NCT01849666

Brief Summary

This open-label, multicenter, parallel study will evaluate the effect of multiple doses of vemurafenib on the pharmacokinetics of a single dose of phenprocoumon in patients with BRAFV600 mutation-positive metastatic malignancies. Patients will be randomized to receive either treatment A: a single oral dose of phenprocoumon 6 mg on Day 1 (Eligible patients will have the option to continue treatment with vemurafenib as part of an extension study (NCT01739764).), or treatment B: vemurafenib 960 mg orally twice daily on Days 1-29 plus a single oral dose of phenprocoumon 6 mg on Day 22 (with the option to receive vemurafenib in the extension study after completion of pharmacokinetic assessments).

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Sep 2013

Shorter than P25 for phase_1

Geographic Reach
5 countries

17 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 3, 2013

Completed
5 days until next milestone

First Posted

Study publicly available on registry

May 8, 2013

Completed
4 months until next milestone

Study Start

First participant enrolled

September 1, 2013

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2014

Completed
Last Updated

November 2, 2016

Status Verified

November 1, 2016

Enrollment Period

7 months

First QC Date

May 3, 2013

Last Update Submit

November 1, 2016

Conditions

Malignant Melanoma, Neoplasms

Outcome Measures

Primary Outcomes (5)

  • Pharmacokinetics of single-dose phenprocoumon under conditions of vemurafenib steady-state exposure: Area under the concentration-time curve (AUC)

    Pre-dose and up to 168 hours post-dose

  • Pharmacokinetics of single-dose phenprocoumon under conditions of vemurafenib steady-state exposure: Maximum plasma concentration (Cmax)

    Pre-dose and up to 168 hours post-dose

  • Pharmacokinetics of single-dose phenprocoumon under conditions of vemurafenib steady-state exposure: Time to maximum plasma concentration (Tmax)

    Pre-dose and up to 168 hours post-dose

  • Pharmacokinetics of single-dose phenprocoumon under conditions of vemurafenib steady-state exposure: Terminal half-life (t1/2)

    Pre-dose and up to 168 hours post-dose

  • Pharmacokinetics of single-dose phenprocoumon under conditions of vemurafenib steady-state exposure: Apparent clearance (CL/F)

    Pre-dose and up to 168 hours post-dose

Secondary Outcomes (1)

  • Safety: Incidence, nature and severity of adverse events (AEs) and serious AEs, graded according to NCI CTCAE Version 4.0

    approximately 1.5 years

Study Arms (2)

A: phenprocoumon single dose

ACTIVE COMPARATOR
Drug: phenprocoumon

B: vemurafenib + phenprocoumon single dose

EXPERIMENTAL
Drug: vemurafenib

Interventions

phenprocoumonDRUG

6 mg oral single dose

A: phenprocoumon single dose
vemurafenibDRUG

960 mg bid orally

B: vemurafenib + phenprocoumon single dose

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • History of myocardial infarction within 6 months prior to first dose of study treatment
  • Active central nervous system lesions (i.e. patients with radiographically unstable, symptomatic lesions)
  • History of bleeding or coagulation disorders
  • Allergy or hypersensitivity to vemurafenib or phenprocoumon formulations
  • History of malabsorption or other condition that would interfere with the enteral absorption of study treatment
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (17)

Unknown Facility

Brussels, 1000, Belgium

Location

Unknown Facility

Edegem, 2650, Belgium

Location

Unknown Facility

Ghent, 9000, Belgium

Location

Unknown Facility

Wilrijk, 2610, Belgium

Location

Unknown Facility

Helsinki, 00180, Finland

Location

Unknown Facility

Heidelberg, 69120, Germany

Location

Unknown Facility

Mainz, 55101, Germany

Location

Unknown Facility

Amsterdam, 1066 CX, Netherlands

Location

Unknown Facility

Maastricht, 6229HX, Netherlands

Location

Unknown Facility

Utrecht, 3584 CX, Netherlands

Location

Unknown Facility

Barcelona, Barcelona, 08908, Spain

Location

Unknown Facility

Madrid, Madrid, 280146, Spain

Location

Unknown Facility

Madrid, Madrid, 28031, Spain

Location

Unknown Facility

Madrid, Madrid, 28040, Spain

Location

Unknown Facility

Madrid, Madrid, 28041, Spain

Location

Unknown Facility

Madrid, Madrid, 28050, Spain

Location

Unknown Facility

Pamplona, Navarre, 31008, Spain

Location

MeSH Terms

Conditions

MelanomaNeoplasms

Interventions

PhenprocoumonVemurafenib

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsNeoplasms by SiteSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

4-HydroxycoumarinsCoumarinsBenzopyransPyransHeterocyclic Compounds, 1-RingHeterocyclic CompoundsHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingSulfonamidesAmidesOrganic ChemicalsSulfonesSulfur CompoundsIndoles

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 3, 2013

First Posted

May 8, 2013

Study Start

September 1, 2013

Primary Completion

April 1, 2014

Study Completion

April 1, 2014

Last Updated

November 2, 2016

Record last verified: 2016-11

Locations

ES(7)BE(4)FI(1)DE(2)NL(3)