FMT to Convert Response to Immunotherapy

Launched by THE NETHERLANDS CANCER INSTITUTE · Feb 11, 2022

Keywords

ClinConnect Summary

This clinical trial is investigating whether fecal microbiota transplantation (FMT) can help patients with advanced melanoma who have not responded to standard immunotherapy treatments. The study will compare the effects of FMT from patients who responded well to immunotherapy against FMT from those who did not respond. Participants will receive FMT along with their regular treatment, and researchers will monitor how well the treatment works and any side effects that may occur.

To be eligible for this trial, participants must be at least 18 years old and have advanced melanoma (stage III or IV) that has continued to progress despite receiving anti-PD-1 therapy. Other criteria include having measurable disease and an overall good health status. Participants can expect to undergo a bowel preparation process before receiving the FMT, which will be administered by a specialist using a safe procedure. The trial is actively recruiting, and both men and women are welcome to participate, provided they meet the necessary health requirements.

Gender

ALL

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