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Trial record 41 of 2208 for:    Melanoma

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 : May 3, 2018
Sponsor:
Information provided by (Responsible Party):
Melanoma Institute Australia

Brief Summary:

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

Detailed Description:

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Molecular Profiling and Matched Targeted Therapy for Patients With Metastatic Melanoma
Estimated Study Start Date : August 2018
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : August 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma
Drug Information available for: Trametinib

Arm Intervention/treatment
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.
Other Names:
  • Chemotherapy
  • Immunotherapy
  • Biological agent

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.
Other Names:
  • AKT gene - Everolimus
  • ALK - Ceritinib or Crizotinib
  • ATM - Olaparib
  • BRAF fusion - Trametinib
  • BRCA1 - Olaparib
  • BRCA2 - Olaparib
  • CCND1 - Palbociclib
  • CCND3 - Palbociclib
  • CDK4 - Palbociclib
  • CDKN2A - Palbociclib
  • EGFR - Erlotinib, Gefitinib or Lapatinib
  • ERBB2 - Lapatinib
  • ERBB3 - Lapatinib
  • ERBB4 - Lapatinib
  • FBXW7 - Everolimus
  • FGF/R - Sorafenib
  • GNA11 - Sorafenib or Trametinib
  • GNAQ - Sorafenib or Trametinib
  • HGF - Cabozantinib
  • HGF - Crizotinib
  • HRAS - Sorafenib or Trametinib
  • IDH1 - Vorinostat
  • KDR - Cabozantinib or Ramucirumab
  • KIT - Dasatinib, Imatinib, Nilotinib, Pazopanib, Regorafenib, Sorafenib or Sunitinib
  • KRAS - Sorafenib or Trametinib
  • MAP2K1 - Palbociclib or Trametinib
  • MET - Crizotinib
  • mTOR - Everolimus
  • NF1 - Everolimus, Sorafenib or Trametinib
  • PDGFR - Imatinib
  • PIK3CA - Everolimus
  • PTEN - Everolimus
  • RICTOR - Everolimus
  • STK11 - Everolimus
  • TP53 - Bortezomib or Palbociclib

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.
Other Names:
  • Trametinib
  • Supportive care




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria for Inclusion in Molecular Testing Platform:

  1. Newly diagnosed and treatment naïve unresectable Stage IIIB, IIIC or Stage IV melanoma.
  2. Archival metastatic tumour tissue available for genetic testing. Archival tissue from primary melanoma may be considered if no recent sample is available.
  3. Male or female patients aged 18 or over.
  4. Written informed consent for molecular genetic testing of tumour tissue (for both standard and research tests).
  5. Standard of care molecular tumour testing which has identified BRAF / NRAS wild type tumour tissue.

    Inclusion Criteria for Matched Targeted Therapy:

  6. Received available standard therapies for metastatic melanoma and progressed, unable to tolerate standard therapy, or standard therapy contraindicated.
  7. Written informed consent to receive targeted therapy (if applicable) and clinical follow up.
  8. ECOG status 0 - 2.
  9. Adequate haematological, hepatic and renal organ function as defined by:

    1. White cell count ≥ 2.0 × 109/L
    2. Neutrophil count ≥ 1.5 × 109/L
    3. Haemoglobin ≥ 90 g/L
    4. Platelet count ≥ 100 x 109/L
    5. Total bilirubin ≤ 3.0 x ULN
    6. Alanine transaminase ≤ 3.0 x ULN
    7. Aspartate aminotransferase ≤ 3.0 x ULN
    8. Serum creatinine ≤ 1.5 x the upper limit of normal (ULN).
  10. Life expectancy > 30 days.
  11. Women of child bearing potential (WOCBP) to use contraception to avoid pregnancy.
  12. Non sterile men with female partners of CBP to use contraception to avoid pregnancy.
  13. Drug specific inclusions.

Exclusion criteria for Matched Targeted Therapy:

  1. An expectation for the need for concurrent radiotherapy (unless safety has been established with the matched drug regimen).
  2. Any investigational drug or other systemic drug therapy for melanoma within 14 days or 5 half-lives from baseline, whichever is shorter.
  3. Pregnant or breast feeding females.
  4. Drug specific exclusions.

Information from the National Library of Medicine

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


Contacts
Contact: Maria Gonzalez 612 9911 7200 maria.gonzalez@melanoma.org.au

Locations
Australia, New South Wales
Royal Prince Alfred Hospital Not yet recruiting
Camperdown, New South Wales, Australia, 2050
Contact: Maria Gonzalez    612 9911 7200    maria.gonzalez@melanoma.org.au   
Principal Investigator: John Thompson         
Westmead Hospital
Westmead, New South Wales, Australia, 2145
Melanoma Institute Australia Not yet recruiting
Wollstonecraft, New South Wales, Australia, 2065
Contact: Maria Gonzalez    +612 9911 7200    maria.gonzalez@melanoma.org.au   
Contact: Alex Menzies    +612 9911 7200    info@melanoma.org.au   
Sub-Investigator: Georgina Long         
Principal Investigator: Alex Menzies         
Sponsors and Collaborators
Melanoma Institute Australia
Investigators
Study Chair: Alex Menzies Melanoma Institute Australia

Responsible Party: Melanoma Institute Australia
ClinicalTrials.gov Identifier: NCT02645149     History of Changes
Other Study ID Numbers: MIA2015/174
First Posted: January 1, 2016    Key Record Dates
Last Update Posted: May 3, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Melanoma Institute Australia:
Metastatic Melanoma
Molecular Testing
Targeted Therapy

Additional relevant MeSH terms:
Melanoma
Nevi and Melanomas
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Sorafenib
Lapatinib
Olaparib
Palbociclib
Trametinib
Everolimus
Sirolimus
Imatinib Mesylate
Crizotinib
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Poly(ADP-ribose) Polymerase Inhibitors