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

NCT ID: NCT00049400

Last Updated: 2015-04-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-10-31
• Study Completion Date: 2007-12-31

Brief Summary

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

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

treatment

Single-arm, dose-escalation of BMS-247550

Group Type: EXPERIMENTAL

BMS-247550

Intervention Type: DRUG

BMS-247550 as a 3-hour infusion on Day 1 of a three-week cycle

Interventions

BMS-247550

BMS-247550 as a 3-hour infusion on Day 1 of a three-week cycle

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Angela Davies, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Davis

Chris H. Takimoto, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute for Drug Development

Locations

City of Hope Comprehensive Cancer Center

Duarte, California, United States

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States

University of California Davis Cancer Center

Sacramento, California, United States

Cardinal Bernardin Cancer Center at Loyola University Medical Center

Maywood, Illinois, United States

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center

Kansas City, Kansas, United States

Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Community Oncology Group at Cleveland Clinic Cancer Center

Independence, Ohio, United States

Cleveland Clinic - Wooster

Wooster, Ohio, United States

Brooke Army Medical Center

Fort Sam Houston, Texas, United States

Wilford Hall Medical Center

Lackland Air Force Base, Texas, United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

St. Joseph Hospital Community Cancer Center

Bellingham, Washington, United States

Olympic Hematology and Oncology

Bremerton, Washington, United States

Skagit Valley Hospital Cancer Care Center

Mount Vernon, Washington, United States

Group Health Central Hospital

Seattle, Washington, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Harborview Medical Center

Seattle, Washington, United States

Swedish Cancer Institute at Swedish Medical Center - First Hill Campus

Seattle, Washington, United States

University Cancer Center at University of Washington Medical Center

Seattle, Washington, United States

North Puget Oncology at United General Hospital

Sedro-Woolley, Washington, United States

Cancer Care Northwest - Spokane South

Spokane, Washington, United States

Wenatchee Valley Medical Center

Wenatchee, Washington, United States

Countries

United States

References

Takimoto CH, Liu PY, Lenz H, et al.: A phase I pharmacokinetic (PK) study of the epothilone B analogue, ixabepilone (BMS-247550) in patients (pts) with advanced malignancies and varying degrees of hepatic impairment. A SWOG Early Therapeutics Committee and NCI Organ Dysfunction Working Group Trial. [Abstract] J Clin Oncol 24 (Suppl 18): A-2004, 2006.

Reference Type: RESULT

Other Identifiers

U01CA076642

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA016087

Identifier Type: NIH

Identifier Source: secondary_id

View Link

S0355

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA032102

Identifier Type: NIH

Identifier Source: secondary_id

View Link

S0355

Identifier Type: -

Identifier Source: org_study_id