Back to resultsA Study to Investigate the Effect of Itraconazole and Rifampin on Pharmacokinetics (PK) of Vemurafenib at Steady State
Primary Purpose
Metastatic Melanoma, BRAF V600 Mutation Positive
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Itraconazole
Rifampin
Vemurafenib
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Melanoma, BRAF V600 Mutation Positive
Eligibility Criteria
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.
Sites / Locations
- Mary Crowley Medical Research Center
- Rambam Health Care Campus; Oncology
- Hadassah Ein Karem Hospital; Oncology Dept
- Tel Aviv Sourasky Medical Center; Pharmacy
- Seoul National University Hospital
- Samsung Medical Center; Gastroenterology
- Asan Medical Center; Division of Oncology
- Severance Hospital - Yonsei Uni ; Obstetrics & Gynaecology Dept.
- Republican Clinical Oncologic Dispensary of Republic Of Tatarstan
- FSBSI "N. N. Blokhin Russian Cancer Research Center"
- St. Petersburg Oncology Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Part 1: Vemurafenib+Itraconazole
Arm Description
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).
Outcomes
Primary Outcome Measures
Area under the concentration-time curve From Time 0 to 12 Hours Postdose (AUC0-12)
Maximum observed concentration (Cmax)
Time to maximum concentration (Tmax)
Secondary Outcome Measures
Incidence of adverse events
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02608034
Brief Title
A Study to Investigate the Effect of Itraconazole and Rifampin on Pharmacokinetics (PK) of Vemurafenib at Steady State
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
May 26, 2016 (Actual)
Primary Completion Date
September 10, 2018 (Actual)
Study Completion Date
September 10, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
4. Oversight
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Melanoma, BRAF V600 Mutation Positive
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Part 1: Vemurafenib+Itraconazole
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Itraconazole
Intervention Description
Itraconazole will be administered as a 200 mg oral solution QD during Part 1 only for 20 consecutive days.
Intervention Type
Drug
Intervention Name(s)
Rifampin
Intervention Description
Rifampin will be administered as a 600 mg oral solution QD during Part 2 only for 20 consecutive days.
Intervention Type
Drug
Intervention Name(s)
Vemurafenib
Intervention Description
Vemurafenib will be administered in both Part 1 and Part 2 at a dose of 960 mg BID for at least 40 conseutive days.
Primary Outcome Measure Information:
Title
Area under the concentration-time curve From Time 0 to 12 Hours Postdose (AUC0-12)
Time Frame
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
Title
Maximum observed concentration (Cmax)
Time Frame
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
Title
Time to maximum concentration (Tmax)
Time Frame
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 Measure Information:
Title
Incidence of adverse events
Time Frame
28 days after last dose of study treatment (last dose = Day 40)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Mary Crowley Medical Research Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
Rambam Health Care Campus; Oncology
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Facility Name
Hadassah Ein Karem Hospital; Oncology Dept
City
Jerusalem
ZIP/Postal Code
9112000
Country
Israel
Facility Name
Tel Aviv Sourasky Medical Center; Pharmacy
City
Tel Aviv
ZIP/Postal Code
64239
Country
Israel
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Samsung Medical Center; Gastroenterology
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
Facility Name
Asan Medical Center; Division of Oncology
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of
Facility Name
Severance Hospital - Yonsei Uni ; Obstetrics & Gynaecology Dept.
City
Seoul
Country
Korea, Republic of
Facility Name
Republican Clinical Oncologic Dispensary of Republic Of Tatarstan
City
Kazan
ZIP/Postal Code
420029
Country
Russian Federation
Facility Name
FSBSI "N. N. Blokhin Russian Cancer Research Center"
City
Moscow
ZIP/Postal Code
115478
Country
Russian Federation
Facility Name
St. Petersburg Oncology Hospital
City
St Petersburg
ZIP/Postal Code
198255
Country
Russian Federation
12. IPD Sharing Statement
Learn more about this trial
A Study to Investigate the Effect of Itraconazole and Rifampin on Pharmacokinetics (PK) of Vemurafenib at Steady State
We'll reach out to this number within 24 hrs