| Exclusion Criteria: | 1) 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 to grade 1 toxicity (except for peripheral neuropathy, for which </= grade 2 toxicity is allowed to participate) from adverse events due to agents administered more than 4 weeks earlier.
2) For phase II study portion, patients may not have previously received either BAY43-9006 or CCI-779 or any other agents targeting raf, VEGF/VEGFR, or mTOR. However, for phase I study portion, this exclusion criterion does not apply.
3) Patients may not be receiving any investigational agents other than BAY43-9006 and CCI-779.
4) Patients with known brain metastases are excluded because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound evaluation of neurologic and other adverse events. The following exception is allowed: patients without radiographical evidence of recurrence in the brain for >/= 3 months after complete resection of brain metastases or who have asymptomatic brain metastases stable for >/= 3 months since whole brain radiation therapy and/or stereotactic radiosurgery are eligible. Patients must not require steroid treatment for brain metastases.
5) History of allergic reactions attributed to compounds of similar chemical or biologic composition to BAY43-9006 or CCI-779.
6) Uncontrolled hypertension with systolic blood pressure of > 140 mmHg on 2 separate days within 1 week before enrollment or diastolic pressure > 90 mmHg on 2 separate days within 1 week before enrollment. However, patients with well-controlled hypertension are eligible.
7) Patients must not have any evidence of bleeding diathesis or coagulopathy.
8) Patients on full-dose anticoagulation (i.e. warfarin, IV heparin, low-molecular weight heparin).
9) Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow pills are excluded.
10) 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.
11) Pregnant women are excluded from this study because BAY43-9006 is a serine-threonine kinase inhibitor and CCI-779 is an mRNA translation inhibitor, both of which have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with BAY43-9006 or CCI-779, breastfeeding should be discontinued if the mother is treated with either of these agents.
12) HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with BAY43-9006 and/or CCI-779. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
13) Patients undergoing major surgery or a sustaining a significant traumatic injury within 21 days prior to treatment are ineligible. |