NCT02608034

Brief Summary

This is a two-part, Phase 1, open-label, multicenter, two-period, one-sequence study to investigate the effect of itraconazole and rifampin on the PK of vemurafenib following multiple 960 milligrams (mg) twice daily (BID) dosing in adult participants with unresectable Stage IIIC or Stage IV metastatic melanoma positive for the BRAF V600 mutation, or other malignant tumor types that harbor a V600-activating mutation of BRAF where the participant has no acceptable standard treatment options.

Trial Health

90
On Track

Trial Health Score

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

Enrollment
32

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started May 2016

Typical duration for phase_1

Geographic Reach
4 countries

11 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

November 3, 2015

Completed
15 days until next milestone

First Posted

Study publicly available on registry

November 18, 2015

Completed
6 months until next milestone

Study Start

First participant enrolled

May 26, 2016

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 10, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 10, 2018

Completed
Last Updated

February 12, 2020

Status Verified

February 1, 2020

Enrollment Period

2.3 years

First QC Date

November 3, 2015

Last Update Submit

February 11, 2020

Conditions

Metastatic Melanoma, BRAF V600 Mutation Positive

Outcome Measures

Primary Outcomes (3)

  • Area under the concentration-time curve From Time 0 to 12 Hours Postdose (AUC0-12)

    Period A and B: Pre-morning dose on Day 18, 19, and 20 and 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose on Day 20

  • Maximum observed concentration (Cmax)

    Period A and B: Pre-morning dose on Day 18, 19, and 20 and 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose on Day 20

  • Time to maximum concentration (Tmax)

    Period A and B: Pre-morning dose on Day 18, 19, and 20 and 1, 2, 3, 4, 6, 8, and 12 hours post-morning dose on Day 20

Secondary Outcomes (1)

  • Incidence of adverse events

    28 days after last dose of study treatment (last dose = Day 40)

Study Arms (1)

Part 1: Vemurafenib+Itraconazole

EXPERIMENTAL

Part 1: Participants will receive vemurafenib orally BID up to Day 20 (Period A) followed by vemurafenib orally BID along with itraconazole orally once in the morning from Days 21 to 40 (Period B).\\nPart 2: Participants will receive vemurafenib orally BID up to Day 20 (Period A) followed by vemurafenib orally BID along with rifampin orally once in the morning from Days 21 to 40 (Period B).

Drug: ItraconazoleDrug: RifampinDrug: Vemurafenib

Interventions

ItraconazoleDRUG

Itraconazole will be administered as a 200 mg oral solution QD during Part 1 only for 20 consecutive days.

Part 1: Vemurafenib+Itraconazole
RifampinDRUG

Rifampin will be administered as a 600 mg oral solution QD during Part 2 only for 20 consecutive days.

Part 1: Vemurafenib+Itraconazole
VemurafenibDRUG

Vemurafenib will be administered in both Part 1 and Part 2 at a dose of 960 mg BID for at least 40 conseutive days.

Part 1: Vemurafenib+Itraconazole

Eligibility Criteria

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

You may qualify if:

  • Participants with age greater than or equal to (\>=) 18 years with either unresectable Stage IIIC or Stage IV metastatic melanoma positive for the BRAF V600 mutation, or other malignant tumor types that harbor a V600-activating mutation of BRAF
  • Eastern Cooperative Oncology Group Performance Status 0 to 2
  • Life expectancy \>=12 weeks
  • Adequate hematologic and end organ function obtained within 2 weeks prior to first dose of study drug
  • Female participants of childbearing potential and male participants with partners of childbearing potential must agree to always use two effective methods of contraception including at least one method with a failure rate of \<1% per year during the course of the study and for at least 6 months after completion of study treatment
  • Negative serum pregnancy test within 7 days prior to commencement of dosing in women of childbearing potential
  • Absence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

You may not qualify if:

  • Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of Study Day 1 of Period A
  • Allergy or hypersensitivity to components of the vemurafenib formulation
  • Experimental therapy within 4 weeks prior to first dose of study drug treatment on Study Day 1 of Period A
  • Major surgical procedure or significant traumatic injury within 14 days prior to first dose of study drug treatment on Study Day 1 of Period A, or anticipation of the need for major surgery during study treatment
  • Prior anti-cancer therapy (e.g., biologic or other targeted therapy, chemotherapy) within 28 days (6 weeks for nitrosoureas or mitomycin C, and 14 days for hormonal therapy or kinase inhibitors) before the first dose of study treatment on Study Day 1 of Period A.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

Mary Crowley Medical Research Center

Dallas, Texas, 75230, United States

Location

Rambam Health Care Campus; Oncology

Haifa, 3109601, Israel

Location

Hadassah Ein Karem Hospital; Oncology Dept

Jerusalem, 9112000, Israel

Location

Tel Aviv Sourasky Medical Center; Pharmacy

Tel Aviv, 64239, Israel

Location

Republican Clinical Oncologic Dispensary of Republic Of Tatarstan

Kazan', 420029, Russia

Location

FSBSI "N. N. Blokhin Russian Cancer Research Center"

Moscow, 115478, Russia

Location

St. Petersburg Oncology Hospital

Saint Petersburg, 198255, Russia

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Samsung Medical Center; Gastroenterology

Seoul, 135-710, South Korea

Location

Asan Medical Center; Division of Oncology

Seoul, 138-736, South Korea

Location

Severance Hospital - Yonsei Uni ; Obstetrics & Gynaecology Dept.

Seoul, South Korea

Location

MeSH Terms

Conditions

Melanoma

Interventions

ItraconazoleRifampinVemurafenib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

TriazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPiperazinesRifamycinsHeterocyclic Compounds, 4 or More RingsHeterocyclic Compounds, Fused-RingLactams, MacrocyclicMacrocyclic CompoundsPolycyclic CompoundsSulfonamidesAmidesOrganic ChemicalsSulfonesSulfur CompoundsIndolesHeterocyclic Compounds, 2-Ring

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR

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

November 3, 2015

First Posted

November 18, 2015

Study Start

May 26, 2016

Primary Completion

September 10, 2018

Study Completion

September 10, 2018

Last Updated

February 12, 2020

Record last verified: 2020-02

Locations

RU(3)KR(4)US(1)IL(3)