Back to resultsA Study on the Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Tizanidine in Patients With BRAFV600 Mutation-Positive Metastatic Malignancies
Primary Purpose
Malignant Melanoma, Neoplasms
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Tizanidine
Vemurafenib
Sponsored by
About this trial
This is an interventional other trial for Malignant Melanoma, Neoplasms
Eligibility Criteria
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
Sites / Locations
- Diablo Valley Oncology and Hematology
- Karmanos Cancer Center
- Duke University Health Systems
- Instituto Nacional do Cancer - INCA
- Hospital de Caridade de Ijui; Oncologia
- CITO - Centro Integrado de Terapia Onco-Hematológica - Hospital da Cidade de Passo Fundo
- Hospital Sao Lucas - PUCRS
- CSSS champlain - Charles-Le Moyne
- Bank of Cyprus Oncology Center
- Severance Hospital, Yonsei University Health System
- Samsung Medical Center
- Asan Medical Center.
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Pharmacokinetic Population
Arm Description
All participants will receive a 3-period treatment including single-dose tizanidine on Day 1, twice-daily vemurafenib on Days 2 to 21, and both agents together on Day 22.
Outcomes
Primary Outcome Measures
Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Area under the concentration-time curve (AUC)
Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Maximum plasma concentration (Cmax)
Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Time to maximum plasma concentration (Tmax)
Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Terminal half-life (t1/2)
Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Apparent clearance (CL/F)
Secondary Outcome Measures
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01844674
Brief Title
A Study on the Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Tizanidine in Patients With BRAFV600 Mutation-Positive Metastatic Malignancies
Official 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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
September 2, 2013 (Actual)
Primary Completion Date
August 26, 2014 (Actual)
Study Completion Date
August 26, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
Brief Summary
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Melanoma, Neoplasms
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pharmacokinetic Population
Arm Type
Experimental
Arm Description
All participants will receive a 3-period treatment including single-dose tizanidine on Day 1, twice-daily vemurafenib on Days 2 to 21, and both agents together on Day 22.
Intervention Type
Drug
Intervention Name(s)
Tizanidine
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Vemurafenib
Intervention Description
Participants will receive vemurafenib as multiple oral doses, 960 mg twice daily on Days 2 to 22.
Primary Outcome Measure Information:
Title
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
Title
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
Title
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
Title
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
Title
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 Outcome Measure Information:
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Diablo Valley Oncology and Hematology
City
Pleasant Hill
State/Province
California
ZIP/Postal Code
94523
Country
United States
Facility Name
Karmanos Cancer Center
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Duke University Health Systems
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Instituto Nacional do Cancer - INCA
City
Rio de Janeiro
State/Province
RJ
ZIP/Postal Code
20560-120
Country
Brazil
Facility Name
Hospital de Caridade de Ijui; Oncologia
City
Ijui
State/Province
RS
ZIP/Postal Code
98700-000
Country
Brazil
Facility Name
CITO - Centro Integrado de Terapia Onco-Hematológica - Hospital da Cidade de Passo Fundo
City
Passo Fundo
State/Province
RS
ZIP/Postal Code
99010-260
Country
Brazil
Facility Name
Hospital Sao Lucas - PUCRS
City
Porto Alegre
State/Province
RS
ZIP/Postal Code
90610-000
Country
Brazil
Facility Name
CSSS champlain - Charles-Le Moyne
City
Greenfield Park
State/Province
Quebec
ZIP/Postal Code
J4V 2H1
Country
Canada
Facility Name
Bank of Cyprus Oncology Center
City
Nicosia
ZIP/Postal Code
2006
Country
Cyprus
Facility Name
Severance Hospital, Yonsei University Health System
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Asan Medical Center.
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of
12. IPD Sharing Statement
Learn more about this trial
A Study on the Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Tizanidine in Patients With BRAFV600 Mutation-Positive Metastatic Malignancies
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