None listed
Conditions
Brief summary
The primary purpose of this study is to evaluate the efficacy of cancer therapy which is matched specifically to the genetic profile of each individual's tumour in patients with metastatic melanoma. Who is it for? You may be eligible to participate in this study if you are aged 18 or over, and are newly diagnosed with stage IIIB, IIIC or IV melanoma. Study details: All participants in this study will first undergo standard testing to establish whether a certain type of genetic mutation (BRAF/NRAS mutation) is present in their tumour cells. This is carried out using an existing or fresh tumour tissue sample. All participants will then begin standard care therapy for the melanoma. In participants with tumours testing negative for BRAF/NRAS mutations in the initial test, and who show disease progression or who are unable to continue standard care therapy, further testing on their tumour tissue sample will be carried out. This will provide further information regarding the genetic profile of the tumour. Researchers will then match this genetic profile to a specific therapy which targets it. Researchers will measure disease progression and survival to evaluate the efficacy of the matched targeted treatment in comparison to standard care only. The matched targeted therapies which may be used will be continuously updated as other research provides more information on which drugs may target which genetic profiles. It is hoped that the findings of this study will provide valuable information regarding the efficacy of therapies which target the specific genetic profile of metastatic melanoma tumours, in comparison to the current standard care.
Interventions
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 with unresectable Stage III or IV melanoma will be invited to participate. All patients are first provided with the standard care BRAF/NRAS mutation testing, foll
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 with unresectable Stage III or IV melanoma will be invited to participate. All patients are first provided with the standard care BRAF/NRAS mutation testing, followed by standard care therapy. Those patients with melanoma found to be BRAF/NRAS wild type will also undergo extended molecular testing of their melanoma. The extended test in this project covers approximately 400 cancer related genes. Following progression on standard therapy, patients with BRAF/NRAS wild type melanoma will be reviewed at a meeting of the project multidisciplinary team. Patients will be offered a targeted therapy matched to the genetic aberrations detected on extended testing. The current library of targeted therapies include: Everolimus Bortezomib Cabozantinib Ceritinib Crizotinib Dasatinib Erlotinib Everolimus Gefitinib Imatinib Lapatinib Nilotinib Olaparib Palbociclib Pazopanib Ramucirumab Regorafenib Sorafenib Sunitinib Trametinib Vorinostat Where multiple targets are identified in one patient, or where multiple potential therapies would be appropriate for a single tumour mutation, the appropriate therapeutic approach will be decided after consultation with the multidisciplinary team, using the latest version of library of matched therapies. Similarly, for patients where no genetic aberration was detected or for whom there is no current targeted therapy available for a specific genetic aberration, further treatment will be discussed with the molecular multidisciplinary team formed for this project. All patients who consent to participate in the study will be followed up until death.
Sponsors
Melanoma Institute Australia
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
INITIAL INCLUSION CRITERIA: Newly diagnosed and treatment naive unresectable Stage IIIB, IIIC or Stage IV melanoma. Archival or fresh 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 EXTENDED MOLECULAR TESTING: Standard of care molecular tumour testing which has identified BRAF / NRAS wild type tumour tissue. 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. ECOG status 0 - 2. Adequate haematological, hepatic and renal organ function as defined by: White cell count = or > 2.0 × 10^9/L Neutrophil count = or > 1.5 × 10^9/L Haemoglobin = or > 90 g/L Platelet count = or >100 x 10^9/L Total bilirubin < or = 3.0 x ULN Alanine transaminase < or = 3.0 x ULN Aspartate aminotransferase < or = 3.0 x ULN Serum creatinine < or = 1.5 x the upper limit of normal (ULN). Life expectancy > 30 days. 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 (refer to the regulatory approved drug specific Product Information provided)
Exclusion criteria
EXCLUSION CRITERIA FOR MATCHED TARGETED THERAPY: An expectation for the need for concurrent radiotherapy (unless safety has been established with the matched drug regimen). 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 (refer to the regulatory approved drug specific Product Information Sheet provided)
Outcome results
None listed