None listed
Conditions
Interventions
Vemurafenib 240mg coated tablets, oral route of administration.
Test Product
Period A: Patients in first cohort (normal hepatic function) will receive oral vemurafenib 960 mg BID
on Days 1 to
Sponsors
F. HOFFMANN-LA ROCHE LTD.,
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: Disease-Specific Inclusion Criteria: Histologically confirmed BRAFV600 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. The BRAFV600 mutation−positive status of the underlying malignancy must be established using the cobas® BRAF V600 Mutation Test or a DNA sequencing method (e.g., Sanger) performed in CLIA-certified laboratory or equivalent. • Normal or impaired hepatic function. Hepatic function will be classified according to the NCI Organ Dysfunction Working Group criteria: • normal hepatic function: total bilirubin ≤ upper limit of normal (ULN) and AST ≤ULN • severe hepatic impairment: total bilirubin 3−10 × ULN and AST any value • For patients with hepatic impairment: Stable hepatic function for at least 2 weeks (> 14 days) before Day 1. Stable hepatic function is defined as: patients must continue to meet the criteria for severe hepatic impairment defined above (i.e., total bilirubin 3−10 ×ULN). In addition, there should be no evidence of acute clinical exacerbation of hepatic disease. • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤2 • Patients with a history of recent brain metastases must have completed any radiation therapy (whole brain or gamma knife) 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. General Inclusion Criteria: • Male or female patient age ≥ 18 years • Life expectancy ≥ 8 weeks • Able to participate and willing to give written informed consent prior to performance of any study-related procedures and to comply with the study protocol • Adequate hematologic and renal function, as defined by the following laboratory results obtained within 14 days prior to Day 1: • Absolute neutrophil count ≥ 1.5 × 109/L • Platelet count ≥ 50 × 109/L • Hemoglobin ≥ 9 g/dL • Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation (Cockcroft and Gault 1976): [(140 − age) × (weight in kg) × (0.85 if female)] ÷ [72 × (serum creatinine in mg/dL)] • Female patients of childbearing potential and male patients with partners of childbearing potential must agree to always use two adequate methods of contraception including at least one method with a failure rate of < 1% per year during the course of this study and for at least 6 months after completion of study treatment. • Female patients of childbearing potential are defined as sexually mature women without prior hysterectomy who have had any evidence of menses in the past 12 months. • In order to be considered not of childbearing potential, amenorrhea for a period of 12 months or longer must have occurred in the absence of chemotherapy, anti-estrogen therapy, or ovarian suppression. • Effective forms of contraception include surgical sterilization, a reliable barrier method with spermicide, birth control pills/patches, intra-uterine contraceptive device, or
Exclusion criteria
Exclusion criteria: Cancer-Related Exclusion Criteria: • Allergy or hypersensitivity to components of the vemurafenib formulation • Requirement for immediate or urgent treatment with twice daily 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 Cardiac Exclusion Criteria: • History of clinically significant cardiac or pulmonary dysfunction, including the following: • Current uncontrolled, Grade ≥ 2 hypertension (treated or untreated) or unstable angina • Current Grade ≥ 2 dyspnea or hypoxia or need for supplemental oxygen • History of symptomatic congestive heart failure of Grade II through IV (New York Heart Association Class) • Serious cardiac arrhythmia requiring treatment, with the exceptions of atrial fibrillation and paroxysmal supraventricular tachycardia • History of myocardial infarction within 6 months prior to Day 1 • History of congenital long QT syndrome or QTc interval > 450 ms at baseline • History of an uncorrectable electrolyte disorder affecting serum levels of potassium, calcium, or magnesium General Exclusion Criteria: • Major surgical procedure or significant traumatic injury within 4 weeks prior to the first dose of vemurafenib treatment • HIV-positive patient requiring antiviral treatment including protease inhibitors (e.g., indinavir, nelfinavir, ritonavir or saquinavir) within 4 weeks before or during study treatment • Active infection or chronic infection requiring chronic suppressive antibiotics • Pregnancy or breastfeeding at Day 1 • Active autoimmune disease (e.g., systemic lupus erythematosus, autoimmune vasculitis, inflammatory bowel disease) • History of malabsorption or other clinically significant metabolic dysfunction • Any other serious concomitant medical condition that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient’s ability to participate in the study • Requirement for a concomitant medication or dietary supplement that is prohibited during the study • Unwillingness or inability to comply with study and follow-up procedures • Current, recent (within 28 days prior to Day 1), or planned use of any investigational product outside of this study
Countries
Greece, Israel, Peru, Russian Federation, Turkey, United Kindgdom
Contacts
Public ContactGabriela Celina Loyola
IQVIA RDS Peru S.R.L
Outcome results
None listed