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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00049400
First received: November 12, 2002
Last updated: February 12, 2013
Last verified: February 2013
  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: BMS-247550
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: 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

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • dose defining [ Designated as safety issue: Yes ]

Enrollment: 78
Study Start Date: October 2003
Study Completion Date: December 2007
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: treatment Drug: BMS-247550
BMS-247550 as a 3-hour infusion on Day 1 of a three-week cycle

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90089-9181
University of California Davis Cancer Center
Sacramento, California, United States, 95817
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 Taussig Cancer Center
Cleveland, Ohio, United States, 44195
Community Oncology Group at Cleveland Clinic Cancer Center
Independence, Ohio, United States, 44131
Cleveland Clinic - Wooster
Wooster, Ohio, United States, 44691
United States, Texas
Brooke Army Medical Center
Fort Sam Houston, Texas, United States, 78234
Wilford Hall Medical Center
Lackland AFB, Texas, United States, 78236
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229-3900
United States, Washington
St. Joseph Hospital Community Cancer Center
Bellingham, Washington, United States, 98225
Olympic Hematology and Oncology
Bremerton, Washington, United States, 98310
Skagit Valley Hospital Cancer Care Center
Mt. Vernon, Washington, United States, 98273
Group Health Central Hospital
Seattle, Washington, United States, 98104-1387
Harborview Medical Center
Seattle, Washington, United States, 98104
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98104
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
North Puget Oncology at United General Hospital
Sedro-Wooley, Washington, United States, 98284
Cancer Care Northwest - Spokane South
Spokane, Washington, United States, 99202
Wenatchee Valley Medical Center
Wenatchee, Washington, United States, 98801-2028
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Principal Investigator: Angela Davies, MD University of California, Davis
Principal Investigator: Chris H. Takimoto, MD, PhD, FACP Institute for Drug Development
  More Information

Additional Information:
Publications:
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.

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00049400     History of Changes
Other Study ID Numbers: CDR0000258060, U01CA076642, P30CA016087, S0355, U10CA032102
Study First Received: November 12, 2002
Last Updated: February 12, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Southwest Oncology Group:
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

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Large-Cell, Immunoblastic
Liver Diseases
Duodenal Neoplasms
Ileal Neoplasms
Jejunal Neoplasms
Intestinal Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Digestive System Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Gastrointestinal Diseases
Duodenal Diseases
Intestinal Diseases
Ileal Diseases
Jejunal Diseases

ClinicalTrials.gov processed this record on July 28, 2014