Clinical Trial: Intermittent Selumetinib for Uveal Melanoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Multi-Center Phase Ib Study of Intermittent Dosing of the MEK Inhibitor, Selumetinib, in Patients With Advanced Uveal Melanoma Not Previously Treated With a MEK Inhibitor

Brief Summary: The purpose of this study is to find out what effects, good and/or bad, intermittent dosing of the drug Selumetinib will have on subjects with uveal melanoma. Selumetinib is a drug that blocks (or turns off) methyl ethyl ketone (MEK), a protein activated in some uveal melanoma cells. Selumetinib is a MEK inhibitor. Blocking MEK may stop the cancer from growing.

Detailed Summary:

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, and arises from melanocytes within the choroid plexus of the eye. The development of metastasis is common and occurs in approximately 50% of patients with posterior UM within 15 years of initial diagnosis and treatment. As no effective systemic therapy has yet been identified for this disease, outcomes for metastatic UM are poor with a median survival of 12 months.

There is no FDA approved therapy for patients with advanced UM. Studies have shown that inhibition of the MAPK pathway with the MEK inhibitor selumetinib (hyd-sulfate AZD6244) is an effective therapy for uveal melanoma but despite this treatment, cures are not achieved. Although drugs such as selumetinib have been studied when patients take the treatment every day, research has shown that in some cases, it may be better to use the treatment on an intermittent schedule. Such a strategy may reduce the side effects, allow higher doses of the drug to be used, more completely block the MAPK pathway, and prevent the development of drug resistance mechanisms within the tumor.


Sponsor: Richard D. Carvajal

Current Primary Outcome: Maximum Tolerated Dose (MTD) of intermittent selumetinib [ Time Frame: Up to 2 years ]

MTD is defined as the dose associated with a target probability of dose limiting toxicity (DLT) of 25%. DLT will be assessed over the course of first two cycles of treatment (i.e., 8 weeks) for dose selection for subsequent patient treatment initiation.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Number of adverse events (AEs) [ Time Frame: Up to 2 years ]
    Number of AE throughout the study to assess the safety and tolerability of intermittent selumetinib
  • Number of serious adverse events (SAEs) [ Time Frame: Up to 2 years ]
    Number of SAE throughout the study to assess the safety and tolerability of intermittent selumetinib
  • Number of subjects with Dose Limiting Toxicity (DLT) [ Time Frame: Up to 2 years ]
    Number of subjects with DLT throughout the study to assess the safety and tolerability of intermittent selumetinib


Original Secondary Outcome: Same as current

Information By: Columbia University

Dates:
Date Received: May 10, 2016
Date Started: September 2016
Date Completion: January 2018
Last Updated: December 15, 2016
Last Verified: December 2016