Preventing Toxicity in Renal Cancer Patients Treated With Immunotherapy Using Fecal Microbiota Transplantation (PERFORM)
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|ClinicalTrials.gov Identifier: NCT04163289|
Recruitment Status : Recruiting
First Posted : November 14, 2019
Last Update Posted : September 3, 2020
Cancer immunotherapy has been largely adopted in oncology patient management in the last decade. The deep and long responses to immunotherapy have accelerated the approval of these drugs across multiple disease sites. However, these agents can also be toxic to patients, meaning, the patient will have to discontinue treatment and outcomes could be negatively affected. Recently, a combination of two immunotherapy drugs, ipilimumab and nivolumab (ipi/nivo), has been approved for the treatment of intermediate and poor-risk renal cell carcinoma (RCC) patients. This powerful combination provides survival benefit, however, it can also be highly toxic leading to discontinuation of this treatment.
There has been some evidence that these otherwise toxic drugs can be better tolerated by altering the composition of the patients gut bacteria to create a more diverse and healthy microbiome. The current study will involve Fecal Microbiota Transplantation (FMT) before the start of the immunotherapy combination, and during the first two cycles of ipilimumab treatment (the more toxic agent) as supportive therapy to prevent toxicity associated with the ipi/nivo combination.
The goal of this project is to study the safety of such FMT combination treatment and reduce occurrence of immune-related toxicities in patients, allowing them to continue their cancer treatments in the hopes of a better outcome. The investigators will also be looking at changes in the immune populations, microbiome profile of patients, response to treatment, and patient survival as secondary objectives.
|Condition or disease||Intervention/treatment||Phase|
|Renal Cell Carcinoma||Drug: Fecal Microbiota Transplantation||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Preventing Immune-Related Adverse Events in Renal Cell Carcinoma Patients Treated With Combination Immunotherapy Using Fecal Microbiota Transplantation|
|Actual Study Start Date :||January 23, 2020|
|Estimated Primary Completion Date :||March 2024|
|Estimated Study Completion Date :||November 2028|
Experimental: Fecal Microbiota Transplantation
Fecal microbiota transplantation combined with approved standard of care treatment with nivolumab and ipilimumab.
Drug: Fecal Microbiota Transplantation
Fecal microbiota transplantation is the process of administering stool samples derived from healthy donors, which have been processed and prepared into capsules. Capsules will be taken 7 days or more prior to the first treatment with nivolumab and ipilimumab, and 1 to 3 days prior to the next 2 treatments with nivolumab and ipilimumab.
- Occurence of immune-related colitis associated with ipilimumab/nivolumab treatment [ Time Frame: 28 months ]Occurence of grade 3 or higher immune-related colitis from the start of treatment with ipilimumab and nivolumab to 120 days after completion of treatment. Colitis will be graded using the Common Toxicity Criteria for Adverse Events version 4.02.
- Incidence of any immune-related adverse event associated with ipilimumab/nivolumab treatment [ Time Frame: 28 months ]Incidence of any immune-related adverse event grade 3 or higher from the start of treatment with ipilimumab and nivolumab to 120 days after completion of treatment. Adverse events will be graded using the Common Toxicity Criteria for Adverse Events version 4.02.
- Proportion of patients who discontinue treatment because of immune-related adverse events [ Time Frame: 28 months ]Measured from the start of treatment with ipilimumab and nivolumab to 120 days after completion of treatment.
- Objective response rate [ Time Frame: Approximately 9 years (end of study) ]Objective response rate is defined as the proportion of patients achieving a complete response (disappearance of all lesions) and a partial response (30% or more decrease in the sum diameters of the target lesions) (Eisenhauer et al., 2009). Objective response rate will be measured using RECIST criteria version 1.1.
- Changes in patient microbiome following FMT [ Time Frame: At baseline (prior to FMT) and prior to the 1st, 2nd, 3rd and fourth dose of immunotherapy (approximately 1 week, 3 weeks, 7 weeks , and 10 weeks post FMT). ]Changes in patient microbiome will be determined by analysis of gut bacterial composition in patient stool samples at baseline and post-FMT.
- Success rate of the fecal microbiota transplant [ Time Frame: At baseline (prior to FMT) and prior to the 1st, 2nd, 3rd and fourth dose of immunotherapy (approximately 1 week, 3 weeks, 7 weeks , and 10 weeks post FMT). ]Success will be determined by comparing the make-up of the healthy donor microbiome to the patient's microbiome, using stool samples.
- Determine the effect on immune response [ Time Frame: At baseline (prior to FMT) and prior to the 1st, 2nd, 3rd and fourth dose of immunotherapy (approximately 1 week, 3 weeks, 7 weeks , and 10 weeks post FMT). ]Effects on the patient immune response will be assessed by examining changes in peripheral blood immune cells, chemokines, cytokines, and other immune and tumor biomarkers.
- Health related quality of life [ Time Frame: 30 months ]Patient reported quality of life will be measured using the standardized questionnaire, European Organization for Research and Treatment of Cancer (EORTC) EQ-5D-5L.
- Progression-free survival [ Time Frame: Approximately 7 years ]The time from registration to death from any cause, or first recurrence of tumor at any site.
- Overall survival [ Time Frame: Approximately 7 years ]The time from registration to the time of death from any cause.
- Assess the immune profile of the tumor [ Time Frame: At baseline (prior to FMT) and between weeks 7 and 10. ]Tumor tissue will be collected at various timepoints, and will be used to examine the immune profile and changes of various genes in the tumor.
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): NCT04163289
|Contact: Ricardo Fernandes, MD||519-685-8640||Ricardo.Fernandes@lhsc.on.ca|
|London Regional Cancer Program of the Lawson Health Research Institute||Recruiting|
|London, Ontario, Canada, N6A 5W9|
|Contact: Ricardo Fernandes, MD 519-685-8640 Ricardo.Fernandes@lhsc.on.ca|
|Principal Investigator:||Ricardo Fernandes, MD||Lawson Health Research Institute|
|Principal Investigator:||Saman Maleki, PhD||Lawson Health Research Institute|