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NCT Number: NCT01844674

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

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Key information

Conditions

Malignant Melanoma, Neoplasms Melanoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Hospital de Caridade de Ijui; Oncologia, Ijuí, Rio Grande do Sul, Brazil

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adults 18 to 70 years of age, inclusive
  • 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 greater than or equal to (>/=) 12 weeks
  • Participant has not consumed tobacco or nicotine-containing products for 42 days 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
  • 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 (participants with radiographically unstable, symptomatic lesions)
  • Participants with CYP1A2 gene mutation (-3113G->A), either in one or two alleles
  • 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 human immunodeficiency (HIV) infection requiring antiretroviral treatment, acquired immune deficiency syndrome (AIDS)-related illness, or active hepatitis B or C
  • Pregnant or breastfeeding women

Treatment and study plan

Tizanidine

Drug

Participants will receive tizanidine as single oral doses, 2 milligrams (mg) on Day 1 and repeated on Day 22, each following an overnight fast >/= 10 hours.

Vemurafenib

Drug

Participants will receive vemurafenib as multiple oral doses, 960 mg twice daily on Days 2 to 22.

Primary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

Secondary outcomes

  1. Safety: Incidence, nature and severity of adverse events and serious adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0

    Time frame: Up to approximately 9 months

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study title

A Phase I, Open-Label, Multicenter, 3- Period, Fixed-Sequence Study to Investigate the Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Tizanidine (a CYP1A2 Substrate) in Patients With BRAFV600 Mutation-Positive Metastatic Malignancy

Important dates

Study start
2013
Primary completion
2014
Study completion
2014
First posted
May 1, 2013
Registry last updated
Mar 20, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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