Microbiota Transplantation) OTHER

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.

standard of care (SoC) (IO±CTX) + FMT

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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
• Has not consumed any antimicrobials within the past 3 months
• No prior exposure to HIV or viral hepatitis or suffering from tuberculosis/latent tuberculosis

Sponsors & Collaborators

• Soroka University Medical Center: lead
• Biotax Labs LTD: collaborator
• Israel Cancer Association: collaborator

Study Sites (2)

Soroka Medical Center

Beersheba, Israel

RECRUITING

Rabin Medical Center

Petah Tikva, Israel

NOT YET RECRUITING

Related Publications (5)

• Robert C. A decade of immune-checkpoint inhibitors in cancer therapy. Nat Commun. 2020 Jul 30;11(1):3801. doi: 10.1038/s41467-020-17670-y.

  PMID: 32732879 BACKGROUND

• Chen D, Wu J, Jin D, Wang B, Cao H. Fecal microbiota transplantation in cancer management: Current status and perspectives. Int J Cancer. 2019 Oct 15;145(8):2021-2031. doi: 10.1002/ijc.32003. Epub 2018 Dec 30.

  PMID: 30458058 BACKGROUND

• Davar D, Dzutsev AK, McCulloch JA, Rodrigues RR, Chauvin JM, Morrison RM, Deblasio RN, Menna C, Ding Q, Pagliano O, Zidi B, Zhang S, Badger JH, Vetizou M, Cole AM, Fernandes MR, Prescott S, Costa RGF, Balaji AK, Morgun A, Vujkovic-Cvijin I, Wang H, Borhani AA, Schwartz MB, Dubner HM, Ernst SJ, Rose A, Najjar YG, Belkaid Y, Kirkwood JM, Trinchieri G, Zarour HM. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. Science. 2021 Feb 5;371(6529):595-602. doi: 10.1126/science.abf3363.

  PMID: 33542131 BACKGROUND

• Baruch EN, Youngster I, Ben-Betzalel G, Ortenberg R, Lahat A, Katz L, Adler K, Dick-Necula D, Raskin S, Bloch N, Rotin D, Anafi L, Avivi C, Melnichenko J, Steinberg-Silman Y, Mamtani R, Harati H, Asher N, Shapira-Frommer R, Brosh-Nissimov T, Eshet Y, Ben-Simon S, Ziv O, Khan MAW, Amit M, Ajami NJ, Barshack I, Schachter J, Wargo JA, Koren O, Markel G, Boursi B. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science. 2021 Feb 5;371(6529):602-609. doi: 10.1126/science.abb5920. Epub 2020 Dec 10.

  PMID: 33303685 BACKGROUND

• Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, Prieto PA, Vicente D, Hoffman K, Wei SC, Cogdill AP, Zhao L, Hudgens CW, Hutchinson DS, Manzo T, Petaccia de Macedo M, Cotechini T, Kumar T, Chen WS, Reddy SM, Szczepaniak Sloane R, Galloway-Pena J, Jiang H, Chen PL, Shpall EJ, Rezvani K, Alousi AM, Chemaly RF, Shelburne S, Vence LM, Okhuysen PC, Jensen VB, Swennes AG, McAllister F, Marcelo Riquelme Sanchez E, Zhang Y, Le Chatelier E, Zitvogel L, Pons N, Austin-Breneman JL, Haydu LE, Burton EM, Gardner JM, Sirmans E, Hu J, Lazar AJ, Tsujikawa T, Diab A, Tawbi H, Glitza IC, Hwu WJ, Patel SP, Woodman SE, Amaria RN, Davies MA, Gershenwald JE, Hwu P, Lee JE, Zhang J, Coussens LM, Cooper ZA, Futreal PA, Daniel CR, Ajami NJ, Petrosino JF, Tetzlaff MT, Sharma P, Allison JP, Jenq RR, Wargo JA. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018 Jan 5;359(6371):97-103. doi: 10.1126/science.aan4236. Epub 2017 Nov 2.

  PMID: 29097493 BACKGROUND

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Anti-Bacterial Agents; Rifaximin; Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Biological Therapy; Therapeutics

Study Officials

• Ismaell Massalha, MD

  Soroka University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ismaell Massalha, M.D.

CONTACT

+972526995934; ismaell@post.bgu.ac.il

Amichay Meirovitz, Prof.

CONTACT

+972528805922; amichaym@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2022
• First Posted: August 16, 2022
• Study Start: September 1, 2023
• Primary Completion: June 30, 2025
• Study Completion (Estimated): June 30, 2028
• Last Updated: October 2, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

IL (2)