S0355 Ixabepilone in Treating Patients With Advanced Solid Tumors or Lymphomas and Liver Dysfunction

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase I trial is studying the side effects and best dose of ixabepilone in treating patients with advanced solid tumors or lymphomas and liver dysfunction.

OBJECTIVES:

* Determine the levels of hepatic impairment at which dose modifications of ixabepilone are required in patients with advanced solid tumors or lymphomas and varying levels of liver dysfunction.
* Determine the effect of hepatic dysfunction on the plasma pharmacokinetics of this drug in these patients.
* Determine the toxic effects of this drug at varying levels of hepatic dysfunction in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to liver function (normal vs mild dysfunction vs moderate dysfunction vs severe dysfunction).

Patients receive ixabepilone IV over 3 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of ixabepilone until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, at least 6 but no more than 12 patients are treated at the recommended phase II dose.

Patients are followed for 30 days.

PROJECTED ACCRUAL: A total of 12-84 patients (6-12 for stratum 1; 2-18 for stratum 2; 2-24 for stratum 3; and 2-30 for stratum 4) will be accrued for this study within 12 months.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed solid tumor or lymphoma for which standard curative or palliative measures do not exist or are no longer effective

  * Pathological confirmation of diagnosis not required in patients with liver mass, raised alpha-fetoprotein levels (at least 500 ng/mL), and positive serology for hepatitis consistent with a diagnosis of hepatocellular carcinoma
  * Any solid tumor or lymphoma tumor type eligible
  * Must have had thoracic and upper abdominal CT scan, including entire liver and adrenals, within 28 days before study entry
* Patients with glioma or brain metastases must be on a stable dose of corticosteroids and be seizure-free for the past month

  * Prior whole brain or gamma knife radiotherapy required for known brain metastases
  * No unstable or untreated (non-irradiated) brain metastases

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* Zubrod 0-2

Life expectancy

* Not specified

Hematopoietic

* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3
* No active hemolysis

Hepatic

* See Disease Characteristics
* Patients with biliary obstruction for which a shunt has been placed are allowed if shunt is in place for at least 10 days and liver function is stable
* Abnormal liver function (bilirubin and SGOT) allowed regardless of cause (metastases or other causes)
* No evidence of biliary sepsis

Renal

* Creatinine no greater than 1.5 mg/dL

Cardiovascular

* No symptomatic congestive heart failure
* No unstable angina pectoris
* No cardiac arrhythmia

Other

* No concurrent uncontrolled illness
* No ongoing or active infection
* No uncontrolled diarrhea
* No peripheral neuropathy grade II or greater
* No psychiatric illness or social situation that would preclude study compliance
* HIV negative
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective barrier contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No concurrent immunotherapy for malignancy

Chemotherapy

* More than 2 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
* No other concurrent chemotherapy for malignancy

Endocrine therapy

* See Disease Characteristics
* No concurrent oral contraceptives
* No concurrent hormone therapy for malignancy

  * Concurrent luteinizing hormone-releasing hormone agonists allowed

Radiotherapy

* See Disease Characteristics
* More than 4 weeks since prior radiotherapy and recovered
* No concurrent radiotherapy for malignancy

Surgery

* More than 2 weeks since prior major surgery

Other

* Recovered from prior therapy
* No concurrent medications that are known to be inhibitors of CYP3A4