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

NCT01767623

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

A Study of The Impact of Severe Hepatic Impairment on the Pharmacokinetics and Safety of Vemurafenib in <span class="go-doc-concept go-doc-biomarker">BRAF</span> V600 <span class="go-doc-concept go-doc-keyword">Mutation</span>-Positive Cancer Patients

Title

  • Brief Title: A Study of The Impact of Severe Hepatic Impairment on the Pharmacokinetics and Safety of Vemurafenib in BRAF V600 Mutation-Positive Cancer Patients
  • 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
  • Clinical Trial IDs

    NCT ID: NCT01767623

    ORG ID: GO28053

    NCI ID: 2012-003820-18

    Trial Conditions

    Neoplasms

    Trial Interventions

    Drug Synonyms Arms
    vemurafenib Cohort 1: normal liver function
    vemurafenib Cohort 2: severe liver dysfunction

    Trial Purpose

    This open-label, Phase I study will evaluate the impact of severe hepatic impairment on the
    pharmacokinetics and safety of vemurafenib in patients with BRAF V600 mutation positive
    cancer. Patients will receive vemurafenib 960 mg (normal hepatic 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 inacceptable toxicity occurs.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Cohort 1: normal liver function Active Comparator vemurafenib
    Cohort 2: severe liver dysfunction Experimental vemurafenib

    Eligibility 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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Dose-normalized area under the concentration-time curve (AUC) during the dose interval on Day 20 (steady state)

    Dose-normalized maximum concentration (Cmax) on Day 20 (steady state)

    Secondary Outcome Measures

    Safety: Incidence of adverse events

    Dose-normalized AUC on Day 1

    Dose-normalized AUC on Day 20

    Dose-normalized Cmax on Day 1

    Time to maximum concentration (tmax) on Day 1 and 20

    Half-life (t1/2) in plasma on Day 20

    Dose-normalized clearance (CL/F) on Day 20

    Trough plasma concentration (Cmin or Ctrough)

    Trial Keywords