Рилузол и тозилат сорафениба в лечении пациентов с запущенными солидными опухолями или меланомой

Inclusion Criteria:

• Patients must have histologically proven solid tumors (Phase I) with biopsiable tumor (expansion cohort) refractory to standard therapy or for whom no standard therapy exists or who decline standard therapy
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Patients must be willing and able to sign informed consent
• Unlimited prior therapies are permitted for patients enrolled in the dose escalation phase of the study; patients in the expansion cohort of the study may not have any prior therapy with riluzole or sorafenib and must have biopsiable tumor
• Patients may have measurable or evaluable disease
• Absolute neutrophil count (ANC) >= 1,500/uL
• Platelets >= 100,000/uL
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN
• International normalized ratio (INR) =< 1.5 x institutional ULN
• Creatinine =< 2 x ULN
• Patients with brain lesions that have been treated with whole brain radiotherapy and are clinically stable for at least 4 weeks, are not taking steroids and are not receiving enzyme-inducing anticonvulsants will be eligible

Exclusion Criteria:

• Serious concomitant systemic disorders (including active infections) that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator
• For patients who have received gamma knife or stereotactic radiosurgery, a 2 week washout is required; patients who have had other types of radiotherapy, chemotherapy or biologic agents within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier to =< grade 1; at least 4 weeks must have elapsed since any major surgery; patients with prostate cancer may continue to receive hormonal therapy
• History of allergic reactions attributed to riluzole or sorafenib
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal, barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 2 weeks after discontinuation of riluzole and/or sorafenib; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; pregnant (positive pregnancy test) or lactating patients cannot participate
• Known human immunodeficiency virus (HIV) infection or known history of active hepatitis B or C infection
• Current, recent (within 4 weeks of the first treatment of this study), or planned participation in an experimental drug study (prevention trials are permitted if the trial is not testing a novel experimental agent)
• Cardiac disease: congestive heart failure > class II New York Heart Association (NYHA); patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
• History of stroke within six months
• Clinically significant peripheral vascular disease
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
• Uncontrolled hypertension, defined as systolic blood pressure > 150 mm Hg or diastolic blood pressure > 90 mm Hg, despite optimal medical management
• Active clinically serious infection > Common Terminology Criteria for Adverse Events (CTCAE) grade 2
• Any of the following within 6 months prior to first dose of treatment: myocardial infarction, symptomatic coronary artery disease (severe or unstable angina), artery bypass graft, uncontrolled arrhythmias, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolus
• Pulmonary hemorrhage/bleeding event >= CTCAE grade 2 within 4 weeks of first-dose of study drug
• Any other hemorrhage/bleeding event >= CTCAE grade 3 within 4 weeks of first dose of study drug
• Evidence or history of bleeding diathesis or coagulopathy
• Major surgery or significant traumatic injury within 4 weeks of first study drug
• The eligibility of patients taking medications that are potent modulators of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4), cytochrome P450, family 2, subfamily B, polypeptide 6 (CYP2B6), subfamily 2, polypeptide 8 (2C8) will be determined following a review of their case by the principal investigator; every effort should be made to switch patients taking such agents or substances to other medications
• Any condition that impairs the patient's ability to swallow whole pills
• Any malabsorption problem
• Anticipation of need for major surgical procedure during the course of the study
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 1 of treatment
• Serious, non-healing wound, ulcer, or bone fracture
• Inability to comply with study and/or follow-up procedures
• Anticoagulation with Lovenox (enoxaparin) is permitted, however, patients on anticoagulation with warfarin are not permitted on this study