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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/NCT01851824




Registration number
NCT01851824
Ethics application status
Date submitted
3/05/2013
Date registered
13/05/2013
Date last updated
2/11/2016

Titles & IDs
Public title
A Study of the Effect of Vemurafenib on the Pharmacokinetics of Acenocoumarol in Patients With BRAFV600 Mutation-Positive Metastatic Malignancy
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 ORAL DOSE OF ACENOCOUMAROL IN PATIENTS WITH BRAFV600 MUTATION-POSITIVE METASTATIC MALIGNANCY
Secondary ID [1] 0 0
2012-003706-27
Secondary ID [2] 0 0
GO28397
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 - acenocoumarol
Treatment: Drugs - vemurafenib

Experimental: Acenocoumarol + Vemurafenib -


Treatment: Drugs: acenocoumarol
4 mg single oral doses on Days 1 and 23

Treatment: Drugs: vemurafenib
960 mg orally bid, 20 days (Days 4-23)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Area under the concentration-time curve (AUC)
Timepoint [1] 0 0
Pre-dose and up to 72 hours post-dose
Primary outcome [2] 0 0
Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Maximum plasma concentration (Cmax)
Timepoint [2] 0 0
Pre-dose and up to 72 hours post-dose
Primary outcome [3] 0 0
Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Time to maximum plasma concentration (Tmax)
Timepoint [3] 0 0
Pre-dose and up to 72 hours post-dose
Primary outcome [4] 0 0
Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Terminal half-life (t1/2)
Timepoint [4] 0 0
Pre-dose and up to 72 hours post-dose
Primary outcome [5] 0 0
Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Apparent clearance (CL/F)
Timepoint [5] 0 0
Pre-dose and up to 72 hours post-dose
Secondary outcome [1] 0 0
Safety: Incidence of Adverse Events and Serious Adverse Events
Timepoint [1] 0 0
approximately 1.5 years

Eligibility
Key inclusion criteria
- Adult patients, 18-70 years of age

- Patients with either unresectable Stage IIIc or IV BRAFV600 mutation-positive
metastatic melanoma or other malignant BRAFV600 mutation-positive tumor type and who
have no acceptable standard treatment options

- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

- Full recovery from any major surgery or significant traumatic injury at least 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 female partners of
childbearing potential must agree to use 2 effective methods of contraception as
defined by protocol during the course of the study and for at least 6 months after
completion of study treatment
Minimum age
18 Years
Maximum age
70 Years
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 Day 1

- Prior anti-cancer therapy within 28 days (6 weeks for nitrosureas or mitocyn C, or 14
days for hormonal therapy or kinase inhibitors) before the first dose of study
treatment Day 1

- Palliative radiotherapy within 2 weeks prior to first dose of study treatment Day 1

- Experimental therapy within 4 weeks prior to first dose of study treatment Day 1

- History of clinically significant cardiac or pulmonary dysfunction, including current
uncontrolled Grade >/=2 hypertension or unstable angina

- Current Grade >/=2 dyspnea or hypoxia or need for oxygen supplementation

- History of myocardial infarction within 6 months prior to first dose of study
treatment

- Active central nervous system lesions (i.e. participants with radiographically
unstable, symptomatic lesions)

- History of bleeding or coagulation disorders

- Allergy or hypersensitivity to vemurafenib or acenocoumarol formulations

- History of malabsorption or other condition that would interfere with the enteral
absorption of study treatment

- Participants with VKORC1 mutations (1639G→A, 1173C→T) in either one allele
(heterozygous)or two alleles (homozygous)

- Participants with CYP2C9*3 mutations in either one allele (heterozygous) or two
alleles (homozygous)

- History of clinically significant liver disease (including cirrhosis), current alcohol
abuse, or active hepatitis B or hepatitis C virus infection

- Human immunodeficiency virus (HIV) infection requiring antiretroviral treatment, or
AIDS-related illness

- Pregnant or lactating women

Study design
Purpose of the study
Allocation to intervention
N/A
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
1/08/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/06/2014
Sample size
Target
Accrual to date
Final
9
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
- Wodonga
Recruitment postcode(s) [1] 0 0
3690 - Wodonga
Recruitment outside Australia
Country [1] 0 0
Germany
State/province [1] 0 0
Buxtehude
Country [2] 0 0
Germany
State/province [2] 0 0
Essen
Country [3] 0 0
Germany
State/province [3] 0 0
Mannheim
Country [4] 0 0
Greece
State/province [4] 0 0
Crete
Country [5] 0 0
Greece
State/province [5] 0 0
Thessaloniki
Country [6] 0 0
Hungary
State/province [6] 0 0
Budapest
Country [7] 0 0
Netherlands
State/province [7] 0 0
Amsterdam
Country [8] 0 0
Netherlands
State/province [8] 0 0
Maastricht
Country [9] 0 0
Netherlands
State/province [9] 0 0
Utrecht
Country [10] 0 0
New Zealand
State/province [10] 0 0
Auckland
Country [11] 0 0
New Zealand
State/province [11] 0 0
Christchurch
Country [12] 0 0
Portugal
State/province [12] 0 0
Lisboa
Country [13] 0 0
Portugal
State/province [13] 0 0
Porto
Country [14] 0 0
Serbia
State/province [14] 0 0
Belgrade
Country [15] 0 0
Spain
State/province [15] 0 0
Barcelona
Country [16] 0 0
Spain
State/province [16] 0 0
Madrid

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, multicenter, 3-period, fixed-sequence study will evaluate the effect of
multiple doses of vemurafenib on the pharmacokinetics of a single dose of acenocoumarol in
participants with BRAFV600 mutation-positive metastatic malignancies. Participants will
receive a single dose of acenocoumarol 4 mg orally on Day 1 and Day 23, vemurafenib 960 mg
orally twice daily on Days 4-26. After completion of pharmacokinetic assessments on Day 26,
eligible participants will have the option to continue treatment with vemurafenib as part of
an extension study (GO28399 [NCT01739764]).
Trial website
https://clinicaltrials.gov/ct2/show/NCT01851824
Trial related presentations / publications
Public notes

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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01851824