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

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Digoxin

Vemurafenib

About this trial

This is an interventional treatment trial for Malignant Melanoma, Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Vemurafenib + Digoxin

Arm Description

Single oral dose of digoxin 0.25 mg tablet on Day 1 in Period A, followed by vemurafenib 960 mg tablet orally BID from Day 8 to Day 28 in Period B, and then single oral dose of digoxin 0.25 mg on Day 29, and vemurafenib 960 mg orally BID from Day 29 to Day 35 in Period C.

Outcomes

Primary Outcome Measures

Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of Digoxin

AUClast = Area under the plasma-concentration time curve from time zero to the last measurable plasma concentration which is presented in hour*nanogram per milliliter (hour*ng/mL). Hour 0 (H0) signified pre-dose sampling.

Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Digoxin

Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC24) of Digoxin

Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC168) of Digoxin

Maximum Plasma Concentration (Cmax) of Digoxin

Time to Maximum Plasma Concentration (Tmax) of Digoxin

Terminal Half-Life (t1/2) of Digoxin

Apparent Clearance (CL/F) of Digoxin

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

Secondary Outcome Measures

Full Information

NCT ID

NCT01765569

First Posted

January 9, 2013

Last Updated

August 24, 2015

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT01765569

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2015

Overall Recruitment Status

Completed

Study Start Date

July 2013 (undefined)

Primary Completion Date

June 2014 (Actual)

Study Completion Date

June 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

5. Study Description

Brief Summary

This open-label, multi-center, three-period, one sequence study will investigate the effect of vemurafenib on the pharmacokinetics of digoxin in patients with unresectable BRAFV600-mutation positive metastatic melanoma or other malignant tumor type that harbors a V600-activating mutation of BRAF without acceptable standard treatment options. Patients will receive multiple doses of vemurafenib in Periods B and C and a single dose of digoxin in Periods A and C. Eligible patients will have the option to continue treatment with vemurafenib as part of an extension study (NCT01739764). The anticipated time on study treatment is approximately 36 days.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Malignant Melanoma, Neoplasms

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

29 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Vemurafenib + Digoxin

Arm Type

Experimental

Arm Description

Single oral dose of digoxin 0.25 mg tablet on Day 1 in Period A, followed by vemurafenib 960 mg tablet orally BID from Day 8 to Day 28 in Period B, and then single oral dose of digoxin 0.25 mg on Day 29, and vemurafenib 960 mg orally BID from Day 29 to Day 35 in Period C.

Intervention Type

Drug

Intervention Name(s)

Digoxin

Intervention Description

Participants received single oral dose of digoxin 0.25 mg tablet on Day 1 and Day 29.

Intervention Type

Drug

Intervention Name(s)

Vemurafenib

Intervention Description

Participants received vemurafenib 960 mg tablet orally BID from Day 8 to Day 35.

Primary Outcome Measure Information:

Title

Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of Digoxin

Description

AUClast = Area under the plasma-concentration time curve from time zero to the last measurable plasma concentration which is presented in hour*nanogram per milliliter (hour*ng/mL). Hour 0 (H0) signified pre-dose sampling.

Time Frame