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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01767623




Registration number
NCT01767623
Ethics application status
Date submitted
11/01/2013
Date registered
14/01/2013
Date last updated
13/02/2018

Titles & IDs
Public title
A Study of The Impact of Severe Hepatic Impairment on the Pharmacokinetics and Safety of Vemurafenib in BRAF V600 Mutation-Positive Cancer Participants
Scientific title
An Open Label, Phase I Study to Evaluate the Impact of Severe Hepatic Impairment on the Pharmacokinetics and Safety of Vemurafenib in BRAF V600 Mutation Positive Cancer Patients
Secondary ID [1] 0 0
2012-003820-18
Secondary ID [2] 0 0
GO28053
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Vemurafenib

Active Comparator: Cohort 1: Participants with Normal Liver Function - Participants with normal liver function (according to National Cancer Institute [NCI] liver dysfunction criteria) will receive vemurafenib 960 mg BID from Day 1 until the morning dose on Day 20 and then from Day 27 onward until disease progression, safety-related treatment termination, withdrawal of consent, death, or a decision by the Sponsor to terminate the study, whichever occurs first.

Experimental: Cohort 2: Participants with Severe Liver Dysfunction - Participants with severe liver dysfunction (according to NCI liver dysfunction criteria) will receive vemurafenib 720 mg BID from Day 1 until the morning dose on Day 20 and then from Day 27 onward until disease progression, safety-related treatment termination, withdrawal of consent, death, or a decision by the Sponsor to terminate the study, whichever occurs first.


Treatment: Drugs: Vemurafenib
Vemurafenib orally BID 960 or 720 mg.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose-Normalized Area Under the Concentration-Time Curve (AUC) of Vemurafenib During the Dose Interval (12 hours) (AUCtau) on Day 20
Timepoint [1] 0 0
Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose on Day 20
Primary outcome [2] 0 0
Dose-Normalized Maximum Observed Concentration (Cmax) of Vemurafenib on Day 20
Timepoint [2] 0 0
Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose on Day 20
Secondary outcome [1] 0 0
Percentage of Participants with Adverse Events (AEs)
Timepoint [1] 0 0
Baseline up to approximately 3 years
Secondary outcome [2] 0 0
Dose-Normalized AUCtau of of Vemurafenib on Day 1
Timepoint [2] 0 0
Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose on Day 1
Secondary outcome [3] 0 0
Dose-Normalized AUC from Time 0 to Last Measurable Concentration Time Point (AUC0-last) of Vemurafenib on Day 20
Timepoint [3] 0 0
Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose on Day 20
Secondary outcome [4] 0 0
Dose-Normalized AUC from Time 0 to Infinity (AUC0-8) of Vemurafenib on Day 20
Timepoint [4] 0 0
Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose on Day 20
Secondary outcome [5] 0 0
Dose-Normalized Cmax of Vemurafenib on Day 1
Timepoint [5] 0 0
Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose on Day 1
Secondary outcome [6] 0 0
Time to Maximum Concentration (tmax) of Vemurafenib on Day 1 and Day 20
Timepoint [6] 0 0
Day 1: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose; Day 20: Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose
Secondary outcome [7] 0 0
Half-life (t1/2) of Vemurafenib in Plasma on Day 20
Timepoint [7] 0 0
Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose on Day 20
Secondary outcome [8] 0 0
Dose Normalized Apparent Clearance (CL/F) of Vemurafenib on Day 20
Timepoint [8] 0 0
Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose on Day 20
Secondary outcome [9] 0 0
Trough Plasma Concentration (Cmin or Ctrough) of Vemurafenib
Timepoint [9] 0 0
Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose on Day 1; Pre-dose (0 hour); 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours after the morning dose on Day 20; Before the morning dose on Days 9 and 15

Eligibility
Key inclusion criteria
- Histologically confirmed BRAF V600 mutation-positive advanced solid malignancy that is
metastatic or unresectable and for which standard curative or palliative measures do
not exist or are no longer effective

- Normal or impaired hepatic function (hepatic function will be classified according to
the NCI Organ Dysfunction Working Group criteria)

- For participants with hepatic impairment: Stable hepatic function for at least 2 weeks
(greater than [>] 14 days) before Day 1

- Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to
(</=) 2

- Participants with a history of recent brain metastases must have completed any
radiation therapy at least 4 weeks before Day 1, be without intervening signs of brain
lesion progression and not require steroids before starting the protocol (Day 1).
Participants with gliomas or known brain metastases who require anticonvulsants must
be seizure free for 1 month prior to enrollment

- Life expectancy greater than or eual to (>/=) 8 weeks

- Adequate hematologic and renal function

- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive methods that result in a failure rate
of less than (<) 1 percent per year during the treatment period and for at least 6
months after the last dose of study drug
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Allergy or hypersensitivity to components of the vemurafenib formulation

- Requirement for immediate or urgent treatment with twice a day vemurafenib and for
whom the intermittent schedule of vemurafenib employed during Days 1-26 of this trial
is not clinically acceptable

- Chemotherapy, biologic therapy, immunotherapy, or radiotherapy within 4 weeks prior to
entering the study, or those who have not recovered from AEs because of agents
administered more than 4 weeks earlier

- Gliomas or known brain metastases that require corticosteroids

- History of clinically significant cardiac or pulmonary dysfunction

- Human Immunodeficiency Virus (HIV)-positive participant requiring antiviral treatment
including protease inhibitors

- Active infection or chronic infection requiring chronic suppressive antibiotics

- Pregnancy or breastfeeding at Day 1

- History of malabsorption or other clinically significant metabolic dysfunction

- Active autoimmune disease

- Current, recent (within 28 days prior to Day 1), or planned use of any investigational
product outside this study

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/08/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
20/04/2017
Sample size
Target
Accrual to date
Final
8
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peninsula and South Eastern Haematology and Oncology Grou - Frankston
Recruitment postcode(s) [1] 0 0
3199 - Frankston
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
Greece
State/province [2] 0 0
Athens
Country [3] 0 0
Israel
State/province [3] 0 0
Haifa
Country [4] 0 0
Israel
State/province [4] 0 0
Tel Aviv
Country [5] 0 0
Russian Federation
State/province [5] 0 0
Krasnodar
Country [6] 0 0
Turkey
State/province [6] 0 0
Izmir
Country [7] 0 0
United Kingdom
State/province [7] 0 0
Cardiff

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This open-label, Phase I study will evaluate the impact of severe hepatic impairment on the
pharmacokinetics and safety of vemurafenib in participants with BRAF V600 mutation positive
cancer. Participants will receive vemurafenib 960 milligrams (mg) (normal hepatic function)
or 720 mg (severe hepatic impairment) orally twice daily (BID) on Days 1 to 20 (morning dose)
and from Day 27 onward until disease progression or unacceptable toxicity occurs.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01767623
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01767623