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AzTrials

Metastatic Lung CancerPhase 2NCT05502913

Fecal Microbiota Transplantation With Immune Checkpoint Inhibitors in Lung Cancer

A Phase 2 study testing Antibiotics and FMT (Fecal Microbiota Transplantation) in people with Metastatic Lung Cancer, run by Soroka University Medical Center at 2 sites in Israel.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Lung Cancer
What is being tested?
Antibiotics and FMT (Fecal Microbiota Transplantation)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
2 sitesIsrael
Study dates
1 Sep 2023to 30 Jun 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.
  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
  1. Swallowing disorder, oral-motor discoordination, inability to swallow capsules
  2. 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

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Ismaell Massalha, M.D. contact

+972526995934

ismaell@post.bgu.ac.il

Amichay Meirovitz, Prof. contact

+972528805922

amichaym@gmail.com

Israel2 sites, 2 recruiting

  • Soroka Medical Center

    Beersheba

    Ismaell Massalha, M.D.

    Recruiting

  • Rabin Medical Center

    Petah Tikva

    Mor Moskovitz, MD

    Not yet recruiting

Other trials in Israel

About this study

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

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.

Read the detailed description

Only a small subset of tumor types benefit from immune checkpoint inhibitor therapy, where most responders eventually develop resistance. Oral administration of Fecal Microbiota Transplantation (FMT) from treatment-responsive patients has been found to considerably improve Programmed death-ligand 1 (PD-L1)-based immunotherapy outcomes as well as inhibit tumor growth through augmented dendritic cell and T cell responses.

This study aims to investigate the safety and efficacy of FMT treatment combined with first-line (chemo-)immunotherapy in metastatic lung cancer. The study will include a thorough microbiome composition analysis of FMT donors and recipients to be correlated to clinical outcomes. In addition, blood samples will be analyzed using a novel commensal antigen microarray for rapid serum profiling.

Patients with metastatic malignancy who completely respond to immunotherapy will serve as the fecal implant donors. Dr. Arik Segal's Lab will produce capsules with one donor/capsule. In an open-label approach, patients will receive FMT on the first day of (chemo-)immunotherapy cycle one and every 3-4 weeks based on the specific (chemo-)immunotherapy protocol. Before FMT treatment, participants will receive active antibiotics. The second arm will receive standard-of-care treatment only. Study participants will be evaluated throughout the study using imaging, laboratory, vital signs, and disease status assessments until the end of the study.

Stool samples from study participants will be collected before the start of treatment during the (chemo-)immunotherapy cycle and at the end of treatment for sequencing and bioinformatics analysis of the microbiome. Blood samples will be collected from all donors at the study start and from all recipients at recruitment, on the day of each FMT administration, and at the end of treatment.

Statistics:

A one-sided test for differences in proportions and type I error of 0.05 will have a power of 88% to detect a 30% difference in response between the FMT and placebo group, for a total of 80 randomized patients, 40 in each treatment group stratified by PD-L1 status.

Being tested
Antibiotics, FMT (Fecal Microbiota Transplantation)
Keywords
Fecal microbiome transplant, Metastatic lung cancer
Medical subject headings
Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AntibioticsDrug

    Also called Rifaximin

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

  • 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.

Study groups in NCT05502913
Study groupRoleWhat they receive
standard of care (SoC) (IO±CTX) + FMTExperimentalSubjects 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)
Receives: Drug: Antibiotics; Other: FMT (Fecal Microbiota Transplantation)
standard-of-care treatmentNo interventionSubjects will receive standard-of-care treatment only.

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: up to 2 years

Secondary outcomes (6)

  1. Overall Survival (OS)

    OS is defined as the time passed from randomization until death from any cause.

    Measured: up to 4 years

  2. Objective response rate (ORR)

    ORR is defined as the percentage of subjects who had a complete response (CR) or partial response (PR), as defined by ir-RECIST v1.1, and is based on the best response obtained.

    Measured: From randomization (Day 0) until end of study

  3. Rate of Disease Control

    Rate of Disease Control is defined as the percentage of subjects who had a complete response (CR), partial response (PR), or stable disease (SD), as defined by ir-RECIST v1.1.

    Measured: up to 2 years

  4. Microbiome analysis

    Microbiome analysis of the stool of donors and recipients (before and after FMT) to reveal the optimum microbiome-based components to significantly increase cancer immunotherapy efficacy

    Measured: up to 2 years

  5. Serum antibody levels and lymphocyte subpopulation distribution

    Analysis of serum antibodies and blood lymphocyte repertoires to be correlated to gut microbes and yeasts via blood samples of donors and recipients at several timepoints prior and post FMT induction

    Measured: up to 2 years

  6. Safety and feasibility

    Number of adverse events and serious adverse events related definitely to fecal microbiota transplantation (FMT).

    Measured: up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Aug 2022
  2. Study start1 Sep 2023
  3. Primary completion30 Jun 2025 (estimated)
  4. Study completion30 Jun 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
80 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05502913
Sponsor's protocol ID
sor 0173-21 ctil
Status last verified
Sep 2023
First submitted
8 Aug 2022
Last updated
2 Oct 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 32732879

  • 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.

    PubMed 30458058

  • 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.

    PubMed 33542131

  • 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.

    PubMed 33303685

  • 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.

    PubMed 29097493

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Antibiotics and FMT (Fecal Microbiota Transplantation) in people with Metastatic Lung Cancer, run by Soroka University Medical Center at 2 sites in Israel.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 2 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Ismaell Massalha, M.D. (+972526995934, ismaell@post.bgu.ac.il), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) (time frame: up to 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05502913, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2023.

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