BMS-247550 in Treating Patients With Liver or Gallbladder Cancer

Study Overview
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Brief Summary
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Phase II trial to study the effectiveness of BMS-247550 in treating patients who have liver or gallbladder cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the objective response rate of patients with hepatobiliary cancer treated with BMS-247550. II. Determine the toxicity of this drug in these patients. III. Determine the duration of response, median and overall survival, and time to progression in patients treated with this drug. OUTLINE: This is a multicenter study. Patients receive BMS-247550 IV over 3 hours on day 1. Treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 6 weeks until disease progression

Official Title
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A Phase II Trial Of The Epothilone B Analog BMS-247550 (NSC 710428D) In Patients With Hepatobiliary Cancer

Conditions
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Advanced Adult Primary Liver Cancer, Adult Primary Cholangiocellular Carcinoma, Adult Primary Hepatocellular Carcinoma, Cholangiocarcinoma of the Extrahepatic Bile Duct, Cholangiocarcinoma of the Gallbladder, Localized Extrahepatic Bile Duct Cancer, Localized Gallbladder Cancer, Localized Resectable Adult Primary Liver Cancer, Localized Unresectable Adult Primary Liver Cancer, Recurrent Adult Primary Liver Cancer, Recurrent Extrahepatic Bile Duct Cancer, Recurrent Gallbladder Cancer, Unresectable Extrahepatic Bile Duct Cancer, Unresectable Gallbladder Cancer

Intervention / Treatment
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* Drug: ixabepilone
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed locally advanced, metastatic, or recurrent hepatobiliary cancer Liver (hepatocellular) Bile duct (cholangiocarcinoma) Gallbladder At least 1 unidimensionally measurable lesion At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan The following are not considered measurable lesions: Lesions seen on colonoscopic examination or barium studies Bone metastases CNS lesions Ascites No brain metastases Performance status - ECOG 0-2 At least 3 months WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Bilirubin no greater than 1.5 mg/dL AST/ALT no greater than 2.5 times upper limit of normal Creatinine no greater than 1.5 mg/dL Creatinine clearance at least 60 mL/min No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No grade 2 or greater peripheral neuropathy No other uncontrolled concurrent illness No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance No prior allergic hypersensitivity reaction attributed to compounds containing Cremophor EL (e.g., paclitaxel or compounds of similar chemical or biological composition to BMS-247550) No other currently active malignancy except nonmelanoma skin cancer, carcinoma in situ of the cervix, or cancer for which patient has completed therapy and is at less than 30% risk of relapse Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No concurrent immunotherapy No prior chemotherapy No other concurrent chemotherapy No concurrent hormonal therapy No concurrent therapeutic radiotherapy At least 30 days since prior investigational agents At least 7 days since prior cimetidine No concurrent cimetidine No other concurrent commercial or investigational anticancer agents or therapies No concurrent unconventional therapies, food, or vitamin supplements (e.g., St. John's Wort) No concurrent combination antiretroviral therapy for HIV-positive patients

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 (ixabepilone)<br>Patients receive BMS-247550 IV over 3 hours on day 1. Treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity. | Drug: ixabepilone<br>* Given IV<br>* Other names: Ixempra;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (partial or complete response) evaluated by RECIST | A 10% response rate precludes further study whereas a 25% response rate would indicate that further study is warranted. | Up to 8 years | 
| Frequency and extent of cytotoxic activity graded according to the NCI CTC Version 2.0 |  | Up to 8 years | 
| Time to disease progression | Will also be evaluated using the Kaplan-Meier estimator. | From the first day of treatment until the date PD or death is first reported, assessed up to 8 years | 
| Overall survival | Will also be evaluated using the Kaplan-Meier estimator. | From the time measurement criteria are met for CR/PR (whichever is first recorded) until the first date that PD is objectively documented, assessed up to 10 years |