solid tumors cancerous disease with BrafV600 specific mutation
Conditions
Interventions
Following a screening period of up to 28 days, patients will receive
acenocoumarol 4 mg
orally (PO) on Day 1 (Period A) under fasted conditions of at least 10 hours.
In Period B, patients will receiv
Sponsors
Hoffmann-La Roche
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Patients with either unresectable Stage IIIc or Stage IV metastatic melanoma positive for the BRAFV600 mutation or other malignant tumor type, which harbors a V600-activating mutation of BRAF, as determined by the results of cobas 4800 BRAF V600 Mutation Test or a DNA sequencing method (e.g., Sanger), and who have no acceptable standard treatment options;• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2;• Male or female patients between 18 and 70 years of age (inclusive);• Ability to participate and willingness to give written informed consent prior to any study related procedures and to comply with the study protocol;• Life expectancy >= 12 weeks;• Full recovery from the effects of any major surgery or significant traumatic injury at least 14 days prior to the first dose of study treatment;• Adequate hematologic and end organ function;• Female patients of childbearing potential and male patients with partners of childbearing potential must agree to always use 2 effective methods of contraception including at least 1 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;• Negative serum or urine pregnancy test results within 7 days prior to commencement of dosing in women of childbearing potential; women not of childbearing potential may be included if they are either surgically sterile or have been naturally menopausal for >= 1 year. Women not of childbearing potential need not undergo pregnancy testing.;• Absence of any psychological, familial, sociological, or geographical condition that could potentially hamper compliance with the study protocol and follow-up schedule; such conditions should be discussed with the patient before trial entry.
Exclusion criteria
Exclusion criteria: • Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of Day 1;• Prior anti-cancer therapy (e.g., biologic or other targeted therapy, chemotherapy, or hormonal therapy) within 28 days (6 weeks for nitrosoureas or mitomycin C, or 14 days for hormonal therapy or kinase inhibitors) before the first dose of study treatment in Period A, Day 1;• Palliative radiotherapy within 2 weeks prior to first dose of study drug treatment in Period A, Day 1 • Experimental therapy within 4 weeks prior to first dose of study drug treatment in Period A, Day 1;• History of clinically significant cardiac or pulmonary dysfunction, including: current uncontrolled Grade >= 2 hypertension or unstable angina;• Current Grade >= 2 dyspnea or hypoxia or need for supplemental oxygen;• History of symptomatic congestive heart failure of any New York Heart Association class or serious cardiac arrhythmia requiring treatment, with the exceptions of atrial fibrillation and paroxysmal supraventricular tachycardia;• History of myocardial infarction within 6 months prior to first dose of study treatment;• Current dyspnea at rest due to complications of advanced malignancy, or any requirement for supplemental oxygen to perform activities of daily living;• History of congenital long QT syndrome or corrected QT (QTc) > 450 msec;• Active central nervous system lesions (i.e., patients with radiographically unstable, symptomatic lesions);• Patients with VKORC1 mutatie (1639G*A, 1173C*T) in either one allele (heterozygoos) or two alleles (homozygous) • Patients with CYP2C9*3 allele mutation in either one allele (heterozygoos) or two alleles (homozygous) • Patients with a history of bleeding or coagulation disorders;• Allergy or hypersensitivity to vemurafenib or acenocoumarol formulation ;• Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease);• Inability or unwillingness to swallow pills;• History of malabsorption or other condition that would interfere with enteral absorption of study treatment;• History of clinically significant liver disease (including cirrhosis), current alcohol abuse, or known infection with human immunodeficiency virus (HIV) requiring antiretroviral treatment, acquired immune deficiency syndrome (AIDS)*related illness, or active heaptitis B or hepatitis C virus;• Uncontrolled ascites requiring weekly large-volume paracentesis for 3 consecutive weeks prior to enrollment;• Pregnancy, lactation, or breastfeeding;• Unwillingness or inability to comply with study and follow-up procedures;• Need to take a concomitant medication, dietary supplement, or food that is prohibited during the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The following PK parameters for R* and S*acenocoumarol will be obtained using non*compartmental analysis methods: • Area under the plasma concentration-time curve (AUC) from Time 0 to last measurable concentration timepoint (AUC0*T) • AUC from Time 0 to infinity (AUC0**) • Maximum plasma concentration (Cmax) • Time to maximum plasma concentration (Tmax) • Terminal half-life (t1/2) • Apparent clearance (CL/F) | — |
Secondary
| Measure | Time frame |
|---|---|
| The safety outcome measures for this study are as follows: • Incidence, nature, and intensity (severity) of AEs and SAEs, graded according to the NCI CTCAE (Version 4.0) | — |
Countries
Netherlands
Outcome results
None listed