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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase I Pharmacokinetic Study Of Epothilone B Analogue BMS-247550 (NSC 710428D) In Patients With Advanced Malignancies And Varying Levels Of Liver Dysfunction

Conditions
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Lymphoma, Small Intestine Cancer, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: BMS-247550


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment<br>Single-arm, dose-escalation of BMS-247550 | Drug: BMS-247550<br>* BMS-247550 as a 3-hour infusion on Day 1 of a three-week cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| dose defining |  | Treatment delays >2 weeks constitute a DLT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression | 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. | 30 days after going off study | 
| Symptomatic deterioration | Global deterioration of health status requiring discontinuation of treatment without objective evidence of progression. | 30 days after going off study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, intraocular lymphoma, primary central nervous system lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult Hodgkin lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult T-cell leukemia/lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent grade 1, 2, or 3 follicular lymphoma, recurrent mantle cell lymphoma, small intestine lymphoma, stage IV adult diffuse large cell or mixed cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult Burkitt lymphoma or Hodgkin lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV adult T-cell leukemia/lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma, stage IV grade 1, 2, or 3 follicular lymphoma, stage IV mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, stage IV marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of MALT, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, recurrent adult Burkitt lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma