Molecular Profiling and Matched Targeted Therapy for Patients With Metastatic Melanoma (MatchMel)
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|ClinicalTrials.gov Identifier: NCT02645149|
Recruitment Status : Not yet recruiting
First Posted : January 1, 2016
Last Update Posted : November 9, 2017
This is a patient oriented translational research project aiming to improve clinical outcomes for patients with BRAF and NRAS wild-type unresectable Stage III or Stage IV metastatic melanoma who have progressed on, or are unable to receive standard therapy (in general, immunotherapy). Consecutive patients seen at three major clinics and fitting the broad eligibility criteria will be invited to participate.
The approach is designed to test the impact of different targeted drugs on different mutations in a single type of cancer. In this project, patients will have tumour tissue genetically profiled to determine which mutation(s) are present, and will then be assigned to receive a matched drug expected to target the mutation(s) in the tumour. Where multiple targets are identified in one patient, or where multiple potential therapies would be appropriate for a single tumour mutation, the treating clinician may determine the appropriate therapeutic approach after consultation with the study team, using the latest version of library of matched therapies.
|Condition or disease||Intervention/treatment||Phase|
|Melanoma||Drug: Standard therapy or clinical trial Drug: Matched targeted therapy Drug: Trametinib and / or supportive care||Phase 4|
Current standard of care testing covers mutations in the BRAF and NRAS genes. The comprehensive gene testing platform to be used in this project is designed to interrogate the entire coding sequence of 315 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer. These genes are known to be somatically altered in solid cancers based on recent scientific and clinical literature. The test panel will be used on melanoma tissue from patients pre-screened as having BRAF and NRAS wild-type melanoma. The extent of testing will be updated to reflect new discoveries in melanoma tumourigenesis and availability of new therapies as the project proceeds. Testing will be performed on formalin-fixed and paraffin-embedded samples of metastatic tissue. Archival tissue from primary or regional recurrent melanoma may be considered if no recent sample is available or possible.
All new patients with unresectable Stage III or IV melanoma seen at each participating site will be invited to participate. Following written consent, all patients will undergo the standard testing for BRAF and NRAS mutations. Patients found to have mutations in either gene will receive standard treatment with dabrafenib and / or trametinib and no further molecular testing.
Patients with wild type versions of BRAF and NRAS genes will have tumour tissue sent for the extended gene testing platform. These patients will first receive standard of care therapy for wild type BRAF / NRAS melanoma, where possible. Once standard therapies have been exhausted (because of disease progression or intolerable adverse events), patients will then receive a targeted therapy matched for their genetic result, if applicable. The selection of targeted therapy will be based on clinical evidence of activity in other solid tumours harbouring similar mutations and / or in at least Phase I testing in melanoma. The table of matched therapies will be modified and extended as new findings from clinical research become available. Patients may be included in specific clinical trials of targeted therapies if available, e.g. a MEK inhibitor combined with an MDM2 inhibitor (AMG232) for BRAF and TP53 wild-type melanoma or a MEK inhibitor combined with a CDK4/6 inhibitor for BRAF wild-type melanoma.
The extensive molecular profiling platform is fully validated and will be conducted by an external provider accredited by an authority with the responsibility to award Laboratory Accreditation at private and public facilities.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||1000 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Molecular Profiling and Matched Targeted Therapy for Patients With Metastatic Melanoma|
|Anticipated Study Start Date :||February 2018|
|Estimated Primary Completion Date :||June 2021|
|Estimated Study Completion Date :||June 2021|
Standard therapy or clinical trial
Patients with BRAF and NRAS wild type tumour for whom there is no actionable genetic aberration in tumour tissue. These patients will receive trametinib based upon the known MAPK excess activity in the majority of melanomas that may be inhibited by a MEK inhibitor.
Drug: Standard therapy or clinical trial
Patients with BRAF V600 and NRAS mutations detected by standard of care tumour testing will be treated with standard approved therapies or on clinical trials.
Matched targeted therapy
Patients with BRAF and NRAS wild type tumour for whom there is a targeted therapy available, will receive targeted drug matched to gene defect in tumour. If a patient cannot receive the matched targeted therapy because of the existence of one or more drug specific exclusion criteria, an alternative matched therapy may be assigned, or these patients will be treated per standard therapy / clinical trial arm.
Drug: Matched targeted therapy
Patients with tumour found to be BRAF and NRAS wild type will have tumour tested further using the extended molecular testing platform designed for this project. Patients will first receive standard therapy(ies) for BRAF / NRAS wild type melanoma until disease progression or intolerable drug toxicities. Followed by a targeted therapy matched to the genetic aberration detected in their tumour as listed above.
Trametinib and / or supportive care
Patients with BRAF V600 and NRAS mutations will be treated with standard approved therapies or on clinical trials, and will be followed for clinical response and survival outcomes.
Drug: Trametinib and / or supportive care
Patients with BRAF and NRAS wild type tumour for whom there is no actionable genetic aberration in tumour tissue following extended molecular testing, may receive trametinib (if not already administered as part of standard care) and/or supportive care.
- Type and frequency of genetic aberrations in BRAF/NRAS wild-type metastatic melanoma [ Time Frame: For the duration of the study, estimated at 5 years. ]Genetic aberrations detected by extended molecular profiling in patients with BRAF / NRAS wild type metastatic melanoma.
- Proportion of patients with BRAS/NRAS wild-type melanoma receiving targeted therapy [ Time Frame: For the duration of the study, estimated at 5 years. ]Patients able to receive matched targeted therapy as a result of genetic aberrations detected with extended molecular profiling, from a pool of all BRAF / NRAS wild type patients.
- Proportion of patients who have BRAF/NRAS wild type melanoma [ Time Frame: For the duration of the study, estimated at 5 years. ]From consecutive patients with metastatic melanoma tested for common BRAF / NRAS mutations as part of standard care.
- Proportion of patients with complete (CR) or partial (PR) response. [ Time Frame: From date of targeted therapy commencement until the date of first documented objective partial or complete response per RECIST, assessed up to 60 months. ]Proportion of patients who received matched targeted therapy as a result of genetic aberrations detected with extended molecular profiling who had a complete (CR) or partial (PR) response.
- Duration of response [ Time Frame: From date of first objective partial or complete response to disease progression or death, which ever is sooner, assessed up to 60 months. ]For patients experiencing a complete or partial response to study treatment, the amount of time from this outcome to the time that disease progression or death occurs
- Progression free survival [ Time Frame: From date of targeted therapy commencement to date of objective disease progression per RECIST, assessed up to 60 months. ]The period of time from study entry to progression of disease or death
- Overall survival [ Time Frame: From date of targeted therapy commencement to date of death from any cause, assessed up to 60 months. ]The proportion of patients alive from the time of study entry
- Correlation of genetic aberration detected in tumour tissue with clinical response and disease progression [ Time Frame: From date of targeted therapy commencement to date of to partial or complete response or disease progression, assessed up to 60 months. ]Identify genetic predictors of response and progression using the extended molecular testing platform.
- Correlation of with genetic aberration detected in tumour tissue with age at diagnosis, site of primary tumour, chronic sun damaged skin. [ Time Frame: At baseline ]Identify clinicopathological correlates (e.g. age at diagnosis, site of primary tumour, chronic sun damaged skin etc.) of molecular subtypes of melanoma at baseline.
- Correlation of genetic aberration detected in tumour tissue with site of metastases, nodular or superficial spreading disease. [ Time Frame: At baseline ]Identify the differences in disease behaviour (e.g. site of metastases, nodular or superficial spreading disease) based on molecular subtypes of melanoma.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02645149
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02645149
|Contact: Maria Gonzalez||612 9911 firstname.lastname@example.org|
|Australia, New South Wales|
|Royal Prince Alfred Hospital||Not yet recruiting|
|Camperdown, New South Wales, Australia, 2050|
|Contact: Maria Gonzalez 612 9911 7200 email@example.com|
|Principal Investigator: John Thompson|
|Westmead, New South Wales, Australia, 2145|
|Melanoma Institute Australia||Not yet recruiting|
|Wollstonecraft, New South Wales, Australia, 2065|
|Contact: Maria Gonzalez +612 9911 7200 firstname.lastname@example.org|
|Contact: Alex Menzies +612 9911 7200 email@example.com|
|Sub-Investigator: Georgina Long|
|Principal Investigator: Alex Menzies|
|Study Chair:||Alex Menzies||Melanoma Institute Australia|