FMT to Convert Response to Immunotherapy

NCT ID: NCT05251389

Last Updated: 2025-03-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-31
• Study Completion Date: 2026-08-31

Brief Summary

In this study the aim is to investigate whether transfer of the microbiota of either responder or non-responder patients via fecal microbiotica transplantation (FMT) can convert the response to immunotherapy in immune checkpoint inhibitors (ICI) refractory metastatic melanoma patients.

This is a randomized double-blind intervention phase Ib/IIa trial in ICI refractory metastatic melanoma patients receiving either FMT of an ICI responding or FMT from an ICI non-responding donor, in combination with ICI.

Following randomization, patients will receive vancomycin 250 mg, four times daily for 4 days (day -5 up until day -2), and undergo bowel clearance on day -1 (in total 1L MoviPrep). The FMT, either derived from donor group R (who showed a good response on anti-PD-1 therapy) or donor group NR (who showed progression on anti-PD-1 therapy), will be performed by a gastroenterologist using esophagogastroduodenoscopy. A total amount of 198mL (containing a total of 60 gram feces) will be used for transplantation. Anti-PD-1 treatment will be continued according to the patient's regular treatment schedule. Evaluation of safety and response to treatment will be performed.

Conditions

Melanoma Stage III; Melanoma Stage IV

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

A: FMT from an ICI non-responding donor

Patients will receive FMT from an ICI non-responding donor (defined as ≥20% increase according to RECIST 1.1 criteria within the past 3 months). Patients will continue their anti-PD-1 treatment.

Group Type: EXPERIMENTAL

Fecal microbiota transplantation

Intervention Type: OTHER

Fecal microbiota transplantation of an ICI responding or Fecal microbiota transplantation from an ICI non-responding donor, in combination with ICI.

B: FMT from an ICI responding donor

Patients will receive FMT from an ICI responding donor (defined as ≥30% decrease or disappearance of all lesions according to RECIST 1.1 criteria within the past 24 months). Patients will continue their anti-PD-1 treatment.

Group Type: EXPERIMENTAL

Fecal microbiota transplantation

Intervention Type: OTHER

Fecal microbiota transplantation of an ICI responding or Fecal microbiota transplantation from an ICI non-responding donor, in combination with ICI.

Interventions

Fecal microbiota transplantation

Fecal microbiota transplantation of an ICI responding or Fecal microbiota transplantation from an ICI non-responding donor, in combination with ICI.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Patients should be 18 years or older
• Patients have pathologically confirmed advanced stage cutaneous melanoma (stage III or IV) requiring systemic treatment with anti-PD-1

• In case of stage IV disease, only patients with M1a or M1b disease are eligible.
• Patients have confirmed disease progression (≥20% increase according to RECIST1.1) on two consecutive scans with a four week interval while on anti-PD-1 treatment, of which the second scan has to be performed within 3 weeks prior to signing informed consent.
• Patients must have measurable disease per RECIST 1.1 criteria
• Patients have an ECOG performance status of 0-1 (appendix D)
• Patients have a life expectancy of >3 months
• Patients have adequate organ function as determined by standard-of-care pre-checkpoint inhibitor infusion lab (including serum ALAT/ASAT less than three times the upper limit of normal (ULN); serum creatinine clearance 50ml/min or higher; total bilirubin less than or equal to 20 micromol/L, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 50 micromol/L)
• Patients have an LDH level of ≤1 times ULN
• Patients of both genders must be willing to use a highly effective method of birth control during treatment
• Patients must be able to understand and sign the Informed Consent document

Exclusion Criteria

• Patients with acral, uveal or mucosal melanoma, or patients with an unknown primary
• Patients who have received treatment for their melanoma other than anti-PD-1 treatment.
• Stage IV patients with M1c or M1d disease.
• Patients with autoimmune diseases: patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, are excluded from this study (except Hashimoto thyroiditis, vitiligo, history of psoriasis, but no active disease)
• Patients with any grade 3 or 4 immune-related adverse events still requiring active immunosuppressive medication, apart from endocrinopathies that are stable under hormone replacement therapy. Patients who had developed grade 3-4 immune related toxicity, which has reverted to grade I with immunosuppressive drugs and who are off immunosuppression at least two weeks prior to enrollment are eligible
• Patients with brain or LM metastasis.
• Patients with an elevated LDH level
• Patients that have undergone major gastric/esophageal/bowel surgery (like Wipple, subtotal colectomy)
• Severe food allergy (e.g. nuts, shellfish)
• Patients with a swallowing disorder or expected bowel passage problems (ileus, fistulas, perforation)
• Severe dysphagia with incapability of swallowing 2 liters of bowel lavage
• Patients with a life expectancy of less than three months
• Patients with severe cardiac or pulmonary comorbidities (per judgement of the investigator)
• Women who are pregnant or breastfeeding
• Patients with any active systemic infections, coagulation disorders or other active major medical illnesses
• Patients with other malignancies, except adequately treated and a cancer-related life-expectancy of more than 5 years
• Patients who received treatment with antibiotics in the three months prior to study enrolment, or patients we are expected to receive systemic antibiotics during the course of this study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Netherlands Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John Haanen, Prof

Role: PRINCIPAL_INVESTIGATOR

Medical Oncologist

Locations

Antoni van Leeuwenhoek

Amsterdam, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

John Haanen, Prof

Role: CONTACT

j.haanen@nki.nl

+31205129111

Femke Burgers, MD

Role: CONTACT

f.burgers@nki.nl

+31205129111

Facility Contacts

Femke Burgers

Role: primary

f.burgers@nki.nl

+31 20 512 9111

References

Borgers JSW, Burgers FH, Terveer EM, van Leerdam ME, Korse CM, Kessels R, Flohil CC, Blank CU, Schumacher TN, van Dijk M, Henderickx JGE, Keller JJ, Verspaget HW, Kuijper EJ, Haanen JBAG. Conversion of unresponsiveness to immune checkpoint inhibition by fecal microbiota transplantation in patients with metastatic melanoma: study protocol for a randomized phase Ib/IIa trial. BMC Cancer. 2022 Dec 30;22(1):1366. doi: 10.1186/s12885-022-10457-y.

Reference Type: DERIVED

PMID: 36585700 (View on PubMed)

Other Identifiers

N21FMT

Identifier Type: -

Identifier Source: org_study_id