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

SWOG Cancer Research Network

Status and phase: Completed; Phase 1

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

Treatments: Drug: BMS-247550

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00049400

U01CA076642 (U.S. NIH Grant/Contract)

S0355 (Other Identifier)

U10CA032102 (U.S. NIH Grant/Contract)

P30CA016087 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 78 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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78 participants in 1 patient group

treatment

Experimental group

Description:

Single-arm, dose-escalation of BMS-247550

Treatment:

Drug: BMS-247550