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

• Status: Completed
• Trial end date: 2017-04-20
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hoffmann-La Roche
• Treatments: Vemurafenib

Criteria

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 (
• 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