A Pharmacokinetics Study to Investigate the Effect of Vemurafenib on Digoxin in Patients With BRAFV600 Mutation-Positive Metastatic Melanoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01765569
First received: January 9, 2013
Last updated: October 6, 2014
Last verified: October 2014
  Purpose

This open-label, multi-center, three-period, one sequence study will investigate the effect of vemurafenib on the pharmacokinetics of digoxin in patients with u nresectable BRAFV600-mutation positive metastatic melanoma or other malignant tu mor type that harbors a V600-activating mutation of BRAF without acceptable stan dard treatment options. Patients will receive multiple doses of vemurafenib in P eriods B and C and a single dose of digoxin in Periods A and C. Eligible patient s will have the option to continue treatment with vemurafenib as part of an exte nsion study (NCT01739764). The anticipated time on study treatment is approximat ely 36 days.


Condition Intervention Phase
Malignant Melanoma, Neoplasms
Drug: digoxin
Drug: vemurafenib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Open-Label, Multicenter, 3-Period, Fixed-Sequence Study To Investigate The Effect Of Vemurafenib On The Pharmacokinetics Of A Single Dose Of Digoxin In Patients With BRAFV600 Mutation-Positive Metastatic Malignancy

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Pharmacokinetics: Area under the concentration time curve [ Time Frame: Approximately 36 days ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Maximum plasma concentration [ Time Frame: Approximately 36 days ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Time to maximum plasma concentration [ Time Frame: Approximately 36 days ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Terminal half-life [ Time Frame: Approximately 36 days ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Apparent clearance [ Time Frame: Approximately 36 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety: Incidence of adverse events [ Time Frame: Approximately 36 days ] [ Designated as safety issue: No ]

Enrollment: 29
Study Start Date: July 2013
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Digoxin treatment Drug: digoxin
Single dose of digoxin in Periods A and C
Experimental: Vemurafenib treatment Drug: vemurafenib
Multiple doses of vemurafenib in Periods B and C

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients >= 18 years old
  • Patients with either unresectable Stage IIIc or Stage IV metastatic melanoma positive for the BRAFV600 mutation or other malignant tumor type that harbors a V600-activating mutation of BRAF, as determined by results of cobas® 4800 BRAF V600 mutation test or a DNA sequencing method, and who have no acceptable standard treatment options
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
  • Life expectancy >= 12 weeks
  • Full recovery from the effects of any major surgery or significant traumatic injury within 14 days prior to the first dose of study treatment
  • Adequate hematologic and end organ function
  • Female patients of childbearing potential and male patients with partners of childbearing potential must agree to always use two effective methods of contraception
  • Negative serum pregnancy test within 7 days prior to commencement of dosing in women of childbearing potential

Exclusion Criteria:

  • Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of first dose of study drug
  • Prior anti-cancer therapy within 28 days before the first dose of study drug
  • History of clinically significant cardiac or pulmonary dysfunction
  • History of symptomatic congestive heart failure of any New York Heart Association class or serious cardiac arrhythmia requiring treatment
  • History of myocardial infarction within 6 months prior to first dose of study drug
  • Current dyspnea at rest, owing to complications of advanced malignancy or any requirement for supplemental oxygen to perform activities of daily living
  • History of congenital long QT syndrome or QTc > 450 ms
  • Current digoxin therapy or anticipated requirement to take digoxin therapy during the study
  • Active central nervous system lesions
  • Uncontrolled or poorly controlled diabetes
  • Current severe, uncontrolled systemic disease
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01765569

Locations
Belarus
Minsk, Belarus, BU-220013
Minsk District, Belarus, 223040
Vitebsk, Belarus, BU-210603
Israel
Haifa, Israel, 31096
Tel Aviv, Israel, 6423906
Tel Hashomer, Israel, 52661
Korea, Republic of
Daegu, Korea, Republic of, 702-911
Seoul, Korea, Republic of, 135-710
Seoul, Korea, Republic of, 110744
Russian Federation
Kazan, Russian Federation, 420029
Moscow, Russian Federation, 115478
St. Petersburg, Russian Federation, 197758
South Africa
Johannesburg, South Africa, 2193
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01765569     History of Changes
Other Study ID Numbers: GO28394, 2012-003459-13
Study First Received: January 9, 2013
Last Updated: October 6, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Digoxin
Anti-Arrhythmia Agents
Cardiotonic Agents
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014