Clinical trial NCT03686202: Feasibility Study of MET-4: Evaluating Fecal Microbiome Effects in Immunotherapy Patients
Official title: Feasibility Study of Microbial Ecosystem Therapeutics (MET-4) to Evaluate Effects of Fecal Microbiome in Patients on ImmunOtherapy (MET4-IO)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: All Solid Tumors
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: NuBiyota
First posted: 2018-09-26
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is designed to assess the safety, tolerability and engraftment (cumulative relative abundance) of MET-4 strains when given in combination with immune checkpoint inhibitors (ICIs). There will be a safety cohort (group A) of 5 subjects which will receive MET-4 in addition to standard of care (SOC) ICI. After the safety cohort, 40 patients will be enrolled in group B which will be randomized to MET4 with SOC ICI vs. control group with SOC ICI only. Group C will enroll 20 patients who have already started on SOC ICI and have had first unconfirmed progression of disease and expected to continue with standard ICI treatment. These patients will be randomized to continue receiving standard ICI alone, or SOC ICI with MET4.

Detailed description: Human associated microorganisms (the microbiota) inhabit virtually all surfaces of the human body. The gut is densely colonized by the microbiota which aids in the digestion. Animal and human observational and experimental evidence show a link between gut microbiota and the activation, regulation and function of the immune system. Pre-clinical studies in mouse models have linked the gut microbiota to efficacy of anticancer therapies. Microbial Ecosystem Therapeutics (MET) is a new treatment approach developed as an alternative to fecal transplantation. MET consists of a defined mixture of pure live cultures of intestinal bacteria isolated from a stool sample of a healthy donor.

This study is designed to assess the safety, tolerability and engraftment (cumulative relative abundance) of MET-4 strains when given in combination with immune checkpoint inhibitors (ICIs).

Eligibility criteria: Inclusion Criteria:

* Signed written and voluntary informed consent
* Age \>=18 years, male or female
* Histologically or cytological documented locally-advanced or metastatic solid malignancy which is incurable.
* Group A: Is already on treatment with monotherapy anti-PD-1 or PD-L1 immune checkpoint inhibitor, not in the context of a therapeutic clinical trial.

Group B: Is intended to start on treatment with monotherapy anti-PD-1 or PD-L1 immune checkpoint inhibitors as considered appropriate by treatment physician, and not in the context of a therapeutic clinical trial.

Group C: Is already on treatment with monotherapy anti-PD-1 or PD-L1 immune checkpoint inhibitor, not in the context of a therapeutic clinical trial with first unconfirmed PD on evaluation scan per investigator's assessment.

* Be willing to provide 10-15 unstained slides of archival tissue sample. Subjects who decline or have not sufficient archived tissue samples may still enroll if all other criteria are eligible.
* Be willing and able to provide stool and blood specimen for analyses at protocol specified time points.
* Have measurable disease based on RECIST 1.1
* Performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) performance scale.
* Prior therapy with any immunotherapy allowed.
* Not pregnant for females of child bearing potential as indicated by negative serum or urine pregnancy test within 72 hours of study start.

Exclusion Criteria:

* Subjects unable to swallow orally administered medications or any subjects with gastrointestinal disorders likely to interfere with absorption (e.g. bowel obstruction, short gut syndrome, blind loop syndrome, ileostomy etc). Subjects with colostomies may be enrolled.
* Any condition that, in the opinion of the Investigator, would interfere with subject safety, or evaluation of the collected specimen and interpretation of study result.
* Pregnant or planning to get pregnant in the next 6 months.

Primary outcomes:
measure: Cumulative relative abundance of immunotherapy-responsiveness associated species at day 12 of MET-4
timeFrame: Approximately 12 days
measure: Changes in relative abundance of immunotherapy-responsiveness associated MET-4 strains between baseline and approximately day 12
timeFrame: Approximately 12 days
measure: Number of participants with treatment-related adverse events assessed by CTCAE v.5.0
timeFrame: 2 years
Secondary outcomes:
measure: Cumulative relative abundance of immunotherapy-responsiveness associated species at later MET-4 or control time points (approximately 24 weeks and/or 1-2 weeks following the end of treatment).
timeFrame: 2 years
measure: Changes in relative abundance of immunotherapy-responsiveness associated MET-4 strains between baseline and later MET-4 or control timepoints (approximately 24 weeks and/or 1-2 weeks following the end of treatment)
timeFrame: 2 years
measure: Bacterial taxonomic diversity between baseline and follow-up samples
timeFrame: 2 years
Other outcomes:
measure: Response
timeFrame: 2 years
measure: Progression free survival
timeFrame: 2 years
measure: Changes in immune cell subsets in the systemic circulation in response to MET-4 through serial blood sampling.
timeFrame: 24 weeks
measure: Characterization of tumor microenvironment of archived tumor samples
timeFrame: 2 years
measure: Dynamic measures of microbiome as correlates of blood immune profiling
timeFrame: 2 years
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Princess Margaret Cancer Centre
name: Lillian Siu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Princess Margaret Cancer Centre
name: Anna Spreafico, MD
role: PRINCIPAL_INVESTIGATOR
References: