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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01765569




Registration number
NCT01765569
Ethics application status
Date submitted
9/01/2013
Date registered
10/01/2013
Date last updated
23/09/2015

Titles & IDs
Public title
A Pharmacokinetics Study to Investigate the Effect of Vemurafenib on Digoxin in Patients With BRAFV600 Mutation-Positive Metastatic Melanoma
Scientific 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
Secondary ID [1] 0 0
2012-003459-13
Secondary ID [2] 0 0
GO28394
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Melanoma, Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Digoxin
Treatment: Drugs - Vemurafenib

Experimental: Vemurafenib + Digoxin - 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.


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

Treatment: Drugs: Vemurafenib
Participants received vemurafenib 960 mg tablet orally BID from Day 8 to Day 35.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of Digoxin
Timepoint [1] 0 0
Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose
Primary outcome [2] 0 0
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Digoxin
Timepoint [2] 0 0
Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose
Primary outcome [3] 0 0
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC24) of Digoxin
Timepoint [3] 0 0
Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose
Primary outcome [4] 0 0
Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC168) of Digoxin
Timepoint [4] 0 0
Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose
Primary outcome [5] 0 0
Maximum Plasma Concentration (Cmax) of Digoxin
Timepoint [5] 0 0
Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose
Primary outcome [6] 0 0
Time to Maximum Plasma Concentration (Tmax) of Digoxin
Timepoint [6] 0 0
Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose
Primary outcome [7] 0 0
Terminal Half-Life (t1/2) of Digoxin
Timepoint [7] 0 0
Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose
Primary outcome [8] 0 0
Apparent Clearance (CL/F) of Digoxin
Timepoint [8] 0 0
Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/06/2014
Sample size
Target
Accrual to date
Final
29
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Belarus
State/province [1] 0 0
Minsk District
Country [2] 0 0
Belarus
State/province [2] 0 0
Minsk
Country [3] 0 0
Belarus
State/province [3] 0 0
Vitebsk
Country [4] 0 0
Israel
State/province [4] 0 0
Haifa
Country [5] 0 0
Israel
State/province [5] 0 0
Tel Aviv
Country [6] 0 0
Israel
State/province [6] 0 0
Tel Hashomer
Country [7] 0 0
Korea, Republic of
State/province [7] 0 0
Daegu
Country [8] 0 0
Korea, Republic of
State/province [8] 0 0
Seoul
Country [9] 0 0
Russian Federation
State/province [9] 0 0
Kazan
Country [10] 0 0
Russian Federation
State/province [10] 0 0
Moscow
Country [11] 0 0
Russian Federation
State/province [11] 0 0
St. Petersburg
Country [12] 0 0
South Africa
State/province [12] 0 0
Johannesburg

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01765569
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries