Malignant Melanoma, NeoplasmsPhase 1NCT01851824
A Study of the Effect of Vemurafenib on the Pharmacokinetics of Acenocoumarol in Patients With BRAFV600 Mutation-Positive Metastatic Malignancy
A Phase 1 study testing acenocoumarol and vemurafenib in people with Malignant Melanoma, Neoplasms, run by Hoffmann-La Roche at 20 sites in 9 countries.
Trial summary
This open-label, multicenter, 3-period, fixed-sequence study will evaluate the effect of multiple doses of vemurafenib on the pharmacokinetics of a single dose of acenocoumarol 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?
- acenocoumarol and vemurafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 20 sitesin 9 countries
- Study dates
- Aug 2013to Jun 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
- Adult patients, 18-70 years of age
- Patients with either unresectable Stage IIIc or IV BRAFV600 mutation-positive metastatic melanoma or other malignant BRAFV600 mutation-positive tumor type and who have no acceptable standard treatment options
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- Full recovery from any major surgery or significant traumatic injury at least 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 female partners of childbearing potential must agree to use 2 effective methods of contraception as defined by protocol during the course of the study and for at least 6 months after completion of study treatment
Who cannot join
- Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of Day 1
- Prior anti-cancer therapy within 28 days (6 weeks for nitrosureas or mitocyn C, or 14 days for hormonal therapy or kinase inhibitors) before the first dose of study treatment Day 1
- Palliative radiotherapy within 2 weeks prior to first dose of study treatment Day 1
- Experimental therapy within 4 weeks prior to first dose of study treatment Day 1
- History of clinically significant cardiac or pulmonary dysfunction, including current uncontrolled Grade >/=2 hypertension or unstable angina
- Current Grade >/=2 dyspnea or hypoxia or need for oxygen supplementation
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- History of myocardial infarction within 6 months prior to first dose of study treatment
- Active central nervous system lesions (i.e. participants with radiographically unstable, symptomatic lesions)
- History of bleeding or coagulation disorders
- Allergy or hypersensitivity to vemurafenib or acenocoumarol formulations
- History of malabsorption or other condition that would interfere with the enteral absorption of study treatment
- Participants with VKORC1 mutations (1639G\→A, 1173C\→T) in either one allele (heterozygous)or two alleles (homozygous)
- Participants with CYP2C9*3 mutations in either one allele (heterozygous) or two alleles (homozygous)
- History of clinically significant liver disease (including cirrhosis), current alcohol abuse, or active hepatitis B or hepatitis C virus infection
- Human immunodeficiency virus (HIV) infection requiring antiretroviral treatment, or AIDS-related illness
- Pregnant or lactating women
Trial locations and contacts
20 sites in 9 countries.
20 sites in 9 countries
Spain5 sites
Study site
Barcelona, Barcelona, 08036
Study site
Barcelona, Barcelona, 08908
Study site
Madrid, Madrid, 28031
Study site
Madrid, Madrid, 28040
Study site
Madrid, Madrid, 28050
Germany3 sites
Study site
Buxtehude, 21614
Study site
Essen, 45122
Study site
Mannheim, 68167
Netherlands3 sites
Study site
Amsterdam, 1066 CX
Study site
Maastricht, 6229HX
Study site
Utrecht, 3584 CX
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 ORAL DOSE OF ACENOCOUMAROL IN PATIENTS WITH BRAFV600 MUTATION-POSITIVE METASTATIC MALIGNANCY
This open-label, multicenter, 3-period, fixed-sequence study will evaluate the effect of multiple doses of vemurafenib on the pharmacokinetics of a single dose of acenocoumarol in participants with BRAFV600 mutation-positive metastatic malignancies. Participants will receive a single dose of acenocoumarol 4 mg orally on Day 1 and Day 23, vemurafenib 960 mg orally twice daily on Days 4-26. After completion of pharmacokinetic assessments on Day 26, eligible participants will have the option to continue treatment with vemurafenib as part of an extension study (GO28399 [NCT01739764]).
- Conditions
- Malignant Melanoma, Neoplasms
- Being tested
- acenocoumarol, 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.
acenocoumarolDrug
4 mg single oral doses on Days 1 and 23
vemurafenibDrug
Also called Zelboraf
960 mg orally bid, 20 days (Days 4-23)
| Study group | Role | What they receive |
|---|---|---|
| Acenocoumarol + Vemurafenib | Experimental | Not described Receives: Drug: acenocoumarol; Drug: vemurafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Area under the concentration-time curve (AUC)
Measured: Pre-dose and up to 72 hours post-dose
Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Maximum plasma concentration (Cmax)
Measured: Pre-dose and up to 72 hours post-dose
Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Time to maximum plasma concentration (Tmax)
Measured: Pre-dose and up to 72 hours post-dose
Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Terminal half-life (t1/2)
Measured: Pre-dose and up to 72 hours post-dose
Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Apparent clearance (CL/F)
Measured: Pre-dose and up to 72 hours post-dose
Secondary outcomes (1)
Safety: Incidence of Adverse Events and Serious Adverse Events
Measured: approximately 1.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2013 (estimated)
- Study startAug 2013
- Primary completionJun 2014
- Study completionJun 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
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 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
- NCT01851824
- Sponsor's protocol ID
- GO28397
- Other IDs
- 2012-003706-27
- Status last verified
- Nov 2016
- First submitted
- 3 May 2013
- Last updated
- 2 Nov 2016
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2016. 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 ORAL DOSE OF ACENOCOUMAROL IN PATIENTS WITH BRAFV600 MUTATION-POSITIVE METASTATIC MALIGNANCY
- ClinicalTrials.gov ID
- NCT01851824
- Acronym / sponsor ID
- GO28397
- Conditions
- Malignant Melanoma, Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- Aug 2013
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 13 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 doses of vemurafenib on the pharmacokinetics of a single dose of acenocoumarol in participants with BRAFV600 mutation-positive metastatic malignancies. Participants will receive a single dose of acenocoumarol 4 mg orally on Day 1 and Day 23, vemurafenib 960 mg orally twice daily on Days 4-26. After completion of pharmacokinetic assessments on Day 26, eligible participants will have the option to continue treatment with vemurafenib as part of an extension study (GO28399 [NCT01739764]).
Study design
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Acenocoumarol + Vemurafenib | Experimental | Drug: acenocoumarol, Drug: vemurafenib |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Adult patients, 18-70 years of age
- Patients with either unresectable Stage IIIc or IV BRAFV600 mutation-positive metastatic melanoma or other malignant BRAFV600 mutation-positive tumor type and who have no acceptable standard treatment options
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- Full recovery from any major surgery or significant traumatic injury at least 14 days prior to the first dose of study treatment
- Adequate hematologic and end organ function
Key exclusion criteria (16 listed)
- Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of Day 1
- Prior anti-cancer therapy within 28 days (6 weeks for nitrosureas or mitocyn C, or 14 days for hormonal therapy or kinase inhibitors) before the first dose of study treatment Day 1
- Palliative radiotherapy within 2 weeks prior to first dose of study treatment Day 1
- Experimental therapy within 4 weeks prior to first dose of study treatment Day 1
- History of clinically significant cardiac or pulmonary dysfunction, including current uncontrolled Grade >/=2 hypertension or unstable angina
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 |
|---|---|---|
| acenocoumarol4 mg single oral doses on Days 1 and 23 | Drug | Acenocoumarol + Vemurafenib |
| vemurafenibAlso: Zelboraf960 mg orally bid, 20 days (Days 4-23) | Drug | Acenocoumarol + Vemurafenib |
Primary outcome
Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Area under the concentration-time curve (AUC)
Time frame: Pre-dose and up to 72 hours post-dose
Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Maximum plasma concentration (Cmax)
Time frame: Pre-dose and up to 72 hours post-dose
Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Time to maximum plasma concentration (Tmax)
Time frame: Pre-dose and up to 72 hours post-dose
Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Terminal half-life (t1/2)
Time frame: Pre-dose and up to 72 hours post-dose
Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Apparent clearance (CL/F)
Time frame: Pre-dose and up to 72 hours post-dose
1 secondary outcome
Safety: Incidence of Adverse Events and Serious Adverse Events
Time frame: approximately 1.5 years
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 2 Nov 2016.
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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
20 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing acenocoumarol and vemurafenib in people with Malignant Melanoma, Neoplasms, run by Hoffmann-La Roche at 20 sites in 9 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 16 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 2 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Spain, Germany, Netherlands, Greece, New Zealand and 4 more countries. 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 single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Area under the concentration-time curve (AUC) (time frame: Pre-dose and up to 72 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 2 Nov 2016.