Clinical trial NCT02300935: Study of Trametinib and Nab-paclitaxel in Patients With Melanoma
Official title: Phase I Study of Trametinib and Nab-paclitaxel in Patients With Melanoma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Melanoma
Keywords: trametinib
nab-paclitaxel
Mekinist
Abraxane
unresectable
metastatic
Lead sponsor: SCRI Development Innovations, LLC
Sponsor class: OTHER
Collaborators: name: Celgene
name: GlaxoSmithKline
First posted: 2014-11-25
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will investigate the combination of two drugs, trametinib and nab-paclitaxel, in patients with advanced unresectable or metastatic melanoma. Each drug has shown activity in trials of patients with melanoma. However, the combination of these two drugs has not been studied. In this trial the investigators will determine the maximum dose of the drug combination to be administered to patients with advanced unresectable or metastatic melanoma and examine the safety profile of the drug combination.

Detailed description: While treatment for melanoma has evolved in the last few years, advanced/metastatic melanoma remains an aggressive disease with poor prognosis. Trametinib and nab-paclitaxel have demonstrated single-agent activity in Phase III trials of patients with melanoma. The investigators propose to investigate this drug combination in patients with advanced unresectable or metastatic melanoma. This open-label Phase I study is designed to determine the maximum tolerated dose (MTD), recommended Phase II dose (RP2D), and safety profile of trametinib and nab-paclitaxel given in combination. Patients with melanoma and known BRAF mutation status will receive escalating doses of trametinib and nab-paclitaxel to determine the MTD. Once the MTD is determined an additional 6 patients will be treated at the MTD to establish the dose for future studies.

Eligibility criteria: Inclusion Criteria:

* Adults (≥18 years) with histologically or cytologically-confirmed advanced unresectable or metastatic melanoma. BRAF mutation-positive and wild-type tumors are allowed.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Adequate hematologic, renal, and hepatic function
* Life expectancy ≥12 weeks
* Any pre-existing neuropathy must be \<grade 2 per Common Technology Criteria for Adverse Events (CTCAE) version 4.0

Exclusion Criteria:

* More than 1 prior cytotoxic chemotherapy regimen in the metastatic setting
* Prior MEK inhibitor therapy (prior BRAF inhibitor allowed)
* Prior nab-paclitaxel (prior taxane allowed)
* Use of an investigational anti-cancer drug within 21 days or 5 half-lives (whichever is shorter) prior to first dose. A minimum of 10 days after termination of investigational drug is required. Any drug-related toxicity should have resolved to Grade 1 or baseline.
* Symptomatic or untreated brain metastases
* History of retinal vein occlusion (RVO)

Primary outcomes:
measure: Number of patients with Adverse Events (AEs) as a Measure of Safety and Tolerability
timeFrame: weekly for the first 4 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Sarasota
country: United States
facility: Florida Cancer Center
state: Florida
city: Nashville
country: United States
facility: Tennessee Oncology PLLC
state: Tennessee
Study officials:
affiliation: SCRI Development Innovations, LLC
name: Jeffrey R. Infante, MD
role: STUDY_CHAIR
References: