Targeted therapy for patients with advanced melanoma based on genetic profiling

Molecular Profiling and Matched Targeted Therapy for Patients With Metastatic Melanoma

This study is testing whether personalized treatments based on the genetic makeup of tumors can help patients with advanced melanoma who haven't responded to standard therapies.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 1000 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: Melanoma Institute Australia (other)
• Drugs / interventions: trametinib, immunotherapy
• Locations: 2 sites (Westmead, New South Wales and 1 other locations)
• Trial ID: NCT02645149 on ClinicalTrials.gov

What this trial studies

This clinical trial focuses on patients with unresectable Stage III or IV metastatic melanoma who have not responded to or cannot receive standard therapies. Participants will undergo genetic profiling of their tumor tissue to identify specific mutations, allowing for the assignment of targeted therapies that match these mutations. The study aims to improve treatment outcomes by utilizing a comprehensive gene testing platform that examines a wide range of cancer-related genes. Patients with wild-type BRAF and NRAS genes will receive standard care before being considered for further targeted therapies based on their genetic profile.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and over with newly diagnosed unresectable Stage III or IV melanoma and available tumor tissue for genetic testing.

Not a fit: Patients who have already received standard therapies for metastatic melanoma and do not have actionable genetic aberrations may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to more effective and personalized treatment options for patients with advanced melanoma.

How similar studies have performed: Other studies have shown promise in using targeted therapies based on genetic profiling in various cancers, indicating a potential for success in this novel approach for melanoma.

Eligibility 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

Where this trial is running

Westmead, New South Wales and 1 other locations

• Westmead Hospital — Westmead, New South Wales, Australia (NOT_YET_RECRUITING)
• Melanoma Institute Australia — Wollstonecraft, New South Wales, Australia (RECRUITING)

Study contacts

• Study coordinator: Monica Osorio

Conditions: Melanoma, Metastatic Melanoma, Molecular Testing, Targeted Therapy