RECRUITING

Healthy-donor Microbiome MTP-101-C in Steroid Relapse/Refractory Immune-related Cutaneous Adverse Events (irCAEs) and Immune-mediated Colitis (IMC)

Conditions

Immune-mediated Colitis (IMC)Immune-related Dermatitis gut microbiome anti-PD-1 therapy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Multiple retrospective studies suggest that the administration of corticosteroids to treat irAEs is safe, and does not compromise efficacy of ICI therapy in cancer patients. While \~67% of patients respond to corticosteroids, 33% of patients require biologic therapy such as TNFα inhibitors (e.g. infliximab), integrin α4β7 inhibitors (e.g. vedolizumab), or JAK/STAT inhibitors (e.g. tofactinib). This study aims to determine that distinct pathobionts govern the development of irCAE and IMC; and that the administration of hdFMT may reverse steroid-refractory irCAEs or IMC. The use of hdFMT has been shown to be effective in steroid and biologic (TNFα and/or integrin α₄β₇ inhibitor) refractory colitis in PD-1 and/or CTLA-4 ICI treated cancer patients in single-institution case series.

Official Title

Phase II Trial of Healthy-donor Derived Full-spectrum Microbiome Therapeutic MTP-101-C in Steroid Relapse/Refractory Immune-related Cutaneous Adverse Events (irCAEs) and Immune-mediated Colitis (IMC) (FMT-ELIMINATE)

Quick Facts

Study Start:2025-01-23

Study Completion:2030-09-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06499896

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Able to swallow oral medication. * The participant provides written informed consent for the trial. * Willingness to use contraception for duration of trial participation. Male participants: A male participant must agree to use a contraception per protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period. * Receipt of high-dose systemic corticosteroids defined as 1-2mg/kg prednisone equivalent daily (either oral or intravenous) with a taper over 4-6 weeks as defined by society consensus guidelines102-105; AND * No receipt of biologic such as but not limited to (dupilumab, rituximab) prior to enrollment. * NOTE: Patients must have received steroids to be eligible. * NOTE: Steroid "resistant" disease: patients whose symptoms responded (reduction in a CTCAE grade) initially but who developed recurrence upon steroid taper or discontinuation. * NOTE: Steroid "refractory" disease: patients whose symptoms have not clinically improved by a CTCAE grade in ≥48 hours or maximum of 14 days. * Receipt of high-dose systemic corticosteroids defined as 1-2mg/kg prednisone equivalent daily (either oral or intravenous) with a taper over 4-6 weeks as defined by society consensus guidelines102-105; AND * No receipt of biologic such as but not limited to (TNFα inhibitor infliximab OR α₄β₇ integrin inhibitor vedolizumab) prior to enrollment. * Patients must have received steroids to be eligible. * Steroid "resistant" disease: patients whose symptoms responded (reduction in a CTCAE grade) initially but who developed recurrence upon steroid taper or discontinuation. * Steroid "refractory" disease: patients whose symptoms have not clinically improved by a CTCAE grade in ≥48 hours or maximum of 14 days. * Patient may have received any number of lines of prior systemic therapy. * Patient with any solid tumor or hematologic malignancy are eligible. * Patient must not be receiving concurrent radiation therapy. * Willingness to undergo cohort-specific evaluation. * Cohort 1: Dermatologic evaluation, and skin biopsy evaluation prior to and after MTP-101-C administration. * Cohort 2: GI evaluation, and endoscopic evaluation including colonoscopies prior to and after MTP-101-C administration. * Willingness to undergo correlative blood and stool sampling. * Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2. * Patients with ECOG PS 2 wherein the decline in PS from baseline is deemed secondary to IMC may be enrolled at the discretion of Sponsor-Investigator. * Patients with ECOG PS 2 wherein PS is at baseline and deemed secondary to disease are excluded. * Have adequate organ function per specimens must be collected within 7 days prior to the start of study treatment.	* Multiple irAEs besides irCAE or IMC. * Patients with concurrent ≥Grade 3 irAEs besides irCAE or IMC that necessitate systemic immune suppression are not candidates for this trial. * Patients with irCAE and/or IMC that are not otherwise clarified in Section 5.1.5 (irCAE including alopecia etc.) are not candidates for this trial. * Patients with concomitant irAEs that are well controlled (≤Grade 1 or Grade 2 on repletion medication) may be enrolled at the discretion of Sponsor-Investigator. * Diagnosis of immunodeficiency, immunosuppression or any other form of immunosuppressive therapy besides steroids/biologics within 7 days prior to the first dose of MTP-101-C treatment. * Patients at high risk of MDRO colonization including: nursing home residence, age \>85, underlying diseases (dementia, poorly controlled diabetes, chronic wounds), in-dwelling medical devices (urinary catheters, feeding tubes, PEG tubes) and a prior history of MDRO colonization. * Contraindication to endoscopy (cohort 2 only). * Contraindication to MTP-101-C administration. * Any prior head/neck and/or abdominal surgery resulting in potentially altered absorption of orally administered FMT pills. * Active bacterial infection requiring systemic antibiotic therapy. * Received live vaccines within 30 days prior to the first dose of study treatment and while participating in the study

Inclusion Criteria

Exclusion Criteria

* Able to swallow oral medication.
* The participant provides written informed consent for the trial.
* Willingness to use contraception for duration of trial participation. Male participants: A male participant must agree to use a contraception per protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
* Receipt of high-dose systemic corticosteroids defined as 1-2mg/kg prednisone equivalent daily (either oral or intravenous) with a taper over 4-6 weeks as defined by society consensus guidelines102-105; AND
* No receipt of biologic such as but not limited to (dupilumab, rituximab) prior to enrollment.
* NOTE: Patients must have received steroids to be eligible.
* NOTE: Steroid "resistant" disease: patients whose symptoms responded (reduction in a CTCAE grade) initially but who developed recurrence upon steroid taper or discontinuation.
* NOTE: Steroid "refractory" disease: patients whose symptoms have not clinically improved by a CTCAE grade in ≥48 hours or maximum of 14 days.
* Receipt of high-dose systemic corticosteroids defined as 1-2mg/kg prednisone equivalent daily (either oral or intravenous) with a taper over 4-6 weeks as defined by society consensus guidelines102-105; AND
* No receipt of biologic such as but not limited to (TNFα inhibitor infliximab OR α₄β₇ integrin inhibitor vedolizumab) prior to enrollment.
* Patients must have received steroids to be eligible.
* Steroid "resistant" disease: patients whose symptoms responded (reduction in a CTCAE grade) initially but who developed recurrence upon steroid taper or discontinuation.
* Steroid "refractory" disease: patients whose symptoms have not clinically improved by a CTCAE grade in ≥48 hours or maximum of 14 days.
* Patient may have received any number of lines of prior systemic therapy.
* Patient with any solid tumor or hematologic malignancy are eligible.
* Patient must not be receiving concurrent radiation therapy.
* Willingness to undergo cohort-specific evaluation.
* Cohort 1: Dermatologic evaluation, and skin biopsy evaluation prior to and after MTP-101-C administration.
* Cohort 2: GI evaluation, and endoscopic evaluation including colonoscopies prior to and after MTP-101-C administration.
* Willingness to undergo correlative blood and stool sampling.
* Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2.
* Patients with ECOG PS 2 wherein the decline in PS from baseline is deemed secondary to IMC may be enrolled at the discretion of Sponsor-Investigator.
* Patients with ECOG PS 2 wherein PS is at baseline and deemed secondary to disease are excluded.
* Have adequate organ function per specimens must be collected within 7 days prior to the start of study treatment.

* Multiple irAEs besides irCAE or IMC.
* Patients with concurrent ≥Grade 3 irAEs besides irCAE or IMC that necessitate systemic immune suppression are not candidates for this trial.
* Patients with irCAE and/or IMC that are not otherwise clarified in Section 5.1.5 (irCAE including alopecia etc.) are not candidates for this trial.
* Patients with concomitant irAEs that are well controlled (≤Grade 1 or Grade 2 on repletion medication) may be enrolled at the discretion of Sponsor-Investigator.
* Diagnosis of immunodeficiency, immunosuppression or any other form of immunosuppressive therapy besides steroids/biologics within 7 days prior to the first dose of MTP-101-C treatment.
* Patients at high risk of MDRO colonization including: nursing home residence, age \>85, underlying diseases (dementia, poorly controlled diabetes, chronic wounds), in-dwelling medical devices (urinary catheters, feeding tubes, PEG tubes) and a prior history of MDRO colonization.
* Contraindication to endoscopy (cohort 2 only).
* Contraindication to MTP-101-C administration.
* Any prior head/neck and/or abdominal surgery resulting in potentially altered absorption of orally administered FMT pills.
* Active bacterial infection requiring systemic antibiotic therapy.
* Received live vaccines within 30 days prior to the first dose of study treatment and while participating in the study

Contacts and Locations

Study Contact

Danielle L Bednarz, RN

CONTACT

4126231191

bednarzdl@upmc.edu

Amy Rose, RN

CONTACT

4126478587

kennaj@upmc.edu

Principal Investigator

Diwakar M Davar, MD, PhD

PRINCIPAL_INVESTIGATOR

UPMC Hillman Cancer Center

Study Locations (Sites)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232

United States

Collaborators and Investigators

Sponsor: Diwakar Davar

Diwakar M Davar, MD, PhD, PRINCIPAL_INVESTIGATOR, UPMC Hillman Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-01-23

Study Completion Date2030-09-30

Study Record Updates

Study Start Date2025-01-23

Study Completion Date2030-09-30

Terms related to this study

Keywords Provided by Researchers

gut microbiome
anti-PD-1 therapy

Additional Relevant MeSH Terms

Immune-mediated Colitis (IMC)
Immune-related Dermatitis