Ixabepilone and Sunitinib Malate in Treating Patients With Progressive Advanced Solid Tumors

Exclusion Criteria

• •Patients with symptomatic/untreated CNS metastases. Patients with known CNS metastases can be enrolled if:
• •CNS metastases have been appropriately treated. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or resection as deemed appropriate by the treating physician. Patients who had surgical resection of CNS metastases or brain biopsy within 3 months prior to Day 1 will be excluded.
• •No ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period.
• •No evidence of progression or hemorrhage after treatment (brain imaging study within 4 weeks of treatment start).
• •CTC Grade 2 or greater neuropathy (motor or sensory) at study entry.
• •Inability to swallow capsules.
• •History of gastrointestinal disease, malabsorption, or requiring use of a feeding tube.
• •Patients who have received any investigational compound within the past 28 days (within 2 weeks for prior RTKI treated patients).
• •Patients who have received radiotherapy for any cause less than 4 weeks prior to study entry.
• •Patients taking cytochrome P450 (CYP) 3A4 enzyme-inducing or enzyme-inhibitor medications like: antiepileptic drugs (phenytoin, carbamazepine or phenobarbital), St John's Wort, ketoconazole, dexamethasone, dysrhythmic drugs (terfenadine, quinidine, procainamide, sotalol, probucolol, bepridil, indapamide, or flecainide), haloperidol, risperidone, rifampin, grapefruit (or juice) within two weeks of registration and during the course of therapy. Topical and inhaled steroids are permitted. Please refer to Appendix VI for a complete list of CYP34A inducers and inhibitors.
• •Patients with known HIV infection are excluded due to the possibility of unknown side effects on the immune system by these agents. The potential impact of pharmacokinetic interactions of anti-retroviral therapy with ixabepilone or sunitinib is unknown. Appropriate studies may be undertaken in patients with HIV and those receiving combination anti-retroviral therapy in the future.
• •Invasive procedures defined as follows:
• •* Major surgical procedure, open biopsy or significant traumatic injury \<= 28 days prior to registration.
• •* Anticipation of need for major surgical procedures during the course of the study.
• •* Core biopsy \<= 7 days prior to registration.
• •* Port placement \<= 7 days prior to registration.
• •* Serious or non-healing wound, ulcer or bone fracture.
• •* History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess \<= 28 days.
• •Evidence of bleeding diathesis or coagulopathy.
• •Ongoing hemoptysis, or cerebrovascular accident \<= previous 6 months, or peripheral vascular disease with claudication on \< 1 block, or history of clinically significant bleeding.
• •Significant cardiovascular disease defined as congestive heart failure (New York Heart Association Class II, III or IV), angina pectoris requiring nitrate therapy, or recent myocardial infarction (\<= the last 6 months). Patients must have an absolute baseline left ventricular ejection fraction (LVEF) \>= 50% by MUGA scan within 4 weeks prior to registration
• •Uncontrolled hypertension (defined as a blood pressure of \> 150 mmHg systolic and/or \> 90 mmHg diastolic on medication).
• •A currently active second malignancy other than non-melanoma skin cancer. Patients are not considered to have a currently active malignancy if they have completed anti-cancer therapy and are considered by their physician to be at less than 30% risk of relapse.
• •Any of the following, as this regimen may be harmful to a developing fetus or nursing child:
• •* Pregnant women
• •* Breastfeeding women
• •* Men or women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (diaphragm, birth control pills, injections, intrauterine device \[IUD\], surgical sterilization, subcutaneous implants, or abstinence, etc.) NOTE: The effects of the agent(s) on the developing human fetus at the recommended therapeutic dose are unknown.
• •Other uncontrolled serious medical or psychiatric condition (e.g. cardiac arrhythmias, diabetes, etc.)
• •Patients must have a QTc interval \< 500 msec on baseline EKG.
• •Prior treatment with ixabepilone.
• •History of chronic or recurrent infection that requires continuous use of anti-viral, anti-fungal or anti-bacterial therapy; or foreseeable need to receive anti-infective therapy within 14 days of Cycle 1 Day 1 treatment.
• •History of Grade 3/4 hypersensitivity reaction to Cremophor EL or its derivatives (polyoxyethylated castor oil).
• •Non-small cell lung cancer (NSCLC) of squamous cell type, or NSCLC of any histology that involves a major blood vessel (e.g. aorta, pulmonary artery, etc)