Protocolnummer: NCT05251389

FMT-trial

Een aantal maanden geleden is in het NKI-AVL de FMT-trial geopend voor het behandelen van patiënten. Binnen deze fase Ib/IIa-studie kunnen melanoom patiënten die progressief zijn onder anti-PD-1 immuuntherapie een feces microbiota transplantatie (FMT) krijgen, met als doel alsnog een respons op de immuuntherapie op te wekken. Hierbij zullen FMTs van anti-PD-1 “responding” donoren worden vergeleken met FMTs van “non-responding” donoren. Patiënten kunnen verwezen worden voor deelname aan deze studie.

Ziekenhuizen

  • Antoni van Leeuwenhoek (NKI) ziekenhuis Amsterdam

Doel van het onderzoek

To investigate whether transfer of the microbiota of either responder or non-responder patients via fecal microbiota transplantation (FMT) can convert the response to immunotherapy in anti-PD-1 refractory melanoma patients.

Behandeling

Fecal microbiota transplantation (FMT) via gastroscopy. Pre-treatment before FMT includes vancomycin 250mg four times daily for 4 days (day -5 up until day -2) and bowel clearance with MoviPrep on day -1. Anti-PD-1 treatment will be continued according to the patient’s regular treatment schedule.

stage III or IV. In case of stage IV disease, only patients with M1a or M1b disease are eligible.

Belangrijkste in/exclusiecriteria

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.

Inclusiecriteria

  • Patients have confirmed disease progression (≥20% increase according to RECIST1.1 or measurable recurrence) 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
  • 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

Exclusiecriteria:

  • 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 (prednisone ≤10mg/day or equivalent are permitted), 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 (prednisone ≤10mg/day or equivalent are permitted)
  • 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 1 liter 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

Contactpersoon

    • Prof. dr. J.B.A.G. Haanen, NKI/AVL (j.haanen@nki.nl)
    • F.H. Burgers, MD, NKI/AVL (f.burgers@nki.nl)