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

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Melanoma, BRAF V600 Mutation Positive
• Intervention / Treatment: Drug: Itraconazole; Drug: Rifampin; Drug: Vemurafenib

• Study Type: Interventional
• Enrollment (Anticipated): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
Incidence of adverse events	28 days after last dose of study treatment (last dose = Day 40)

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2016
• Primary Completion (Actual): September 10, 2018
• Study Completion (Actual): September 10, 2018

Study Registration Dates

• First Submitted: November 3, 2015
• First Submitted That Met QC Criteria: November 16, 2015
• First Posted (Estimate): November 18, 2015

Study Record Updates

• Last Update Posted (Actual): February 12, 2020
• Last Update Submitted That Met QC Criteria: February 11, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Bacterial Agents; Protein Kinase Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Hormone Antagonists; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Steroid Synthesis Inhibitors; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; 14-alpha Demethylase Inhibitors; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rifampin; Itraconazole; Vemurafenib
• Other Study ID Numbers: GO29475