FMT to Convert Response to Immunotherapy
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorThe Netherlands Cancer Institute
About this 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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)
Trial design
Design model
Parallel
Treatments tested in this trial
Fecal microbiota transplantation
Other interventionFecal microbiota transplantation of an ICI responding or Fecal microbiota transplantation from an ICI non-responding donor, in combination with ICI.
Treatment groups
24 Participants
are divided into 2 treatment groupsGroup A: A: FMT from an ICI non-responding donorExperimental treatment 1 intervention
Group B: B: FMT from an ICI responding donorExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Efficacy, defined as clinical benefit (stable disease (SD), partial response (PR), complete response (CR)
Time frame
At 12 weeks after FMTSecondary outcomes
1
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 FMT2
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
Time frame
Up to one year post-FMT3
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.
Time frame
At screening, and 2 weeks, 6 weeks, 12 weeks and 16 weeks after FMT4
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.
Time frame
At screening, and 2 weeks, 6 weeks, 12 weeks and 16 weeks after FMTSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov