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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/NCT01765543




Registration number
NCT01765543
Ethics application status
Date submitted
9/01/2013
Date registered
10/01/2013
Date last updated
15/12/2016

Titles & IDs
Public title
A Pharmacokinetics (PK) Study to Investigate the Effect of Rifampin on PK of Vemurafenib (Zelboraf)
Scientific title
A Phase I, Open-Label, Multicenter, Three-Period, One-Sequence Study to Investigate the Effect of Rifampin on the Pharmacokinetics of a Single Oral Dose of 960 mg of Vemurafenib
Secondary ID [1] 0 0
2012-003142-33
Secondary ID [2] 0 0
GO28052
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 - Rifampin
Treatment: Drugs - Vemurafenib

Experimental: Vemurafenib + Rifampin - There will be 3 intervention periods in the study: Period A (Days 1 to 7), Period B (Days 8 to 16), and Period C (Days 17 to 24). Participants, after an overnight fast of at least 10 hours, will receive vemurafenib at a dose of 960 milligrams (mg) as film-coated tablets orally alone on Day 1 (Period A); with rifampin (at a dose of 600 mg as capsules orally) on Day 17 (Period C); and rifampin alone at a dose of 600 mg as capsules orally once daily will be administered from Days 8 through 16 (Period B) and from Days 18 through 23 (Period C).


Treatment: Drugs: Rifampin
Rifampin at a dose of 600 mg as capsules orally once daily will be administered from Days 8 through 23 (Periods B and C).

Treatment: Drugs: Vemurafenib
Participants, after an overnight fast of at least 10 hours, will receive vemurafenib at a dose of 960 mg as film-coated tablets orally on Day 1 (Period A) and on Day 17 (Period C).
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 Zero to the Last Measurable Concentration Time Point (AUClast) of Vemurafenib
Timepoint [1] 0 0
Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)
Primary outcome [2] 0 0
Area Under the Plasma Concentration Time-curve From Zero to Extrapolated Infinite Time (AUC[0-inf]) of Vemurafenib
Timepoint [2] 0 0
Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)
Primary outcome [3] 0 0
Maximum Observed Plasma Concentration (Cmax) of Vemurafenib
Timepoint [3] 0 0
Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)

Eligibility
Key inclusion criteria
- Participants with either unresectable Stage IIIc or Stage IV metastatic melanoma
positive for the BRAF V600 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 Deoxyribonucleic acid (DNA) sequencing method, and who have no
acceptable standard treatment options

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

- Life expectancy of greater than or equal to (>/=) 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 participants of childbearing potential and male participants with partners of
childbearing potential must agree to always use 2 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

- Requirement for immediate or urgent treatment with daily vemurafenib and for whom the
intermittent schedule of vemurafenib employed during the 24-day period for this trial
is not clinically acceptable

- Allergy or hypersensitivity to components of the vemurafenib formulation

- Experimental therapy within 4 weeks prior to first dose of study drug

- Major surgical procedure or significant traumatic injury within 14 days prior to first
dose of study drug, or anticipation of the need for major surgery during study
treatment

- 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 corrected QT interval (QTc) greater than (>)
450 milliseconds

- 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
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
1/07/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/11/2015
Sample size
Target
Accrual to date
Final
27
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
Brazil
State/province [5] 0 0
RS
Country [6] 0 0
Croatia
State/province [6] 0 0
Varazdin
Country [7] 0 0
Croatia
State/province [7] 0 0
Zagreb
Country [8] 0 0
Egypt
State/province [8] 0 0
Alexandria
Country [9] 0 0
Egypt
State/province [9] 0 0
Cairo
Country [10] 0 0
Egypt
State/province [10] 0 0
Dakahlia
Country [11] 0 0
Egypt
State/province [11] 0 0
Tanta
Country [12] 0 0
South Africa
State/province [12] 0 0
Cape Town
Country [13] 0 0
South Africa
State/province [13] 0 0
Port Elizabeth

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 rifampin on the PK of vemurafenib in participants 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. 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/NCT01765543
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