Fecal Microbial Transplantation in Combination With Immunotherapy in Melanoma Patients (MIMic)
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|ClinicalTrials.gov Identifier: NCT03772899|
Recruitment Status : Recruiting
First Posted : December 11, 2018
Last Update Posted : June 27, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Melanoma||Drug: Fecal Microbial Transplantation||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Fecal Microbial Transplantation in Combination With Immunotherapy in Melanoma Patients (MIMic)|
|Actual Study Start Date :||March 27, 2019|
|Estimated Primary Completion Date :||December 2023|
|Estimated Study Completion Date :||December 2023|
- Drug: Fecal Microbial Transplantation
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.
- 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. [ Time Frame: 60 months ]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.
- Assess Objective Response Rate [ Time Frame: At baseline and every 12 weeks thereafter up to 60 months ]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.
- To Evaluate the effect(s) combination FMT and immunotherapy has on the gut microbiome [ 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 ]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.
- Evaluate the effect(s) combination FMT and immunotherapy has on changes in immune blood biomarkers [ 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 ]For study specific testing, we will also isolate lymphocytes from the peripheral blood using ficoll and examine the level of circulating CD4+ and CD8+ T cells, dividing CD8+ T cells (Ki67+CD3+CD8+ T cells), levels of checkpoint molecules including PD-1, PD-L1, TIM-3, LAG-3, TIGIT and BTLA on CD8+ T cells, and other immune markers such as HLA-DR CD38, and CD28 using flow cytometry.
- Evaluate the effect(s) combination FMT and immunotherapy has on patient's metabolomics [ 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 ]A urine sample will be collected for metabolomics analysis.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03772899
|Contact: John Lenehan, MDfirstname.lastname@example.org|
|Contact: Saman Maleki, PhD||519-685-8500 ext 55769||Saman.MalekiVareki@lhsc.on.ca|
|Principal Investigator:||John Lenehan, MD||London Regional Cancer Program|