A Study on the Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Tizanidine in Patients With BRAFV600 Mutation-Positive Metastatic Malignancies

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01844674
First received: April 29, 2013
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

This open-label, multicenter, 3-period, fixed-sequence study will evaluate the e ffect of multiple oral doses of vemurafenib on the pharmacokinetics of a single oral dose of tizanidine in patients with BRAFV600 mutation-positive metastatic malignancies. Patients will receive a single oral dose of tizanidine on Day 1, v emurafenib orally twice daily on Days 2-21, and tizanidine and vemurafenib on Da y 22. Eligible patients will have the option to continue treatment with vemurafe nib as part of an extension study (NCT01739764).


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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: A PHASE I, OPEN-LABEL, MULTICENTER, 3- PERIOD, FIXED-SEQUENCE STUDY TO INVESTIGATE THE EFFECT OF VEMURAFENIB ON THE PHARMACOKINETICS OF SINGLE DOSE OF TIZANIDINE (A CYP1A2 SUBSTRATE) IN PATIENTS WITH BRAFV600 MUTATION-POSITIVE METASTATIC MALIGNANCY

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Area under the concentration-time curve (AUC) [ Time Frame: Pre-dose and up to 12 hours post-dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Maximum plasma concentration (Cmax) [ Time Frame: Pre-dose and up to 12 hours post-dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Time to maximum plasma concentration (Tmax) [ Time Frame: Pre-dose and up to 12 hours post-dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Terminal half-life (t1/2) [ Time Frame: Pre-dose and up to 12 hours post-dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Apparent clearance (CL/F) [ Time Frame: Pre-dose and up to 12 hours post-dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety: Incidence, nature and severity of adverse events and serious adverse events, graded according to the NCI CTAE (Version 4.0) [ Time Frame: approximately 1.5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 32
Study Start Date: September 2013
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PK Drug: vemurafenib
multiple oral doses
Drug: tizanidine
single oral doses

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients, 18 to 70 years of age, inclusive
  • Patients with either unresectable Stage IIIc or IV metastatic melanoma positive for the BRAFV600 mutation or other malignant tumor type which harbors a V600 activating mutation of BRAF, as determined by Cobas 4800 BRAFV600 Mutation Test or a DNA sequencing method
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
  • Life expectancy >/= 12 weeks
  • Patient has not consumed tobacco or nicotine-containing products for 6 weeks prior to first dose of study drug, and must agree to refrain from such products while on study
  • Adequate hematologic, renal and liver function

Exclusion Criteria:

  • Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of Day 1, period A
  • History of or current clinically significant cardiac or pulmonary dysfunction, including current uncontrolled Grade >/= 2 hypertension or unstable angina
  • Current dyspnea at rest due to complications of advanced malignancy or any requirement for supplemental oxygen
  • Active central nervous system lesions (i.e. patients with radiographically unstable, symptomatic lesions)
  • Patients with CYP2A2 gene mutation (-3113G->A)
  • Allergy or hypersensitivity to vemurafenib or tizanidine formulations
  • Current severe uncontrolled systemic disease
  • Inability or unwillingness to swallow pills
  • History of malabsorption or other condition that would interfere with enteral absorption of study treatment
  • History of clinically significant liver disease including cirrhosis), current alcohol abuse, or HIV infection requiring antiretroviral treatment, AIDS-related illness, or active hepatitis B or C
  • Active autoimmune disease
  • Pregnant or breastfeeding women
  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: NCT01844674

Contacts
Contact: Reference Study ID Number: GO28396 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com

Locations
United States, California
Completed
Pleasant Hill, California, United States, 94523
United States, Michigan
Recruiting
Detroit, Michigan, United States, 48201
United States, North Carolina
Recruiting
Durham, North Carolina, United States, 27710
Brazil
Recruiting
Rio de Janeiro, RJ, Brazil, 20560-120
Recruiting
Ijui, RS, Brazil, 98700-000
Recruiting
Passo Fundo, RS, Brazil, 99010-260
Recruiting
Porto Alegre, RS, Brazil, 90610-000
Canada, Quebec
Recruiting
Greenfield Park, Quebec, Canada, J4V 2H1
Cyprus
Recruiting
Nicosia, Cyprus, 2006
Korea, Republic of
Recruiting
Seoul, Korea, Republic of, 120-749
Recruiting
Seoul, Korea, Republic of, 138-736
Recruiting
Seoul, Korea, Republic of, 135-710
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01844674     History of Changes
Other Study ID Numbers: GO28396, 2012-003705-94
Study First Received: April 29, 2013
Last Updated: July 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Tizanidine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anticonvulsants
Muscle Relaxants, Central
Neuromuscular Agents
Parasympatholytics
Autonomic Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014