Molecular Profiling and Matched Targeted Therapy for Patients With Metastatic Melanoma

• Status: Not yet recruiting
• Trial end date: 2028-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Melanoma Institute Australia
• Collaborator: Novartis
• Treatments: Ceritinib; Crizotinib; Everolimus; Imatinib Mesylate; Lapatinib; Olaparib; Palbociclib; Sirolimus; Sorafenib; Trametinib

Criteria

Inclusion criteria for Inclusion in Molecular Testing Platform:

1. Newly diagnosed and treatment naïve unresectable Stage IIIB, IIIC or Stage IV melanoma (including sub types: cutaneous, mucosal, acral, ungual, uveal and unknown primary).

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).

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:

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). 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:

1. 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).

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.

5. Any clinically significant gastrointestinal abnormalities which may impair intake or absorption of the study drug