Molecular Profiling and Matched Targeted Therapy for Patients With Metastatic Melanoma

  • STATUS
    Recruiting
  • End date
    Dec 3, 2028
  • participants needed
    1000
  • sponsor
    Melanoma Institute Australia
Updated on 3 December 2021
platelet count
metastatic melanoma
cancer
BRAF
NRAS
neutrophil count
mek inhibitor
targeted therapy
trametinib
mucosal melanoma

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.

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.

Details
Condition Malignant Melanoma, Skin Cancer, Melanoma, melanoma, Metastatic Melanoma, skin cancer
Treatment Standard therapy or clinical trial, Matched targeted therapy, Matched targeted therapy, Trametinib and / or supportive care, CDK4/6 and MEK inhibitor
Clinical Study IdentifierNCT02645149
SponsorMelanoma Institute Australia
Last Modified on3 December 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Newly diagnosed and treatment nave unresectable Stage IIIB, IIIC or Stage IV melanoma (including sub types: cutaneous, mucosal, acral, ungual, uveal and unknown primary)
Archival metastatic tumour tissue available for genetic testing. Archival tissue from primary melanoma may be considered if no recent sample is available
Male or female patients aged 18 or over
Written informed consent for molecular genetic testing of tumour tissue (for both standard and research tests)
Inclusion Criteria for Matched Targeted Therapy
\. Received available standard therapies for metastatic melanoma and
progressed, unable to tolerate standard therapy, or standard therapy
contraindicated
\. Written informed consent to receive targeted therapy (if applicable) and
clinical follow up
\. Patient has an 'actionable' genetic aberration and matched targeted
therapy is available. Patients with no genetic aberration or where no matched
targeted therapy is available, patients will be offered trametinib 9. ECOG
status 0 - 2. 10. Adequate haematological, hepatic and renal organ function as
defined by
White cell count 2.0 109/L
Neutrophil count 1.5 109/L
Haemoglobin 90 g/L
Platelet count 100 x 109/L
Total bilirubin 3.0 x ULN
Alanine transaminase 3.0 x ULN
Aspartate aminotransferase 3.0 x ULN
Serum creatinine 1.5 x the upper limit of normal (ULN). 11. Life expectancy > 30 days. 12. Women of child bearing potential (WOCBP) to use contraception to avoid pregnancy
Non sterile men with female partners of CBP to use contraception to avoid pregnancy
Drug specific inclusions

Exclusion Criteria

An expectation for the need for concurrent radiotherapy (unless safety has been established with the matched drug regimen and is directed at one anatomical region for symptom control)
Any investigational drug or other systemic drug therapy for melanoma within 14 days or 5 half-lives from baseline, whichever is shorter
Pregnant or breast feeding females
Drug specific exclusions
Any clinically significant gastrointestinal abnormalities which may impair intake or absorption of the study drug
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note