A Study of The Impact of Severe Hepatic Impairment on the Pharmacokinetics and Safety of Vemurafenib in BRAF V600 Mutation-Positive Cancer Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01767623
First received: January 11, 2013
Last updated: August 4, 2014
Last verified: August 2014
  Purpose

This open-label, Phase I study will evaluate the impact of severe hepatic impair ment on the pharmacokinetics and safety of vemurafenib in patients with BRAF V60 0 mutation positive cancer. Patients will receive vemurafenib 960 mg (normal hep atic function) or 720 mg (severe hepatic impairment) orally twice daily on Days

1 to 20 (morning dose) and from Day 27 onwards until disease progression or inac ceptable toxicity occurs.


Condition Intervention Phase
Neoplasms
Drug: vemurafenib
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Dose-normalized area under the concentration-time curve (AUC) during the dose interval on Day 20 (steady state) [ Time Frame: Pre-dose and up to 168 hours after the morning dose Day 20 ] [ Designated as safety issue: No ]
  • Dose-normalized maximum concentration (Cmax) on Day 20 (steady state) [ Time Frame: Pre-dose and up to 168 hours after the morning dose on Day 20 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety: Incidence of adverse events [ Time Frame: approximately 1.5 years ] [ Designated as safety issue: No ]
  • Dose-normalized AUC on Day 1 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Dose-normalized AUC on Day 20 [ Time Frame: Day 20 ] [ Designated as safety issue: No ]
  • Dose-normalized Cmax on Day 1 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Time to maximum concentration (tmax) on Day 1 and 20 [ Time Frame: Days 1 and 20 ] [ Designated as safety issue: No ]
  • Half-life (t1/2) in plasma on Day 20 [ Time Frame: Day 20 ] [ Designated as safety issue: No ]
  • Dose-normalized clearance (CL/F) on Day 20 [ Time Frame: Day 20 ] [ Designated as safety issue: No ]
  • Trough plasma concentration (Cmin or Ctrough) [ Time Frame: up to Day 20 ] [ Designated as safety issue: No ]

Estimated Enrollment: 16
Study Start Date: August 2013
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Cohort 1: normal liver function Drug: vemurafenib
960 mg BID
Experimental: Cohort 2: severe liver dysfunction Drug: vemurafenib
720 mg BID

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients, >/= 18 years of age
  • 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 patients with hepatic impairment: Stable hepatic function for at least 2 weeks before Day 1
  • Eastern Cooperative Oncology Group (ECOG) performance status of </=2
  • Patients 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). Patients with gliomas or known brain metastases who require anticonvulsants must be seizure free for 1 month prior to enrollment
  • Life expectancy > 8 weeks
  • Adequate hematologic and renal function
  • Females patients of childbearing potential and male patients with female partners of childbearing potential must agree to use two adequate methods of contraception as defined by protocol during the course of this study and for at least 6 months after completion of study treatment

Exclusion Criteria:

  • Allergy or hypersensitivity to components of the vemurafenib formulation
  • Requirement for immediate or urgent treatment with vemurafenib and for whom the intermittent schedule of vemurafenib employed during Days 1-26 in 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
  • HIV-positive patient 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01767623

Contacts
Contact: Reference Study ID Number: GO28053 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com

Locations
United States, California
Recruiting
Encinitas, California, United States, 92008
Australia, Victoria
Recruiting
Frankston, Victoria, Australia, 3199
Greece
Recruiting
Athens, Greece, 11527
Israel
Recruiting
Haifa, Israel, 31096
Recruiting
Tel Aviv, Israel, 6423906
Russian Federation
Recruiting
Krasnodar, Russian Federation, 350040
Turkey
Recruiting
Izmir, Turkey, 35100
United Kingdom
Recruiting
Cardiff, United Kingdom, CF14 2TL
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01767623     History of Changes
Other Study ID Numbers: GO28053, 2012-003820-18
Study First Received: January 11, 2013
Last Updated: August 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on August 27, 2014