Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

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

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: 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

Relevance to patient case: possibly relevant