Clinical trial NCT03643289: Predicting Response to Immunotherapy for Melanoma With Gut Microbiome and Metabolomics
Official title: Predicting Response to Immunotherapy for Melanoma With Gut Microbiome and Metabolomics
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Melanoma (Skin)
Lead sponsor: East and North Hertfordshire NHS Trust
Sponsor class: OTHER_GOV
Collaborators: name: King's College London
First posted: 2018-08-22
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with stage 3 or 4 melanoma

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.

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

Primary outcomes:
measure: Gut microbiome diversity via measurement of bacterial species in stool samples
timeFrame: 3-5 years
measure: Peripheral blood monocyte measurements to determine the characterisation of peripheral blood mononuclear cells (immunophenotyping) and inflammatory markers before and after starting immunotherapy treatment.
timeFrame: 3-5 years
measure: Side effects as determined by CTCAE scale Common Toxicity Criteria for Adverse Events v5.03
timeFrame: 3-5 years
Secondary outcomes:
measure: Analysis of optional punch biopsy samples before and after commencing immunotherapy treatment in patients with stage 4 melanoma
timeFrame: 3-5 years
Other outcomes:
Locations:
city: Northwood
country: United Kingdom
facility: East and North Hertfordshire NHS Trust
state: Middlesex
city: London
country: United Kingdom
facility: Guy's and St. Thomas' NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Preston
country: United Kingdom
facility: Lancashire Teaching Hospitals NHS Foundation Trust
city: Wirral
country: United Kingdom
facility: The Clatterbridge Cancer Centre
Study officials:
References: