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