Ixabepilone and Temsirolimus in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery

PRIMARY OBJECTIVES:

I. To determine the maximally tolerated dose (MTD) of the combination of ixabepilone and
temsirolimus in patients with advanced solid tumors.

II. To describe toxicity profiles associated with the combination of ixabepilone and
temsirolimus.

III. To assess preliminary efficacy of the combination of ixabepilone and temsirolimus.

OUTLINE: This is a dose-escalation study.

Patients receive ixabepilone intravenously (IV) over 3 hours on day 1 and temsirolimus IV
over 30-60 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 3 months.

Inclusion Criteria:

- Adult patients with histologically confirmed solid tumor malignancy that is metastatic
or unresectable and for which standard curative measures or other therapy that provide
survival benefit do not exist or are no longer effective

- Patients may not have had more than two systemic therapeutic regimens in the
metastatic disease setting with the following exceptions: hormonal therapy (e.g.
tamoxifen, aromatase inhibitors, anti-androgen therapy, etc.)

- Patients with non-measurable, but assessable, disease will be allowed

- Absolute neutrophil count >= 1500/mcL

- Hemoglobin >= 9.0 g/dL

- Platelets >= 100,000/mcL

- Total bilirubin < 1.5 mg/dL

- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) or serum
glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2.5 x
institutional upper limit of normal (ULN) in the absence of hepatic metastasis; SGPT
(ALT) =< 3 x ULN or SGOT (AST) =< 5 x ULN in the presence of hepatic metastasis

- Creatinine =< 1.5 x ULN

- International normalized ratio (INR) =< 1.4 for patients not on warfarin (Coumadin)

- INR range of 2.0-3.0 for patients on therapeutic doses of warfarin (Coumadin)

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

- Ability to provide informed consent

- Willingness to return to a Mayo Clinic institution for follow up

- Life expectancy >= 84 days (12 weeks)

- Women of childbearing potential only: negative serum pregnancy test done =< 7 days
prior to registration

Exclusion Criteria:

- Known standard therapy for the patient's disease that is potentially curative or
definitely capable of extending life expectancy

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, uncontrolled diabetes or with hemoglobin A1c (HbA1C) > 8, or psychiatric
illness/social situations that would limit compliance with study requirements

- Any of the following prior therapies:

- Chemotherapy =< 28 days prior to registration

- Mitomycin C/nitrosoureas =< 42 days prior to registration

- Immunotherapy =< 28 days prior to registration

- Biologic therapy =< 28 days prior to registration

- Radiation therapy =< 28 days prior to registration

- Radiation to > 25% of bone marrow

- Failure to fully recover from acute, reversible effects of prior chemotherapy
regardless of interval since last treatment

- New York Heart Association classification III or IV

- Known central nervous system (CNS) metastases or seizure disorder; patients with known
brain metastases that have been successfully treated and stable for > 6 months without
requirement for corticosteroids and without seizure activity will be eligible

- Any of the following:

- Pregnant women

- Nursing women

- Men or women of childbearing potential who are unwilling to employ adequate
contraception

- Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy
considered investigational (utilized for a non-Food and Drug Administration
[FDA]-approved indication and in the context of a research investigation)

- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
of the investigator, would make the patient inappropriate for entry into this study or
interfere significantly with the proper assessment of safety and toxicity of the
prescribed regimens

- Immunocompromised patients (other than that related to the use of corticosteroids)
including patients known to be human immunodeficiency virus (HIV) positive

- Receiving any other investigational agent which would be considered as a treatment for
the primary neoplasm

- History of myocardial infarction =< 168 days (6 months), or congestive heart failure
requiring use of ongoing maintenance therapy for life-threatening ventricular
arrhythmias

- >= Grade 2 sensory neuropathy

- >= Grade 2 hypertriglyceridemia

- >= Grade 2 hypercholesterolemia

- Patients on medication considered strong cytochrome P450 3A4 (CYP3A4) inducers
(efavirenz, nevirapine, carbamazepine, phenobarbital, phenytoin, pioglitazone,
rifabutin, rifampin, St. John's wort) or CYP3A4 inhibitors (indinavir, nelfinavir,
ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone, saquinavir,
telithromycin) unless the medication can be substituted with another agent