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A Pharmacokinetics (PK) Study to Investigate the Effect of Rifampin on PK of Vemurafenib (Zelboraf)

NCT01765543

Description:

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).

Related Conditions:
  • Malignant Solid Tumor
  • Melanoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: GO28052
  • SECONDARY ID: 2012-003142-33
  • NCT ID: NCT01765543

Conditions

  • Malignant Melanoma, Neoplasms

Interventions

DrugSynonymsArms
RifampinVemurafenib + Rifampin
VemurafenibRO5185426, ZelborafVemurafenib + Rifampin

Purpose

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 Arms

NameTypeDescriptionInterventions
Vemurafenib + RifampinExperimentalThere 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).
  • Rifampin
  • Vemurafenib

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Area Under the Plasma Concentration Time-curve From Zero to the Last Measurable Concentration Time Point (AUClast) of Vemurafenib
Time Frame: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)
Safety Issue:
Description:AUClast is the area under the vemurafenib plasma concentration versus time curve from time zero to the time of last measured concentration of vemurafenib (Tlast). Area under the curve (AUC) is a measure of the plasma concentration of a drug over time. AUClast is presented in micrograms times (*) hour per milliliter (mcg*h/mL).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Hoffmann-La Roche

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