Phase I Study of Tipifarnib (IND#58359, R115777) and Sorafenib (IND#69896, BAY 43-9006) in Patients With Biopsiable Advanced Cancers

Inclusion Criteria:

• Patients must have had =< 4 prior chemotherapy regimens

  • Patients must have advanced cancer that is refractory to standard therapy or for whom there is no standard therapy that increases survival by three months
• ECOG performance status =< 2 (Karnofsky >= 60%)
• Life expectancy of greater than 12 weeks
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin =< 1.5
• AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal
• Creatinine within normal institutional limits OR - creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal (a calculated CrCL is acceptable)
• INR/PT =< within institutional guidelines for biopsy procedures ( =< 16 seconds)
• Eligibility of patients receiving any other medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of BAY 43-9006 or R115777 will be determined following review of their case by the Principal Investigator
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document
• Tumor accessible for repeat biopsies

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 4 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 4 weeks earlier
• Patients may not be receiving any investigational agents other than BAY 43-9006 and R115777
• Patients with known brain metastases are excluded except for patients who have had treated brain metastases and are currently not taking anti-seizure medications or steroids
• Patients may not have allergies to imidazoles (e.g., clotrimazole, ketoconazole, miconazole, econazole) or a history of allergic reactions attributed to any other compound of similar chemical or biologic composition to either BAY 43-9006 or R115777
• Uncontrolled hypertension with systolic blood pressure of >140 mmHg or diastolic pressure >90 mmHg; however, patients with well-controlled hypertension are eligible
• Patients must not have any evidence of current history of bleeding diathesis
• Patients may not have grade 2 or greater peripheral neuropathy
• Patients with any condition that impairs their ability to swallow pills are excluded
• Patients cannot be receiving EIAEDs (e.g., phenytoin, carbamazepine, phenobarbital) nor any other CYP3A4 inducer such as rifampin or St. John's wort
• Uncontrolled intercurrent illness including, but not limited to, uncontrolled hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients with a NYHA classification >2
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated
• HIV-positive patients on combination antiretroviral therapy are ineligible