A Pilot Study of Trientine With Vemurafenib for the Treatment BRAF Mutated Metastatic Melanoma
The purpose of this study is to evaluate the safety of combination therapy with vemurafenib and trientine in patients with BRAF mutated metastatic melanoma.
Vemurafenib is a drug that is currently approved by the United States Food and Drug Administration (FDA) and by the European Medicines Agency (EMA) to treat adult patients with melanoma that has spread to other parts of the body or cannot be removed by surgery. It can only be used in patients whose cancer has a change (mutation) in the "BRAF" gene.
Preclinical data suggests that use of a copper chelator (reducer) is a strategy to block cellular signaling activity which would result in anti-tumor effects (slow tumor growth). Trientine is a copper chelator and is FDA approved for the treatment of Wilson's disease (a disease of copper metabolism) and is generally well tolerated. It works by binding to copper to help remove it from the body. Trientine is not FDA approved for the treatment of melanoma and its use in this study is investigational. "Investigational" means the study drug is still being tested in research studies.
All patients will receive vemurafenib at 960mg PO twice daily with continuous dosing in combination with trientine in escalating doses. The dose of trientine will depend on what portion of the study.
In order to participate in the study, patients must test positive for the change (mutation) in the BRAF gene.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study of Trientine With Vemurafenib for the Treatment BRAF Mutated Metastatic Melanoma|
- Maximum Tolerated Dose [ Time Frame: 1 Cycle (4 Weeks) ] [ Designated as safety issue: Yes ]Maximum Tolerated Dose is defined as the highest dose level in which ≤1 of 6 patients experience a dose limiting toxicity.
- Overall Response [ Time Frame: 1 year ] [ Designated as safety issue: No ]The number of complete and partial responses using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee v 1.1
- Progression Free Survival (PFS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]PFS is defined as the time from study enrollment to disease progression or death due to any cause, whichever comes first.
- Overall Survival (OS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]OS is defined from enrollment to death due to any cause.
- The change in phosphorylated Erk kinase activity relative to total Erk kinase activity [ Time Frame: Pre-treatment; two weeks into combination therapy (day 15), and at the time of disease progression while still on combination therapy, up to 2 years ] [ Designated as safety issue: No ]
- The change in phosphorylated MEK kinase activity relative to total MEK kinase activity [ Time Frame: Pre-treatment; two weeks into combination therapy (day 15), and at the time of disease progression while still on combination therapy, up to 2 years ] [ Designated as safety issue: No ]
- The change in the expression of the copper transporter CTR1 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Change will be measured as the percent change compared to the baseline status
- Incidence of hyperproliferative skin lesions, specifically cutaneous squamous cell carcinomas and keratoacanthomas [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||April 2014|
|Estimated Primary Completion Date:||January 2017 (Final data collection date for primary outcome measure)|
Please refer to this study by its ClinicalTrials.gov identifier: NCT02068079
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||April K Salama, MD||Duke University|