Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01844674




Registration number
NCT01844674
Ethics application status
Date submitted
29/04/2013
Date registered
1/05/2013
Date last updated
20/03/2017

Titles & IDs
Public title
A Study on the Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Tizanidine in Patients With BRAFV600 Mutation-Positive Metastatic Malignancies
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 Tizanidine (a CYP1A2 Substrate) in Patients With BRAFV600 Mutation-Positive Metastatic Malignancy
Secondary ID [1] 0 0
2012-003705-94
Secondary ID [2] 0 0
GO28396
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Melanoma, Neoplasms 0 0
Hepatitis C 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

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

Experimental: Pharmacokinetic Population - All participants will receive a 3-period treatment including single-dose tizanidine on Day 1, twice-daily vemurafenib on Days 2 to 21, and both agents together on Day 22.

Experimental: VX-135 High Dose with Daclatasvir - 12 weeks of a high dose of VX-135 in combination with Daclatasvir

Experimental: VX-135 Low Dose with Daclatasvir - 12 weeks of a low dose of VX-135 in combination with Daclatasvir


Treatment: Drugs: Tizanidine
Participants will receive tizanidine as single oral doses, 2 milligrams (mg) on Day 1 and repeated on Day 22, each following an overnight fast \>/= 10 hours.

Treatment: Drugs: Vemurafenib
Participants will receive vemurafenib as multiple oral doses, 960 mg twice daily on Days 2 to 22.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Area under the concentration-time curve (AUC)
Timepoint [1] 0 0
Pre-dose and up to 12 hours post-dose
Primary outcome [2] 0 0
Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Maximum plasma concentration (Cmax)
Timepoint [2] 0 0
Pre-dose and up to 12 hours post-dose
Primary outcome [3] 0 0
Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Time to maximum plasma concentration (Tmax)
Timepoint [3] 0 0
Pre-dose and up to 12 hours post-dose
Primary outcome [4] 0 0
Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Terminal half-life (t1/2)
Timepoint [4] 0 0
Pre-dose and up to 12 hours post-dose
Primary outcome [5] 0 0
Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Apparent clearance (CL/F)
Timepoint [5] 0 0
Pre-dose and up to 12 hours post-dose
Primary outcome [6] 0 0
The safety and tolerability as assessed by adverse events (AEs), vital signs, 12-lead electrocardiograms (ECGs), echocardiograms, and laboratory assessments
Timepoint [6] 0 0
Up to 64 weeks
Secondary outcome [1] 0 0
Safety: Incidence, nature and severity of adverse events and serious adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0
Timepoint [1] 0 0
Up to approximately 9 months
Secondary outcome [2] 0 0
The proportion of subjects who have a sustained virologic response (SVR; i.e., HCV RNA concentration below the lower limit of quantitation [<LLOQ; <25 IU/mL]) at 4 weeks after the last planned dose of treatment (SVR4)
Timepoint [2] 0 0
Up to 20 Weeks
Secondary outcome [3] 0 0
The proportion of subjects who have an SVR at 12 weeks after the last planned dose of treatment (SVR12)
Timepoint [3] 0 0
Up to 28 weeks
Secondary outcome [4] 0 0
The proportion of subjects who have an SVR at 44 weeks after the last planned dose of treatment (SVR24)
Timepoint [4] 0 0
Up to 40 weeks
Secondary outcome [5] 0 0
The proportion of subjects who have virologic relapse
Timepoint [5] 0 0
Up to 64 weeks
Secondary outcome [6] 0 0
The proportion of subjects who have virologic breakthrough
Timepoint [6] 0 0
Up to 16 weeks
Secondary outcome [7] 0 0
The amino acid sequence of the nonstructural NS5A and NS5B proteins in subjects who have treatment failure
Timepoint [7] 0 0
Up to 64 weeks
Secondary outcome [8] 0 0
The proportion of subjects who achieve SVR12 by HCV genotype 1 subtype (1a versus non-1a)
Timepoint [8] 0 0
Up to 28 weeks
Secondary outcome [9] 0 0
The proportion of subjects who achieve SVR12 by IL-28B genotype (CC versus non-CC)
Timepoint [9] 0 0
Up to 28 weeks

Eligibility
Key inclusion criteria
* Adults 18 to 70 years of age, inclusive
* Unresectable Stage IIIc or IV metastatic melanoma positive for the BRAFV600 mutation or other malignant tumor type which harbors a V600 activating mutation of BRAF, as determined by Cobas 4800 BRAFV600 Mutation Test or a DNA sequencing method
* Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
* Life expectancy greater than or equal to (>/=) 12 weeks
* Participant has not consumed tobacco or nicotine-containing products for 42 days prior to first dose of study drug, and must agree to refrain from such products while on study
* Adequate hematologic, renal and liver function
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
* History of or current clinically significant cardiac or pulmonary dysfunction, including current uncontrolled Grade >/= 2 hypertension or unstable angina
* Current dyspnea at rest due to complications of advanced malignancy or any requirement for supplemental oxygen
* Active central nervous system lesions (participants with radiographically unstable, symptomatic lesions)
* Participants with CYP1A2 gene mutation (-3113G->A), either in one or two alleles
* Allergy or hypersensitivity to vemurafenib or tizanidine formulations
* Current severe uncontrolled systemic disease
* Inability or unwillingness to swallow pills
* History of malabsorption or other condition that would interfere with enteral absorption of study treatment
* History of clinically significant liver disease (including cirrhosis), current alcohol abuse, or human immunodeficiency (HIV) infection requiring antiretroviral treatment, acquired immune deficiency syndrome (AIDS)-related illness, or active hepatitis B or C
* Pregnant or breastfeeding women

Study design
Purpose of the study
Other
Allocation to intervention
NA
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
2/09/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/08/2014
Sample size
Target
Accrual to date
Final
18
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
North Carolina
Country [4] 0 0
Brazil
State/province [4] 0 0
RJ
Country [5] 0 0
Brazil
State/province [5] 0 0
RS
Country [6] 0 0
Canada
State/province [6] 0 0
Quebec
Country [7] 0 0
Cyprus
State/province [7] 0 0
Nicosia
Country [8] 0 0
Korea, Republic of
State/province [8] 0 0
Seoul
Country [9] 0 0
New Zealand
State/province [9] 0 0
Auckland
Country [10] 0 0
New Zealand
State/province [10] 0 0
Christchurch

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT01844674