Molecular Profiling and Matched Targeted Therapy for Patients With Metastatic Melanoma (MatchMel)
Melanoma
About this trial
This is an interventional treatment trial for Melanoma focused on measuring Metastatic Melanoma, Molecular Testing, Targeted Therapy
Eligibility 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 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:
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.
Exclusion criteria for Matched Targeted Therapy:
- 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
Sites / Locations
- Westmead Hospital
- Melanoma Institute AustraliaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Experimental
Experimental
Experimental
Experimental
Experimental
Other
A1. Non-V600 BRAF, BRAF wildtype, NRAS wildtype. Actionable gene mutation, matched drug available
A2. Non-V600 BRAF, BRAF wildtype, NRAS wildtype. Actionable gene mutation, no matched drug available
A3. Non-V600 BRAF, BRAF wild type and NRAS wild type melanoma - no actionable genetic aberration
B. Mucosal melanoma
C. NRAS mutant melanoma
D. BRAF V600 mutant melanoma
Patients will receive targeted drug matched to the actionable gene mutation detected on NGS testing. 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 trametinib, or clinical trials if available.
Patients may have an actionable aberration for which there is no current study-specific drug supply available. In this scenario, access will be sought for compassionate use of the relevant approved targeted therapy.
Patients for whom there is no actionable genetic aberration will receive trametinib, based upon the known MAPK excess activity in the majority of melanomas that may be inhibited by a MEK inhibitor
Patients will receive combined trametinib and ribociclib based on evidence to suggest that combined MEK inhibition and CDK4/6 inhibition may be effective. After failure of trametinib and ribociclib, actionable genetic aberrations from the NGS testing will be reviewed for the opportunity to use a further targeted therapy off label.
Patients with an NRAS mutation detected on standard gene testing only will receive combined trametinib and ribociclib based on evidence that combining MEK inhibition and CDK4/6 inhibition is a viable treatment option.
Patients will receive standard of care treatment only.