Fecal Microbiota Transplantation (FMT) in Metastatic Melanoma Patients Who Failed Immunotherapy

Altering the Gut Microbiota of Melanoma Patients Who Failed Immunotherapy Using Fecal Microbiota Transplantation (FMT) From Responding Patients

Altering the Gut Microbiota of Melanoma Patients Who Failed Immunotherapy Using Fecal Microbiota Transplantation (FMT) From Responding Patients.

FMT includes both colonoscopy and stool capsules.

Study Overview

• Status: Unknown
• Conditions: Melanoma Stage Iv; Unresectable Stage III Melanoma
• Intervention / Treatment: Procedure: Fecal Microbiota Transplant (FMT)

Detailed Description

This is a phase I single-center study of fecal microbiota transplant (FMT) in melanoma patients who failed at least one line of PD-1 blockade.

Eligible patients must have a disease amenable to biopsy and lack of contra-indications to FMT.

Patients will undergo a baseline evaluation including imaging, tumor biopsy, blood samples and stool studies to confirm suitability for the study.

Eligible patients will undergo FMT. The FMT includes a colonoscopy followed by stool capsules.

Patients will undergo repeated evaluations including follow-up blood, stool and radiological testings.

The study will be conducted over a 24-week period.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Israel
  • Tel HaShomer, Israel, 5262620
    • Recruiting
    • Sheba Medical Center
    • Contact: Erez N Baruch, MD; Phone Number: +972.530.4591; Email: Erez.Baruch@sheba.health.gov.il
    • Contact: Ben S Boursi, MD; Phone Number: +972.530.2542; Email: Ben.Boursi@sheba.health.gov.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A histologically confirmed diagnosis of metastatic melanoma.
• Failed at least one line of PD-1 blockade.
• ECOG Performance Status 0-2
• Able to provide written informed consent.

Exclusion Criteria:

• Presence of absolute contra-indications to FMT administration.
• Severe dietary allergies (e.g. shellfish, nuts, seafood).
• Anatomic contra-indications to colonoscopy.
• Inability to swallow capsules.
• Current participation in a study of an investigational agent.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (> 10 mg prednisone daily or equivalent) or any other form of immunosuppressive therapy prior to trial treatment.
• History of bleeding disorder, chronic kidney disease, Inflammatory bowel disease.
• History of a major abdominal surgery
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Fecal Microbiota Transplant (FMT); FMT includes a colonoscopy conducted by a gastroenterologist followed by stool capsules which will be swallowed by the patient.

Procedure: Fecal Microbiota Transplant (FMT); Patients with metastatic melanoma who responded to immunotherapy will serve as the fecal implant donors. The tested fecal implant will be used for two different products. The first part of the tested stool will be mixed with a saline solution, strained and infused into your bowel using colonoscopy. The second part of the tested stool will be packed into capsules. These stool capsules are at the size of standard drug-containing capsules and can be swallowed in a standard manner. Stool capsules are a common method of FMT and has been used worldwide for several years. After the colonoscopy, you will be asked to swallow the capsules. Swallowing the capsules will be conducted at the clinic, and does not require any additional procedures.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of FMT-related Adverse Events	Number of patients with adverse events that emerged post FMT	4 years
Proper implant engraftment	Comparing of the patients' gut bacterial composition pre and post-FMT and in relation to their donors. Bacterial composition will be quantified by the operational taxonomic unit (OTU) in the stool	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in composition of immune cell population	Changes in the relative abundance of different immune cell population (such as the proportion of CD8+ T cells) pre and post-FMT.	4 years
Changes in activity of immune cells	Changes in levels of proteins that represent immune activity against cancer (such as measurements of blood interferon gamma levels), pre and post FMT	4 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Number of patients with objective responses divided by the total number of evaluable patients, according to imaging studies (RECIST 1.1) and iRECIST.	4 years

Collaborators and Investigators

• Sponsor: Sheba Medical Center
• Investigators: Principal Investigator: Gal Markel, MD, PhD, Sheba Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 30, 2017
• Primary Completion (ANTICIPATED): December 30, 2019
• Study Completion (ANTICIPATED): December 30, 2021

Study Registration Dates

• First Submitted: November 20, 2017
• First Submitted That Met QC Criteria: November 22, 2017
• First Posted (ACTUAL): November 27, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 3, 2019
• Last Update Submitted That Met QC Criteria: April 2, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Fecal Microbiota Transplantation; Immunotherapy; Melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: SHEBA-17-3956-GM-CTIL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No