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

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ClinicalTrials.gov Identifier: NCT03643289
Recruitment Status : Recruiting
First Posted : August 22, 2018
Last Update Posted : February 27, 2020
Sponsor:
Collaborator:
King's College London
Information provided by (Responsible Party):
East and North Hertfordshire NHS Trust

Tracking Information
First Submitted Date August 10, 2018
First Posted Date August 22, 2018
Last Update Posted Date February 27, 2020
Actual Study Start Date April 4, 2018
Estimated Primary Completion Date May 2, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: February 25, 2020)
  • Gut microbiome diversity via measurement of bacterial species in stool samples [ Time Frame: 3-5 years ]
    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
  • Peripheral blood monocyte measurements to determine the characterisation of peripheral blood mononuclear cells (immunophenotyping) and inflammatory markers before and after starting immunotherapy treatment. [ Time Frame: 3-5 years ]
    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.
  • Side effects as determined by CTCAE scale Common Toxicity Criteria for Adverse Events v5.03 [ Time Frame: 3-5 years ]
    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.
Original Primary Outcome Measures
 (submitted: August 21, 2018)
  • Gut microbiome diversity via measurement of bacterial species in stool samples [ Time Frame: 5 years ]
    Gut microbiome diversity and peripheral blood mononuclear cells immunophenotyping in relation to responses to treatment and side effects in advanced melanoma patients receiving immunotherapy.
  • Peripheral blood monocyte measurements to determine the characterisation of peripheral blood mononuclear cells (immunophenotyping) and inflammatory markers before and after starting treatment. [ Time Frame: 5 years ]
    Gut microbiome diversity and peripheral blood mononuclear cells immunophenotyping in relation to responses to treatment and side effects in advanced melanoma patients receiving immunotherapy.
  • Side effects [ Time Frame: 5 years ]
    Gut microbiome diversity and peripheral blood mononuclear cells immunophenotyping in relation to responses to treatment and side effects in advanced melanoma patients receiving immunotherapy.
Change History
Current Secondary Outcome Measures
 (submitted: February 25, 2020)
Analysis of optional punch biopsy samples before and after commencing immunotherapy treatment in patients with stage 4 melanoma [ Time Frame: 3-5 years ]
Exploratory analysis to examine the association between the gut microbiome and the presence of tumour infiltrates and regulatory environments.
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Predicting Response to Immunotherapy for Melanoma With Gut Microbiome and Metabolomics
Official Title Predicting Response to Immunotherapy for Melanoma With Gut Microbiome and Metabolomics
Brief Summary 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.
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
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Stool samples, blood samples, tissue samples
Sampling Method Non-Probability Sample
Study Population Patients with stage 3 or 4 melanoma
Condition Melanoma (Skin)
Intervention Not Provided
Study Groups/Cohorts
  • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: February 25, 2020)
450
Original Estimated Enrollment
 (submitted: August 21, 2018)
160
Estimated Study Completion Date May 2, 2023
Estimated Primary Completion Date May 2, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria

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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Clare Stockwell 02071887188 (x86754) clare.1.stockwell@kcl.ac.uk
Contact: Paul Nathan 0203 826 2444 researchanddevelopment.enh-tr@nhs.net
Listed Location Countries United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number NCT03643289
Other Study ID Numbers RD2016-56
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Plan Description: The research results will be published in international journals and presented at scientific meetings.
Responsible Party East and North Hertfordshire NHS Trust
Study Sponsor East and North Hertfordshire NHS Trust
Collaborators King's College London
Investigators Not Provided
PRS Account East and North Hertfordshire NHS Trust
Verification Date February 2020