Melanoma (Skin)PRIMMNCT03643289
Predicting Response to Immunotherapy for Melanoma With Gut Microbiome and Metabolomics
An observational study of Melanoma (Skin), run by East and North Hertfordshire NHS Trust at 5 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma (Skin)
- How many people
- 450 participants
- Where
- 5 sitesUnited Kingdom
- Study dates
- 4 Apr 2018to 2 May 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with stage 3 or 4 melanoma
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United Kingdom5 sites, 5 recruiting
- Recruiting
Guy's and St. Thomas' NHS Foundation Trust
London
Mark Harries
- Recruiting
The Christie NHS Foundation Trust
Manchester
Paul Lorrigan
- Recruiting
The Clatterbridge Cancer Centre
Metropolitan Borough of Wirral
Joseph Sacco
- Recruiting
East and North Hertfordshire NHS Trust
Northwood, Middlesex, HA62RN
Paul Nathan, 02038262444, researchanddevelopment.enh-tr@nhs.net
- Recruiting
Lancashire Teaching Hospitals NHS Foundation Trust
Preston
Ruth Board
About this study
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.
Read the 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.
- Conditions
- Melanoma (Skin)
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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.
Measured: 3-5 years
Secondary outcomes (1)
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.
Measured: 3-5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2018
- Study start4 Apr 2018
- Primary completion2 May 2023 (estimated)
- Study completion2 May 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Melanoma (Skin)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 450 participants (estimated)
Sponsor and investigators
- Lead sponsor
- East and North Hertfordshire NHS Trust
- Sponsor type
- Other government
- Collaborators
- King's College London
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03643289
- Sponsor's protocol ID
- RD2016-56
- Acronym
- PRIMM
- Status last verified
- Feb 2020
- First submitted
- 10 Aug 2018
- Last updated
- 27 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The research results will be published in international journals and presented at scientific meetings.
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Predicting Response to Immunotherapy for Melanoma With Gut Microbiome and Metabolomics
- ClinicalTrials.gov ID
- NCT03643289
- Acronym / sponsor ID
- PRIMM / RD2016-56
- Conditions
- Melanoma (Skin)
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 450 participants (estimated)
- Lead sponsor
- East and North Hertfordshire NHS TrustOther government
- Collaborators
- King's College London
- Study start
- 4 Apr 2018 (actual)
- Primary completion
- 2 May 2023 (estimated)
- Study completion
- 2 May 2023 (estimated)
- First posted
- 22 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with stage 3 or 4 melanoma
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
1 secondary outcome
Analysis of optional punch biopsy samples before and after commencing immunotherapy treatment in patients with stage 4 melanoma
Time frame: 3-5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2020.
- Individual participant dataSharing planned: No. The research results will be published in international journals and presented at scientific meetings.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Melanoma (Skin), run by East and North Hertfordshire NHS Trust at 5 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Clare Stockwell (02071887188 (x86754), clare.1.stockwell@kcl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gut microbiome diversity via measurement of bacterial species in stool samples (time frame: 3-5 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2020.