A Study to Investigate the Effect of Itraconazole and Rifampin on Pharmacokinetics (PK) of Vemurafenib at Steady State

Sponsor

Genentech, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02608034

Collaborator

(none)

Enrollment

Locations

Arm

27.5

Actual Duration (Months)

2.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Melanoma, BRAF V600 Mutation Positive	Drug: Itraconazole Drug: Rifampin Drug: Vemurafenib	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

32 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Two-part, Phase I, Open-label, Multicenter, Two-period, One-sequence Study to Investigate the Effect of Itraconazole and Rifampin on the PK of Vemurafenib at Steady State

Actual Study Start Date :

May 26, 2016

Actual Primary Completion Date :

Sep 10, 2018

Actual Study Completion Date :

Sep 10, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: Vemurafenib+Itraconazole 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: Itraconazole Itraconazole will be administered as a 200 mg oral solution QD during Part 1 only for 20 consecutive days. Drug: Rifampin Rifampin will be administered as a 600 mg oral solution QD during Part 2 only for 20 consecutive days. Drug: Vemurafenib Vemurafenib will be administered in both Part 1 and Part 2 at a dose of 960 mg BID for at least 40 conseutive days.

Arm

Intervention/Treatment

Experimental: Part 1: Vemurafenib+Itraconazole

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: Itraconazole

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

Drug: Rifampin

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

Drug: Vemurafenib

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

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

Incidence of adverse events [28 days after last dose of study treatment (last dose = Day 40)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mary Crowley Medical Research Center	Dallas	Texas	United States	75230
2	Rambam Health Care Campus; Oncology	Haifa		Israel	3109601
3	Hadassah Ein Karem Hospital; Oncology Dept	Jerusalem		Israel	9112000
4	Tel Aviv Sourasky Medical Center; Pharmacy	Tel Aviv		Israel	64239
5	Seoul National University Hospital	Seoul		Korea, Republic of	03080
6	Samsung Medical Center; Gastroenterology	Seoul		Korea, Republic of	135-710
7	Asan Medical Center; Division of Oncology	Seoul		Korea, Republic of	138-736
8	Severance Hospital - Yonsei Uni ; Obstetrics & Gynaecology Dept.	Seoul		Korea, Republic of
9	Republican Clinical Oncologic Dispensary of Republic Of Tatarstan	Kazan		Russian Federation	420029
10	FSBSI "N. N. Blokhin Russian Cancer Research Center"	Moscow		Russian Federation	115478
11	St. Petersburg Oncology Hospital	St Petersburg		Russian Federation	198255

Sponsors and Collaborators

Genentech, Inc.

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Genentech, Inc.

ClinicalTrials.gov Identifier:

NCT02608034

Other Study ID Numbers:

GO29475

First Posted:

Nov 18, 2015

Last Update Posted:

Feb 12, 2020

Last Verified:

Feb 1, 2020

Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 12, 2020