Study of Trametinib and Nab-paclitaxel in Patients With Melanoma

May 28, 2019 updated by: SCRI Development Innovations, LLC

Phase I Study of Trametinib and Nab-paclitaxel in Patients With Melanoma

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Denver, Colorado, United States, 80218
        • Colorado Blood Cancer Institute
    • Florida
      • Sarasota, Florida, United States, 34232
        • Florida Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology PLLC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: trametinib and nab-paclitaxel
Trametinib will be dosed at 1mg, 1.5mg, and 2mg orally (PO) daily based on Phase I data of this drug as a single agent. All patients entering this study will receive intravenous (IV) nab-paclitaxel on Day 1, 8, and 15. Dose levels will be assigned to each patient, and dose escalation decisions will be based on the evaluation of safety data from the prior cohort.
Drug: nab-paclitaxel
Other Names:
  • Abraxane
Drug: trametinib
Other Names:
  • Mekinist

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with Adverse Events (AEs) as a Measure of Safety and Tolerability
Time Frame: weekly for the first 4 weeks
The maximum tolerated dose (MTD) of the drug combination will be determined as the highest dose at which ≤1 of 6 patients experience a dose limiting toxicity (DLT) during one cycle (28 days) of therapy.
weekly for the first 4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

SCRI Development Innovations, LLC

Collaborators

GlaxoSmithKline
Celgene

Investigators

  • Study Chair: Jeffrey R. Infante, MD, SCRI Development Innovations, LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

December 1, 2015

Primary Completion (Actual)

January 20, 2016

Study Completion (Actual)

January 20, 2016

Study Registration Dates

First Submitted

November 21, 2014

First Submitted That Met QC Criteria

November 24, 2014

First Posted (Estimate)

November 25, 2014

Study Record Updates

Last Update Posted (Actual)

May 30, 2019

Last Update Submitted That Met QC Criteria

May 28, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SCRI MEL 40

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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