Malignant Melanoma, NeoplasmsPhase 1NCT01844674
A Study on the Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Tizanidine in Patients With BRAFV600 Mutation-Positive Metastatic Malignancies
A Phase 1 study testing Tizanidine and Vemurafenib in people with Malignant Melanoma, Neoplasms, run by Hoffmann-La Roche at 12 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Malignant Melanoma, Neoplasms
- What is being tested?
- Tizanidine and Vemurafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 12 sitesin 5 countries
- Study dates
- 2 Sep 2013to 26 Aug 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
12 sites in 5 countries.
12 sites in 5 countries
Brazil4 sites
Hospital de Caridade de Ijui; Oncologia
Ijuí, Rio Grande do Sul, 98700-000
CITO - Centro Integrado de Terapia Onco-Hematológica - Hospital da Cidade de Passo Fundo
Passo Fundo, Rio Grande do Sul, 99010-260
Hospital Sao Lucas - PUCRS
Porto Alegre, Rio Grande do Sul, 90610-000
Instituto Nacional do Cancer - INCA
Rio de Janeiro, Rio de Janeiro, 20560-120
United States3 sites
Karmanos Cancer Center
Detroit, Michigan, 48201
Duke University Health Systems
Durham, North Carolina, 27710
Diablo Valley Oncology and Hematology
Pleasant Hill, California, 94523
South Korea3 sites
Severance Hospital, Yonsei University Health System
Seoul, 03722
Samsung Medical Center
Seoul, 06351
Asan Medical Center.
Seoul, 138-736
Canada1 site
CSSS champlain - Charles-Le Moyne
Greenfield Park, Quebec, J4V 2H1
About this study
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
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).
- Conditions
- Malignant Melanoma, Neoplasms
- Being tested
- Tizanidine, Vemurafenib
- Medical subject headings
- Melanoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TizanidineDrug
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.
VemurafenibDrug
Participants will receive vemurafenib as multiple oral doses, 960 mg twice daily on Days 2 to 22.
| Study group | Role | What they receive |
|---|---|---|
| Pharmacokinetic Population | Experimental | 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. Receives: Drug: Tizanidine; Drug: Vemurafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Area under the concentration-time curve (AUC)
Measured: Pre-dose and up to 12 hours post-dose
Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Maximum plasma concentration (Cmax)
Measured: Pre-dose and up to 12 hours post-dose
Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Time to maximum plasma concentration (Tmax)
Measured: Pre-dose and up to 12 hours post-dose
Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Terminal half-life (t1/2)
Measured: Pre-dose and up to 12 hours post-dose
Pharmacokinetics of tizanidine under conditions of vemurafenib steady-state exposure: Apparent clearance (CL/F)
Measured: 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
Measured: Up to approximately 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2013 (estimated)
- Study start2 Sep 2013
- Primary completion26 Aug 2014
- Study completion26 Aug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant Melanoma, NeoplasmsStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01844674
- Sponsor's protocol ID
- GO28396
- Other IDs
- 2012-003705-94
- Status last verified
- Mar 2017
- First submitted
- 29 Apr 2013
- Last updated
- 20 Mar 2017
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01844674
- Acronym / sponsor ID
- GO28396
- Conditions
- Malignant Melanoma, Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 2 Sep 2013 (actual)
- Primary completion
- 26 Aug 2014 (actual)
- Study completion
- 26 Aug 2014 (actual)
- First posted
- 1 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pharmacokinetic Population | Experimental | Drug: Tizanidine, Drug: VemurafenibAll 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TizanidineParticipants 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. | Drug | Pharmacokinetic Population |
| VemurafenibParticipants will receive vemurafenib as multiple oral doses, 960 mg twice daily on Days 2 to 22. | Drug | Pharmacokinetic Population |
Primary outcome
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
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
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
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
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
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
12 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tizanidine and Vemurafenib in people with Malignant Melanoma, Neoplasms, run by Hoffmann-La Roche at 12 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Brazil, United States, South Korea, Canada, Cyprus. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2017.