Trametinib With GSK2141795 in BRAF Wild-type Melanoma

Part of paid clinical trials in San Francisco, California.

Sponsor
Adil Daud
Study ID
NCT01941927
Phase
PHASE2
Status
Completed

Conditions

Eligibility Criteria

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

Interventions

  • Trametinib (GSK1120212) — DRUG
    Trametinib is a highly selective allosteric inhibitor of MEK1 and MEK2 activation and kinase activity.
  • GSK2141795 — DRUG
    GSK 2141795 is an ATP competitive subnanomolar pan-AKT inhibitor. In order to measure the true potency of GSK 2141795, potency (Ki\*) values were determined in a filter binding assay using lower enzyme concentrations (0.1, 0.7, and 0.2 nM for human AKT1, AKT2, and AKT3, respectively). Using a sandwich ELISA, GSK 2141795 inhibited phosphorylation of GSK-3β in BT474 and LNCaP cell lines with EC50 values of 143 and 34 nM, respectively. Since phosphorylation of GSK-3β can be modulated by other enzymes (PKA, PKC, and RSK),cellular activity of GSK 2141795 was evaluated using a phospho-PRAS40 ELISA. GSK 2141795 inhibited the phosphorylation of PRAS40 with EC50 values of 39 and 55 nM for BT474 and LNCaP cells, respectively.

Study Details

This is a multicenter phase II clinical study of trametinib in combination with GSK2141795 in patients with BRAF wild-type mutation melanoma. All patients will receive continuous dosing of trametinib (2 mg) in combination with GSK2141795 (25 mg) oral daily until progression of disease, withdrawal of consent, or the development of intolerable treatment associated toxicity. Imaging (CT or MRI) will be performed within 7 days prior to day 1 of Odd Cycles, starting with Cycle 3. Patients may continue treatment with trametinib in combination with GSK2141795 on trial until disease progression or the development of unacceptable toxicity that does not improve with maximal supportive care or dose reduction per protocol. Treatment-associated adverse events will be assessed based on clinical and laboratory findings using the Common Toxicity Criteria for Adverse Events, version 4.0. Adverse event (AE) assessments will be performed every week through cycle 3 day 1, and on day 1 for every cycle thereafter. AEs and Serious adverse events (SAE)s will be monitored by UCSF's Data Safety Monitoring Committee. Safety assessments will include medical history, physical examination, Complete Blood Count (CBC) with differential, chemistries panel, thyroid function and pregnancy tests, ECGs, and ophthalmology evaluations. Screening assessments will also include a transthoracic echocardiogram or multiple-gated acquisition (MUGA) scan, and brain imaging. It is estimated that 48 patients will complete the study.

Key Dates

Start date
Sep 10, 2013
Status verified
Jan 2020
Primary completion
Oct 14, 2014
Completion
May 3, 2017

Study Design

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

Arms

  • Experimental: Trametinib, GSK2141795
    Trametinib (GSK1120212) * Oral * 2 mg * Daily * Number of Cycles: until progression or unacceptable toxicity develops GSK2141795 * Oral * 25 mg * Daily * Number of Cycles: until progression or unacceptable toxicity develops

Primary Outcome Measure

Objective Response Rate (ORR) [ Time Frame: Up to 2 years from beginning of therapy ]

Locations (2)

FacilityCityStateZIPSite coordinators
University of California, San FranciscoSan FranciscoCalifornia94115-
Memorial Sloan-Kettering Cancer CenterNew YorkNew York10065-

Find similar trials in San Francisco, CA

By condition
Melanoma
By specialty
OncologySkin cancerDermatology
By research site
University of California, San Francisco· San Francisco, CAMemorial Sloan-Kettering Cancer Center· New York, NY

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