Melanoma Stage IIIPhase 1/2NCT05251389
FMT to Convert Response to Immunotherapy
A Phase 1/2 study testing Fecal microbiota transplantation in people with Melanoma Stage III and Melanoma Stage IV, run by The Netherlands Cancer Institute at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma Stage III, Melanoma Stage IV
- What is being tested?
- Fecal microbiota transplantation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteNetherlands
- Study dates
- 31 Aug 2022to Aug 2026
- Phase
- Phase 1/2
- 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
Who may be able to join
- 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)
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- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Antoni van Leeuwenhoek
Amsterdam, 1066CX
Femke Burgers, +31 20 512 9111, f.burgers@nki.nl
About this study
Official title: Conversion of Unresponsiveness to Immunotherapy by Fecal Microbiota Transplantation in Patients With Metastatic Melanoma: a Randomized Phase Ib/IIa Trial
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
- Being tested
- Fecal microbiota transplantation
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fecal microbiota transplantationOther
Fecal microbiota transplantation of an ICI responding or Fecal microbiota transplantation from an ICI non-responding donor, in combination with ICI.
| Study group | Role | What they receive |
|---|---|---|
| A: FMT from an ICI non-responding donor | Experimental | 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. Receives: Other: Fecal microbiota transplantation |
| B: FMT from an ICI responding donor | Experimental | 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. Receives: Other: Fecal microbiota transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy, defined as clinical benefit (stable disease (SD), partial response (PR), complete response (CR)
Measured: At 12 weeks after FMT
Secondary outcomes (5)
Safety, measured as the occurrence of toxicity of grade 3 or higher
Measured: At screening, and 2 weeks, 6 weeks, 12 weeks and 16 weeks after FMT
Progression free survival (PFS)
PFS will be calculated from the date of registration to the date of progression or death, whichever occurs first, censoring patients without progression and who are still alive at last follow-up
Measured: Up to one year post-FMT
The change in gut microbiome following FMT and the duration and stability over time
To assess the fecal microbiome (which includes bacteria, archaea, viruses, parasites and fungi), nucleotides will be isolated for next generation sequencing and molecular methodologies (e.g. PCR, qPCR). Initially, whole genomic DNA (metagenomics) and the ITS2 region or the rRNA gene will be will be sequenced, giving insights in the overall microbiota's structural and functional features and in the structural features of the fungal microbiota, respectively, which both will be associated to clinical variables.
Measured: At screening, and 2 weeks, 6 weeks, 12 weeks and 16 weeks after FMT
The change in metabolome following FMT and the duration and stability over time
To assess the metabolome in feces (which includes amino acids, short lipids, sugars and nucleotides), samples will be processed and analyzed by Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) or Nuclear magnetic resonance (NMR). The identified metabolic profile will be associated with the microbiome data and clinical variables.
Measured: At screening, and 2 weeks, 6 weeks, 12 weeks and 16 weeks after FMT
The immune changes; changes in cell populations (absolute, relative, phenotypical), in chemokine/cytokine levels and in the tumor-microenvironment
Tumor biopsies and blood samples will be analyzed to investigator the local and systemic immune changes: changes in cell populations (absolute, relative, phenotypical), in chemokine/cytokine levels and in the tumor-microenvironment (TME). If possible, results will be linked to response.
Measured: At screening, and 2 weeks, 6 weeks, 12 weeks and 16 weeks after FMT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2022
- Study start31 Aug 2022
- Primary completionAug 2026 (estimated)
- Study completionAug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Melanoma Stage IIIStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- a randomized double-blind intervention trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John Haanen, Prof, Principal investigator, Medical Oncologist
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05251389
- Sponsor's protocol ID
- N21FMT
- Status last verified
- Mar 2025
- First submitted
- 20 Dec 2021
- Last updated
- 10 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36585700
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Conversion of Unresponsiveness to Immunotherapy by Fecal Microbiota Transplantation in Patients With Metastatic Melanoma: a Randomized Phase Ib/IIa Trial
- ClinicalTrials.gov ID
- NCT05251389
- Acronym / sponsor ID
- N21FMT
- Conditions
- Melanoma Stage III, Melanoma Stage IV
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Study start
- 31 Aug 2022 (actual)
- Primary completion
- Aug 2026 (estimated)
- Study completion
- Aug 2026 (estimated)
- First posted
- 22 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- a randomized double-blind intervention trial
| Arm | Type | Receives |
|---|---|---|
| A: FMT from an ICI non-responding donor | Experimental | Other: Fecal microbiota transplantationPatients 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. |
| B: FMT from an ICI responding donor | Experimental | Other: Fecal microbiota transplantationPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
- 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)
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fecal microbiota transplantationFecal microbiota transplantation of an ICI responding or Fecal microbiota transplantation from an ICI non-responding donor, in combination with ICI. | Other | A: FMT from an ICI non-responding donor, B: FMT from an ICI responding donor |
Primary outcome
Efficacy, defined as clinical benefit (stable disease (SD), partial response (PR), complete response (CR)
Time frame: At 12 weeks after FMT
5 secondary outcomes
Safety, measured as the occurrence of toxicity of grade 3 or higher
Time frame: At screening, and 2 weeks, 6 weeks, 12 weeks and 16 weeks after FMT
Progression free survival (PFS)
Time frame: Up to one year post-FMT
The change in gut microbiome following FMT and the duration and stability over time
Time frame: At screening, and 2 weeks, 6 weeks, 12 weeks and 16 weeks after FMT
The change in metabolome following FMT and the duration and stability over time
Time frame: At screening, and 2 weeks, 6 weeks, 12 weeks and 16 weeks after FMT
The immune changes; changes in cell populations (absolute, relative, phenotypical), in chemokine/cytokine levels and in the tumor-microenvironment
Time frame: At screening, and 2 weeks, 6 weeks, 12 weeks and 16 weeks after FMT
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2025.
- Derived from this study: PubMed 36585700Borgers 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
John Haanen, Prof principal investigator
Medical Oncologist
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Fecal microbiota transplantation in people with Melanoma Stage III and Melanoma Stage IV, run by The Netherlands Cancer Institute at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 17 exclusion criteria. 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 10 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 John Haanen, Prof (+31205129111, j.haanen@nki.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy, defined as clinical benefit (stable disease (SD), partial response (PR), complete response (CR) (time frame: At 12 weeks after FMT). 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 NCT05251389, which also lists 1 linked publication.
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 10 Mar 2025.