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Ixabepilone in Treating Patients With Advanced Solid Tumors or Lymphomas and Liver Dysfunction
This study is ongoing, but not recruiting participants.
Sponsors and Collaborators: Southwest Oncology Group
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00049400
  Purpose

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.


Condition Intervention Phase
Lymphoma
Small Intestine Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: ixabepilone
Phase I

MedlinePlus related topics: Cancer Intestinal Cancer Lymphoma
Drug Information available for: Epothilone B Ixabepilone
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: A Phase I Pharmacokinetic Study Of Epothilone B Analogue BMS-247550 (NSC 710428D) In Patients With Advanced Malignancies And Varying Levels Of Liver Dysfunction

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment: 84
Study Start Date: October 2003
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00049400

Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
University of California Davis Cancer Center
Sacramento, California, United States, 95817
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90089-9181
United States, Illinois
Cardinal Bernardin Cancer Center at Loyola University Medical Center
Maywood, Illinois, United States, 60153
United States, Kansas
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
Kansas City, Kansas, United States, 66160-7357
United States, Ohio
Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106
Cleveland Clinic - Wooster
Wooster, Ohio, United States, 44691
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
Community Oncology Group at Cleveland Clinic Cancer Center
Independence, Ohio, United States, 44131
United States, Texas
Brooke Army Medical Center
Fort Sam Houston, Texas, United States, 78234
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229-3900
Wilford Hall Medical Center
Lackland AFB, Texas, United States, 78236
United States, Washington
Cancer Care Northwest - Spokane South
Spokane, Washington, United States, 99202
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98104
Group Health Central Hospital
Seattle, Washington, United States, 98104-1387
Harborview Medical Center
Seattle, Washington, United States, 98104
North Puget Oncology at United General Hospital
Sedro-Wooley, Washington, United States, 98284
Wenatchee Valley Medical Center
Wenatchee, Washington, United States, 98801-2028
Skagit Valley Hospital Cancer Care Center
Mt. Vernon, Washington, United States, 98273
St. Joseph Hospital Community Cancer Center
Bellingham, Washington, United States, 98225
Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
Seattle, Washington, United States, 98122-4307
University Cancer Center at University of Washington Medical Center
Seattle, Washington, United States, 98195-6043
Olympic Hematology and Oncology
Bremerton, Washington, United States, 98310
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Investigator: Angela Davies, MD University of California, Davis
Investigator: Chris H. Takimoto, MD, PhD, FACP Institute for Drug Development
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications of Results:
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.

Study ID Numbers: CDR0000258060, SWOG-S0355, NCI-5707, NYU-0132
Study First Received: November 12, 2002
Last Updated: July 23, 2008
ClinicalTrials.gov Identifier: NCT00049400  
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
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 diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult Burkitt lymphoma
recurrent adult Hodgkin lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult T-cell leukemia/lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
small intestine lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult Burkitt lymphoma
stage IV adult 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 follicular lymphoma
stage IV grade 2 follicular lymphoma

Study placed in the following topic categories:
Liver Diseases
Lymphoma, Mantle-Cell
Hodgkin lymphoma, adult
Lymphoma, small cleaved-cell, diffuse
Ileal Diseases
Lymphoma, large-cell, immunoblastic
Central nervous system lymphoma, primary
Duodenal Neoplasms
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Large-Cell, Anaplastic
Hodgkin Disease
Chronic lymphocytic leukemia
Epothilone B
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Digestive System Neoplasms
Leukemia, B-cell, chronic
B-cell lymphomas
Leukemia, T-Cell
Gastrointestinal Neoplasms
Anaplastic large cell lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell, Cutaneous
Hodgkin's disease
Gastrointestinal Diseases
Cutaneous T-cell lymphoma
Lymphoma, Follicular
Lymphoma, B-Cell, Marginal Zone
Lymphoma, B-Cell
Lymphoma, large-cell

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Antineoplastic Agents
Jejunal Diseases
Therapeutic Uses
Mitosis Modulators
Tubulin Modulators
Antimitotic Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009