A Phase 1B Clinical Trial of Trametinib Plus Digoxin in Patients With Unresectable or Metastatic BRAF Wild-type Melanoma

Part of paid clinical trials in Dallas, Texas.

Sponsor
University of Texas Southwestern Medical Center
Study ID
NCT02138292
Phase
PHASE1
Status
Completed

Conditions

Eligibility Criteria

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

Interventions

  • Trametinib (2mg)/Digoxin (.25mg) — DRUG
    1. Trametinib (2mg) will be administered orally on a daily basis. 2. Digoxin (0.25mg) will be administered orally on a daily basis. On a 8 week cycle, duration of treatment can last from 8 to 104 weeks.

Study Details

The study is a prospective, single-arm, one-site therapeutic trial of the combination of trametinib plus digoxin for advanced melanoma. endpoints are toxicities assessed by nCi CTCae v4.1 within the first 8 weeks, responses measured by ReCiST v1.1 criteria every 8 weeks with scans and exams, tumor sensitivity to the drug combination quantified by tumor regressions in nSG mice, and correlations of response with tumor sensitivity, BRaF status, MaPK inhibitor exposure history, and tumor sodium pump expression. Treatment Dosage and administration Study Drugs: 1. Trametinib (2mg) will be administered orally on a daily basis. 2. Digoxin (0.25mg) will be administered orally on a daily basis. on a 8-week cycle, duration of treatment can last from 8 to 104 weeks. endpoints 1. Toxicities will be assessed via nCi's CTCae v4.1 toxicity criteria. DLTs will be defined based on the rate of drug-related (definitely or probably) grade 3-5 adverse events experienced within the first 8 weeks of study treatment. The MTD will be exceeded if more than 20% of patients on the study experience DLTs. 2. Responses will be measured by ReCiST v1.1 every 8 weeks. Response duration will be defined as time from first documented response until disease progression. PFS is time from treatment until disease progression. 3. Patient tumor sensitivity to the drug combination will be quantified by the amount of subcutaneous established tumor growth inhibition in nSG mice by 5d/week oral gavage with drugs. 4. Tumor nRaS status will be determined by tumor Dna extraction, PCR amplification of exons and Sanger sequencing of nRaS. 5. History of prior MaPK inhibitor therapies will document MeK inhibitor exposures. 6. Sodium pump subunit expression will be analyzed by pretreatment tumor immunohistochemistry and a qualitative 0 to 3+ grading system.

Key Dates

Start date
Jul 31, 2014
Status verified
May 2018
Primary completion
Feb 23, 2017
Completion
Feb 23, 2017

Study Design

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

Arms

  • Experimental: Trametinib (2mg)/Digoxin (0.25mg)
    1. Trametinib (2mg) will be administered orally on a daily basis. 2. Digoxin (0.25mg) will be administered orally on a daily basis. On a 8-week cycle, duration of treatment can last from 8 to 104 weeks.

Primary Outcome Measure

Dose Limiting Doxicities (DLTs) [ Time Frame: within the first 8 weeks of study treatment ]

Locations (1)

FacilityCityStateZIPSite coordinators
UT Southwestern Medical CenterDallasTexas75390-

Find similar trials in Dallas, TX

By condition
Melanoma
By specialty
OncologySkin cancerDermatology
By research site
UT Southwestern Medical Center· Dallas, TX

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