LCCC 1128: Open Label Phase II Trial of the BRAF Inhibitor (Dabrafenib) and the MEK Inhibitor (Trametinib) in Unresectable Stage III and Stage IV BRAF Mutant Melanoma; Correlation of Resistance With the Kinome and Functional Mutations

Part of paid clinical trials in Chapel Hill, North Carolina.

Sponsor
UNC Lineberger Comprehensive Cancer Center
Study ID
NCT01726738
Phase
PHASE2
Status
Completed

Conditions

  • BRAF Mutant Melanoma
  • Stage III Melanoma
  • Stage IV Melanoma
  • Unresectable Melanoma

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • BRAF inhibitor dabrafenib and MEK inhibitor trametinib — DRUG
    Patients will receive the BRAF inhibitor dabrafenib and MEK inhibitor trametinib orally at the RP2D determined in the Phase I/II study (BRF113220): trametinib 2mg QD and dabrafenib 150 mg BID on a continuous basis. A cycle will be defined as 3 weeks in duration. Cycles will be repeated until disease progression (clinical or radiological). Patients may remain on treatment after progression (at the discretion of the investigator) as long as they are still experiencing clinical benefit.

Study Details

This phase II study in 20 patients with BRAFV600E mutant, unresectable stage III/IV melanoma is designed to explore the mechanisms by which tumors acquire resistance to the combination of a BRAF inhibitor (dabrafenib) and MEK inhibitor (trametinib). Tissue will be collected at baseline and at progression.If a subject is removed from the study for one of a variety of reasons including, but not limited to, an inability to tolerate the combination of dabrafenib and trametinib, a need to receive other therapy or completion of 3-years of study treatment without progression, and the subject later receives, as part of his/her standard of care, the combination of dabrafenib and trametinib and progresses on the standard of care regimen, then the subject may be contacted by the treating physician to be put back on to the LCCC 1128 protocol and have a progression biopsy at this progression time point. Markers of resistance will be explored by performing near kinome-wide profiling on tumor samples, and in patients who co-enroll in institutional protocol LCCC1108, by sequencing tumors using NextGen DNA sequencing technology. Overall response rate and duration to this combination will also be assessed.

Key Dates

Start date
Apr 4, 2013
Status verified
Sep 2020
Primary completion
Nov 3, 2017
Completion
Sep 17, 2020

Study Design

Enrollment
17 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: BRAF (dabrafenib) and MEK (trametinib) inhibitors
    Patients will receive the BRAF inhibitor dabrafenib and MEK inhibitor trametinib orally at the RP2D determined in the Phase I/II study (BRF113220): trametinib 2mg QD and dabrafenib 150 mg BID on a continuous basis. A cycle will be defined as 3 weeks in duration. Cycles will be repeated until disease progression (clinical or radiological). Patients may remain on treatment after progression (at the discretion of the investigator) as long as they are still experiencing clinical benefit.

Primary Outcome Measure

Change in Kinase Expression [ Time Frame: Baseline and One year post treatment ]

Locations (1)

FacilityCityStateZIPSite coordinators
Lineberger Comprehensive Cancer Center, University of North CarolinaChapel HillNorth Carolina27599-

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Lineberger Comprehensive Cancer Center, University of North Carolina· Chapel Hill, NC

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