A Pilot Study of Trientine With Vemurafenib for the Treatment BRAF Mutated Metastatic Melanoma

Phase 1

Withdrawn

• Conditions: Melanoma
• Interventions: Drug: Vemurafenib and Trientine

• Registration Number: NCT02068079
• Lead Sponsor: Duke University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-02-19
• Study First Submitted QC: 2014-02-19
• Study First Posted: 2014-02-20
• Study Start: 2014-04
• Primary Completion: 2015-11
• Study Completion: 2015-11
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-28
• Last Update Posted: 2019-01-30

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Vemurafenib and Trientine	Vemurafenib and Trientine	-

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose	1 Cycle (4 Weeks)	Maximum Tolerated Dose is defined as the highest dose level in which ≤1 of 6 patients experience a dose limiting toxicity.

Secondary Outcome Measures

Name	Time	Method
Overall Response	1 year	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)	2 years	PFS is defined as the time from study enrollment to disease progression or death due to any cause, whichever comes first.
Overall Survival (OS)	2 years	OS is defined from enrollment to death due to any cause.
The change in phosphorylated Erk kinase activity relative to total Erk kinase activity	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
The change in phosphorylated MEK kinase activity relative to total MEK kinase activity	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
The change in the expression of the copper transporter CTR1	Up to 2 years	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	Up to 2 years

Trial Locations

Locations (1)

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States