NCT01765543

Brief Summary

This open-label, multi-center, three-period, one-sequence study will investigate the effect of rifampin on the PK of vemurafenib in participants with unresectable BRAFV600-mutation positive metastatic melanoma or other malignant tumor type that harbors a V600-activating mutation of BRAF without acceptable standard treatment options. Eligible participants will have the option to continue treatment with vemurafenib as part of an extension study GO28399 (NCT01739764).

Trial Health

93
On Track

Trial Health Score

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

Enrollment
27

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Jul 2013

Typical duration for phase_1

Geographic Reach
5 countries

15 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

January 9, 2013

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 10, 2013

Completed
6 months until next milestone

Study Start

First participant enrolled

July 1, 2013

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2015

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

December 15, 2016

Completed
Last Updated

December 15, 2016

Status Verified

October 1, 2016

Enrollment Period

2.3 years

First QC Date

January 9, 2013

Results QC Date

October 21, 2016

Last Update Submit

October 21, 2016

Conditions

Malignant Melanoma, Neoplasms

Outcome Measures

Primary Outcomes (3)

  • Area Under the Plasma Concentration Time-curve From Zero to the Last Measurable Concentration Time Point (AUClast) of Vemurafenib

    AUClast is the area under the vemurafenib plasma concentration versus time curve from time zero to the time of last measured concentration of vemurafenib (Tlast). Area under the curve (AUC) is a measure of the plasma concentration of a drug over time. AUClast is presented in micrograms times (\*) hour per milliliter (mcg\*h/mL).

    Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)

  • Area Under the Plasma Concentration Time-curve From Zero to Extrapolated Infinite Time (AUC[0-inf]) of Vemurafenib

    AUC(0-inf) is the AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). AUC is a measure of the plasma concentration of a drug over time. AUC(0-inf) is presented in mcg\*h/mL.

    Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)

  • Maximum Observed Plasma Concentration (Cmax) of Vemurafenib

    Cmax is the maximum observed plasma vemurafenib concentration, presented in microgram per milliliter (mcg/mL).

    Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)

Other Outcomes (5)

  • Time to Reach Cmax (Tmax) of Vemurafenib

    Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)

  • Plasma Elimination Half Life (t1/2) of Vemurafenib

    Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)

  • Plasma Apparent Clearance (CL/F) of Vemurafenib

    Predose (0 hour), 1, 2, 4, 6, 8, 12, 24, 30-32, 48, 72, 96, 120, 168 hours post vemurafenib-dose on Day 1 (Period A) and Day 17 (Period C)

  • +2 more other outcomes

Study Arms (1)

Vemurafenib + Rifampin

EXPERIMENTAL

There will be 3 intervention periods in the study: Period A (Days 1 to 7), Period B (Days 8 to 16), and Period C (Days 17 to 24). Participants, after an overnight fast of at least 10 hours, will receive vemurafenib at a dose of 960 milligrams (mg) as film-coated tablets orally alone on Day 1 (Period A); with rifampin (at a dose of 600 mg as capsules orally) on Day 17 (Period C); and rifampin alone at a dose of 600 mg as capsules orally once daily will be administered from Days 8 through 16 (Period B) and from Days 18 through 23 (Period C).

Drug: RifampinDrug: Vemurafenib

Interventions

RifampinDRUG

Rifampin at a dose of 600 mg as capsules orally once daily will be administered from Days 8 through 23 (Periods B and C).

Vemurafenib + Rifampin
VemurafenibDRUG

Participants, after an overnight fast of at least 10 hours, will receive vemurafenib at a dose of 960 mg as film-coated tablets orally on Day 1 (Period A) and on Day 17 (Period C).

Also known as: RO5185426, Zelboraf
Vemurafenib + Rifampin

Eligibility Criteria

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

You may qualify if:

  • Participants with either unresectable Stage IIIc or Stage IV metastatic melanoma positive for the BRAF V600 mutation or other malignant tumor type that harbors a V600-activating mutation of BRAF, as determined by results of cobas® 4800 BRAF V600 mutation test or a Deoxyribonucleic acid (DNA) sequencing method, and who have no acceptable standard treatment options
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
  • Life expectancy of greater than or equal to (\>/=) 12 weeks
  • Full recovery from the effects of any major surgery or significant traumatic injury within 14 days prior to the first dose of study treatment
  • Adequate hematologic and end organ function
  • Female participants of childbearing potential and male participants with partners of childbearing potential must agree to always use 2 effective methods of contraception
  • Negative serum pregnancy test within 7 days prior to commencement of dosing in women of childbearing potential

You may not qualify if:

  • Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of first dose of study drug
  • Requirement for immediate or urgent treatment with daily vemurafenib and for whom the intermittent schedule of vemurafenib employed during the 24-day period for this trial is not clinically acceptable
  • Allergy or hypersensitivity to components of the vemurafenib formulation
  • Experimental therapy within 4 weeks prior to first dose of study drug
  • Major surgical procedure or significant traumatic injury within 14 days prior to first dose of study drug, or anticipation of the need for major surgery during study treatment
  • Prior anti-cancer therapy within 28 days before the first dose of study drug
  • History of clinically significant cardiac or pulmonary dysfunction
  • History of symptomatic congestive heart failure of any New York Heart Association class or serious cardiac arrhythmia requiring treatment
  • History of myocardial infarction within 6 months prior to first dose of study drug
  • Current dyspnea at rest, owing to complications of advanced malignancy or any requirement for supplemental oxygen to perform activities of daily living
  • History of congenital long QT syndrome or corrected QT interval (QTc) greater than (\>) 450 milliseconds
  • Active central nervous system lesions
  • Uncontrolled or poorly controlled diabetes
  • Current severe, uncontrolled systemic disease

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

Unknown Facility

Rogers, Arkansas, 72758, United States

Location

Unknown Facility

Pleasant Hill, California, 94523, United States

Location

Unknown Facility

Middletown, Ohio, 45042, United States

Location

Unknown Facility

Dallas, Texas, 75246, United States

Location

Unknown Facility

Porto Alegre, Rio Grande do Sul, 90020-090, Brazil

Location

Unknown Facility

Porto Alegre, Rio Grande do Sul, 90035-003, Brazil

Location

Unknown Facility

Porto Alegre, Rio Grande do Sul, 90840-440, Brazil

Location

Unknown Facility

Varaždin, 42000, Croatia

Location

Unknown Facility

Zagreb, 10000, Croatia

Location

Unknown Facility

Alexandria, 21131, Egypt

Location

Unknown Facility

Cairo, 11796, Egypt

Location

Unknown Facility

Dakahlia, 324, Egypt

Location

Unknown Facility

Tanta, Egypt

Location

Unknown Facility

Cape Town, 7570, South Africa

Location

Unknown Facility

Port Elizabeth, 6045, South Africa

Location

MeSH Terms

Conditions

MelanomaNeoplasms

Interventions

RifampinVemurafenib

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)

RifamycinsHeterocyclic Compounds, 4 or More RingsHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsLactams, MacrocyclicMacrocyclic CompoundsPolycyclic CompoundsSulfonamidesAmidesOrganic ChemicalsSulfonesSulfur CompoundsIndolesHeterocyclic Compounds, 2-Ring

Results Point of Contact

Title
Medical Communications
Organization
Hoffmann-La Roche
genentech@druginfo.com
800-821-8590

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 9, 2013

First Posted

January 10, 2013

Study Start

July 1, 2013

Primary Completion

November 1, 2015

Study Completion

November 1, 2015

Last Updated

December 15, 2016

Results First Posted

December 15, 2016

Record last verified: 2016-10

Locations

ZA(2)EG(4)US(4)CR(2)BR(3)