Clinical trial NCT01765543: A Pharmacokinetics (PK) Study to Investigate the Effect of Rifampin on PK of Vemurafenib (Zelboraf)
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malignant Melanoma, Neoplasms
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-01-10
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

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

Primary outcomes:
measure: Area Under the Plasma Concentration Time-curve From Zero to the Last Measurable Concentration Time Point (AUClast) of Vemurafenib
timeFrame: 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)
measure: Area Under the Plasma Concentration Time-curve From Zero to Extrapolated Infinite Time (AUC[0-inf]) of Vemurafenib
timeFrame: 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)
measure: Maximum Observed Plasma Concentration (Cmax) of Vemurafenib
timeFrame: 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)
Secondary outcomes:
Other outcomes:
measure: Time to Reach Cmax (Tmax) of Vemurafenib
timeFrame: 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)
measure: Plasma Elimination Half Life (t1/2) of Vemurafenib
timeFrame: 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)
measure: Plasma Apparent Clearance (CL/F) of Vemurafenib
timeFrame: 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)
measure: Area Under the Plasma Concentration Time-curve From Zero to 168 Hours [AUC(0-168)] of Vemurafenib
timeFrame: 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)
measure: Percent Extrapolated AUC(0-inf) (AUCpeo) of Vemurafenib
timeFrame: 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)
Locations:
city: Rogers
country: United States
state: Arkansas
city: Pleasant Hill
country: United States
state: California
city: Middletown
country: United States
state: Ohio
city: Dallas
country: United States
state: Texas
city: Porto Alegre
country: Brazil
state: RS
city: Porto Alegre
country: Brazil
state: RS
city: Porto Alegre
country: Brazil
state: RS
city: Varazdin
country: Croatia
city: Zagreb
country: Croatia
city: Alexandria
country: Egypt
city: Cairo
country: Egypt
city: Dakahlia
country: Egypt
city: Tanta
country: Egypt
city: Cape Town
country: South Africa
city: Port Elizabeth
country: South Africa
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: