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

Roche

Status and phase: Completed; Phase 1

Conditions: Neoplasms

Treatments: Drug: Vemurafenib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01767623

GO28053

2012-003820-18 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 8 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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8 participants in 2 patient groups

Cohort 1: Participants with Normal Liver Function

Active Comparator group

Description:

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.

Treatment:

Drug: Vemurafenib

Cohort 2: Participants with Severe Liver Dysfunction

Experimental group

Description:

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:

Drug: Vemurafenib