A Pharmacokinetics Study to Investigate the Effect of Rifampin on Vemurafenib in Patients With BRAFV600 Mutation-Positive Metastatic Malignancy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01765543
First received: January 9, 2013
Last updated: August 1, 2016
Last verified: August 2016
  Purpose
This open-label, multi-center, three-period, one sequence study will investigate the effect of rifampin on the pharmacokinetics of vemurafenib in patients 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. Patients will receive a single dose of vemurafenib in Periods A and C and multiple doses of rifampin in Periods B and C. Eligible patients will have the option to continue treatment with vemurafenib as part of an extension study (NCT01739764). The anticipated time on study treatment is approximately 24 days.

Condition Intervention Phase
Malignant Melanoma, Neoplasms
Drug: rifampin
Drug: vemurafenib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Pharmacokinetics: Area under the concentration time curve [ Time Frame: Approximately 24 days ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Maximum plasma concentration [ Time Frame: Approximately 24 days ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Time to maximum plasma concentration [ Time Frame: Approximately 24 days ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Terminal half-life [ Time Frame: Approximately 24 days ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Apparent clearance [ Time Frame: Approximately 24 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety: Incidence of adverse events [ Time Frame: Approximately 24 days ] [ Designated as safety issue: No ]

Enrollment: 42
Study Start Date: July 2013
Study Completion Date: January 2016
Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rifampin treatment Drug: rifampin
multiple doses of rifampin in Period B and C
Experimental: Vemurafenib treatment Drug: vemurafenib
single dose of vemurafenib in Period A and C

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients >= 18 years old
  • Patients with either unresectable Stage IIIc or Stage IV metastatic melanoma positive for the BRAFV600 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 DNA sequencing method, and who have no acceptable standard treatment options
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
  • Life expectancy >= 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 patients of childbearing potential and male patients with partners of childbearing potential must agree to always use two 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 QTc > 450 ms
  • Active central nervous system lesions
  • Uncontrolled or poorly controlled diabetes
  • Current severe, uncontrolled systemic disease
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01765543

Locations
United States, Arkansas
Rogers, Arkansas, United States, 72758
United States, California
Pleasant Hill, California, United States, 94523
United States, Ohio
Middletown, Ohio, United States, 45042
United States, Texas
Dallas, Texas, United States, 75246
Brazil
Porto Alegre, RS, Brazil, 90020-090
Porto Alegre, RS, Brazil, 90035-003
Porto Alegre, RS, Brazil, 90840-440
Croatia
Varazdin, Croatia, 42000
Zagreb, Croatia, 10000
Egypt
Alexandria, Egypt, 21131
Cairo, Egypt, 11796
Dakahlia, Egypt, 324
Tanta, Egypt
South Africa
Cape Town, South Africa, 7570
Port Elizabeth, South Africa, 6045
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01765543     History of Changes
Other Study ID Numbers: GO28052  2012-003142-33 
Study First Received: January 9, 2013
Last Updated: August 1, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Rifampin
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers
Cytochrome P-450 CYP3A Inducers

ClinicalTrials.gov processed this record on August 29, 2016