A Phase 1B Clinical Trial of Trametinib Plus Digoxin in Patients With Unresectable or Metastatic BRAF Wild-type Melanoma
Status:
Completed
Trial end date:
2017-02-23
Target enrollment:
Participant gender:
Summary
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.