Aim of the study is to investigate the effect of Fecal Microbiota Transplantation (FMT) and Checkpoint Inhibitor (CI) re-challenge in prior CI refractory patients on Progression free survival (PFS) and tumor using donor stool of former malignant melanoma patients, who have been in remission due to CI treatment for at least 1 year.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
5
Patients receiving stool from prior malignant melanoma (MM) patients in remission for at least 1 year after Checkpoint Inhibitor Treatment.
Patients receiving their own stool in terms of sham FMT.
Medical University of Graz
Graz, Austria
Progression free survival (PFS)
Patients undergoing CI therapy after FMT will be evaluated by Immune-RECIST (iRECIST) criteria after contrast-enhanced CT-scan in order to determine disease progression.
Time frame: 3 months after checkpoint inhibitor (CI) therapy following fecal microbiota transplantation (FMT).
Tumor response (CR, PR, SD)
Complete response (CR), partial response (PR) and stable disease (SD) of target or non-target lesions are considered tumor response in this trial according to iRECIST criteria after three months.
Time frame: 3 months after checkpoint inhibitor (CI) therapy following FMT.
Detection of specific donor signaling in intestinal microbiota leading to response to CI therapy.
A total of five donors will be included in the study. The allogenic-FMT group will receive donor stool from a single donor per patient for both, the primary FMT and a scheduled booster FMT. Donors will be divided into those, who successfully improved PFS and/or tumor response versus those, who were not able to induce treatment response. Donor stool will be evaluated by 16s-RNA analysis.
Time frame: 3 months after checkpoint inhibitor (CI) therapy following FMT.
Detection of specific patients' microbiota pre and post FMT leading to response.
Patients will be divided into responders and nonresponders and microbiota will be analyzed via 16s-RNA analysis before and after FMT. We will look into specific donor-signaling in patients stool samples after FMT, as well as trying to identify groups of intestinal microbiota associated with higher response rates to CI re-challenge.
Time frame: 3 months after checkpoint inhibitor (CI) therapy following FMT.
Frequency of Adverse Events categorized according to the CTCAE grading system Version 4.0
To evaluate safety and toxicity of CI therapy after FMT vs. control group. Drug toxicity will be monitored, categorized according to the CTCAE grading system Version 4.0 and managed according to recent recommendations by the SITC Toxicity Management Working Group.
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Time frame: 3 months after checkpoint inhibitor (CI) therapy following FMT.
Serum Neutrophil-to-Lymphocyte Ratio (NLR) pre- and post-FMT as an indicator for response.
In our study we will look at potential alterations in NLR after FMT and whether this can indicate response to CI treatment after FMT.
Time frame: 3 months after checkpoint inhibitor (CI) therapy following FMT.
Detection of differences between primary and secondary non-responders to CI therapy and their specific outcome after FMT by performing a subgroup analysis.
To date and according to present data we do not know, whether primary or secondary non-responders may have a better potential to respond to FMT in order to reach PFS under CI rechallenge. Hence, a subgroup analysis will be performed, in order to identify patient groups best suited for such treatment in the future.
Time frame: 3 months after checkpoint inhibitor (CI) therapy following FMT.