Immunotherapy has helped many cancer patients in the last 5 years by enhancing a patient's immune system to fight cancer. Anti-Programmed Death (PD-1) immunotherapy drugs such as pembrolizumab and nivolumab remove the breaks from cancer-fighting immune cells and have been effective in treating some melanoma patients. Despite the major breakthrough of immunotherapy in oncology treatment, many patients do not respond to this new class of anti-cancer drugs. Recently, evidence suggests that the microorganisms living in a patient's intestines play a major role in modifying the response to anti-PD-1drugs. Patients who respond to these drugs have a unique and healthy group of microorganisms in their gut. Therefore, positive modification of a cancer patient's gut microorganisms to create a more diverse and healthy microbiome may improve the response to immunotherapy. One method of modifying the microbiome is Fecal Microbial Transplantation (FMT) that is already being successfully used in the clinic to treat non-cancer patients with persistent bacterial infections. In this study, the investigators will combine FMT with the approved immunotherapy drugs pembrolizumab or nivolumab that are the standard of care for the treatment of advanced melanoma. The purpose of this study is to examine the safety of combining these two therapies in melanoma patients. The investigator will use fecal material from a healthy donor selected via our stringent protocol that is Health Canada approved. In addition to assessing the safety of the combination, the investigator will also study the effect of FMT on the immune system and microbial ecosystem of the gut.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
All patients in this trial will receive FMT at least one week prior to treatment with approved immunotherapy (either pembrolizumab or nivolumab). Samples for FMT are sourced at and by the microbiology group under the supervision of Dr. Silverman at St Joseph's Hospital. Donor screening procedures are described in appendix 4. Transplant will be from one single donor for all participants unless Dr. Silverman's lab considers the need for more than one donor based on availability of donors. There will be no "mixture" of donor samples. Donor samples are manufactured into capsules according to Kao et al, 2017.
London Regional Cancer Program
London, Ontario, Canada
CHUM
Montréal, Ontario, Canada
Jewish General Hospital
Montreal, Quebec, Canada
To evaluate the safety of combining Fecal Microbial Transplantation (FMT) using intestinal bacteria existing in the stool of healthy donors with immunotherapy in melanoma patients.
Toxicity assessments and concurrent medication review will occur at every visit throughout immunotherapy treatment. Any adverse events after FMT administration will be followed until resolution or until judged stable by the investigator.
Time frame: 60 months
Assess Objective Response Rate
To evaluate whether combination of FMT and immunotherapy can enhance antitumor effect in melanoma patients by assessing the objective response rate (ORR; the rate of complete response plus partial response) as per the RECIST 1.1 criteria including immune-related response criteria.
Time frame: At baseline and every 12 weeks thereafter up to 60 months
To Evaluate the effect(s) combination FMT and immunotherapy has on the gut microbiome
Stool sample for microbiome analysis will be collected in the form of used (visibly soiled) toilet paper packed in a labeled biohazard bad and brought with the participant to clinic. The stool sample can be obtained by the patient from a bowel movement up to 3 days prior to the visit.
Time frame: At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy (2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit
Evaluate the effect(s) combination FMT and immunotherapy has on changes in immune blood biomarkers
blood samples will be collected to assess changes in immune blood biomarkers before and after FMT administration by assessing Complete Blood Counts (WBC, HGB, platelets, neutrophils, lymphocytes, monocytes, eosinophils, basophils)
Time frame: At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy(2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit
Evaluate the effect(s) combination FMT and immunotherapy has on changes in immune blood biomarkers
blood samples will be collected to assess changes in immune blood biomarkers before and after FMT administration by assessing circulating T cells
Time frame: At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy(2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit
Evaluate the effect(s) combination FMT and immunotherapy has on changes in immune blood biomarkers
blood samples will be collected to assess changes in immune blood biomarkers before and after FMT administration by assessing checkpoint molecules including PD-1, PD-L1, TIM-3, LAG-3, TIGIT
Time frame: At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy(2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit
Evaluate the effect(s) combination FMT and immunotherapy has on changes in immune blood biomarkers
blood samples will be collected to assess changes in immune blood biomarkers before and after FMT administration by assessing immune markers such as HLA-DR CD38 and CD28
Time frame: At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy(2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit
Evaluate the effect(s) combination FMT and immunotherapy has on patient's metabolomics
A urine sample will be collected for metabolomics analysis.
Time frame: At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy (2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit
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