Predicting Response to Immunotherapy for Melanoma With Gut Microbiome and Metabolomics (PRIMM)

This study will investigate the effects of gut microbiome diversity (richness in terms of many bacterial species in the gut) on responses and side effects of immunotherapy in advanced melanoma patients. Immunotherapy for melanoma is especially damaging for the gut with colitis which can lead to death and significant morbidity with repeated hospital admissions. The richness of the microbiome in the gut may be protective against colitis and other side effects but this needs to be confirmed. There is also some preliminary evidence that the gut microbiome diversity can enhance responses to immunotherapy in cancer but this has been shown in small numbers of melanoma patients.

Study Overview

• Status: Recruiting
• Conditions: Melanoma (Skin)

Detailed Description

This pilot project will assess the gut microbiome with metagenome sequencing before and after starting immunotherapy in stage 3 and 4 melanoma patients. The project will assess the impact of the gut microbiome on treatment response rates and side effects induced by immunotherapy.

200 stage 4 and 250 stage 3 melanoma patients naive to immunotherapy will be recruited from melanoma clinics. Stool samples will be donated pre-treatment and at follow-up visits throughout treatment. An additional sample will also be requested in the event of disease progression or toxicity necessitating treatment delay or discontinuation. An accompanying stool sample questionnaire will be completed at each sampling time point with the optional completion of a 24-hour recall food diary.

Blood samples will also be taken before and after starting immunotherapy treatment, with gastrointestinal, food frequency, quality of life questionnaires administered at baseline. An optional tumour biopsy if safe and accessible, is requested from patients in the stage 4 cohort before and after starting immunotherapy.

Microbiome data from melanoma patients will be compared with the TwinsUK healthy control gut microbiome data on more than 3000 healthy adults. This analysis will help us assess if there are major differences between the microbiome composition in the melanoma cases prior to therapy compared to the control gut microbiome data from TwinsUK.

• Study Type: Observational
• Enrollment (Anticipated): 450

Contacts and Locations

• Study Contact: Name: Clare Stockwell; Phone Number: 02071887188 (x86754); Email: clare.1.stockwell@kcl.ac.uk
• Study Contact Backup: Name: Paul Nathan; Phone Number: 0203 826 2444; Email: researchanddevelopment.enh-tr@nhs.net

Study Locations

• United Kingdom
  • London, United Kingdom
    • Recruiting
    • Guy's and St. Thomas' NHS Foundation Trust
    • Contact: Mark Harries
  • Manchester, United Kingdom
    • Recruiting
    • The Christie NHS Foundation Trust
    • Contact: Paul Lorrigan
  • Preston, United Kingdom
    • Recruiting
    • Lancashire Teaching Hospitals NHS Foundation Trust
  • Wirral, United Kingdom
    • Recruiting
    • The Clatterbridge Cancer Centre
    • Contact: Joseph Sacco
  • Middlesex
    • Northwood, Middlesex, United Kingdom, HA62RN
      • Recruiting
      • East and North Hertfordshire NHS Trust
      • Contact: Paul Nathan; Phone Number: 02038262444; Email: researchanddevelopment.enh-tr@nhs.net

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with stage 3 or 4 melanoma

Description

Inclusion Criteria:

- Patients aged over the age of 18 years with advanced melanoma due to receive first line systemic treatment with immunotherapy with a checkpoint inhibitor alone or in combination.

Exclusion Criteria:

• Patients who have had systemic anti-cancer treatment for locally advanced or metastatic disease.
• Patients unable to consent because of language barrier or inability to consent.
• Patients unable to collect or send the stool samples for geographical, social or psychological reasons.
• Persons benefitting from protection system of adults (including guardianship and curatorship)
• Pregnant or breastfeeding women

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Cohort A; Patients with stage 4 melanoma due to commence immunotherapy. Patients should be naïve to immunotherapy.
Cohort B; Patients with stage 3 melanoma who are naïve to immunotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbiome diversity via measurement of bacterial species in stool samples	Gut microbiome diversity and peripheral blood mononuclear cells immunophenotyping in relation to responses to treatment and side effects in patients with stage 3 or stage 4 melanoma receiving immunotherapy	3-5 years
Peripheral blood monocyte measurements to determine the characterisation of peripheral blood mononuclear cells (immunophenotyping) and inflammatory markers before and after starting immunotherapy treatment.	Gut microbiome diversity and peripheral blood mononuclear cells immunophenotyping in relation to responses to treatment and side effects in patients with stage 3 or stage 4 melanoma receiving immunotherapy.	3-5 years
Side effects as determined by CTCAE scale Common Toxicity Criteria for Adverse Events v5.03	Gut microbiome diversity and peripheral blood mononuclear cells immunophenotyping in relation to responses to treatment and side effects in patients with stage 3 or stage 4 melanoma receiving immunotherapy.	3-5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis of optional punch biopsy samples before and after commencing immunotherapy treatment in patients with stage 4 melanoma	Exploratory analysis to examine the association between the gut microbiome and the presence of tumour infiltrates and regulatory environments.	3-5 years

Collaborators and Investigators

• Sponsor: East and North Hertfordshire NHS Trust
• Collaborators: King's College London

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2018
• Primary Completion (Anticipated): May 2, 2023
• Study Completion (Anticipated): May 2, 2023

Study Registration Dates

• First Submitted: August 10, 2018
• First Submitted That Met QC Criteria: August 21, 2018
• First Posted (Actual): August 22, 2018

Study Record Updates

• Last Update Posted (Actual): February 27, 2020
• Last Update Submitted That Met QC Criteria: February 25, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• 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: RD2016-56

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The research results will be published in international journals and presented at scientific meetings.

Drug and device information, study documents

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