Conversion of unresponsiveness to immunotherapy by Fecal Microbiota Transplantation in patients with metastatic melanoma and non-melanoma skin cancer: a randomized phase Ib/IIa trial
- Conditions
- melanomaskin cancer10040900
- Registration Number
- NL-OMON52200
- Lead Sponsor
- Antoni van Leeuwenhoek Ziekenhuis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 28
- Patients should be 18 years or older
- Patients have pathologically confirmed advanced stage cutaneous melanoma
cutaneous squamous cell carcinoma or Merkel cell carcinoma (stage III or IV)
requiring systemic treatment with anti-PD-(L)1
- In case of melanoma patients with stage IV disease, only patients
with limited disease progression without immediate clinical risks of delaying
other treatment options, based on the judgment of the treating physician, are
eligible.
- Patients have confirmed disease progression (>=20% increase according to
RECIST 1.1 or measurable recurrence under adjuvant treatment) 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 <2x 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
- Patients with acral, uveal or mucosal melanoma.
- Patients with non-cutaneous squamous cell carcinoma
- Patients who have received systemic treatment for their melanoma or
non-melanoma skin cancer other than anti-PD-(L)1 treatment.
- Stage IV melanoma patients with rapid or invasive disease progression
necessitating an immediate switch to a proven effective treatment, as judged by
the treating physician.
- 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 active or symptomatic brain metastasis or LM metastasis (brain
metastases treated with radiotherapy, that are inactive and asymptomatic are
allowed).
- 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
- 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>For the efficacy analysis the primary endpoint will be clinical benefit (SD,<br /><br>PR, CR) at 12 weeks, confirmed on a second scan after 4 weeks. </p><br>
- Secondary Outcome Measures
Name Time Method <p>For the safety analysis the endpoint will be occurrence of toxicity of grade 3<br /><br>or higher (secondary endpoint). </p><br>