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 melanomaa type of cancer that develops from melanocytes, which are the cells that produce pigment generally in the skin (but can develop in other areas of the body) who have progressed on, or are unable to receive standard therapy (in general, immunotherapya treatment that uses a person's immune system to fight cancer). 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 cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs. In this project, patients will have tumoura tissue mass that forms from groups of unhealthy cells tissuea group of cells that work together to perform a function 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.
Intervention / Treatment
- Drug: Standard therapy or clinical trial
- Drug: Matched targeted therapymedication that targets specific molecular features of cancer cells
- Drug: Trametinib and / or supportive care
- Drug: CDK4/6 and MEK inhibitor
- Drug: Compassionate Access Targeted Therapy
Inclusion Criteria
Inclusion criteria for Inclusion in Molecular Testing Platform:
- Newly diagnosed and treatment naïve 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 testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success. Archival tissue from primary melanoma may be considered if no recent sample is available.
- Male or female patients aged 18 or over.
- Written informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment. for molecular genetic testing of tumour tissue (for both standard and research tests).
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. 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.13. Non sterile men with female partners of CBP to use contraception to avoid pregnancy.
14. Drug specific inclusions.