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

Primary Purpose

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

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
BMS-247550
Sponsored by
SWOG Cancer Research Network
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring 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 Hodgkin lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult T-cell leukemia/lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent grade 1, 2, or 3 follicular lymphoma, recurrent mantle cell lymphoma, small intestine lymphoma, stage IV adult diffuse large cell or mixed cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult Burkitt lymphoma or 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, 2, or 3 follicular lymphoma, stage IV mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, stage IV marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of MALT, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, recurrent adult Burkitt lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • City of Hope Comprehensive Cancer Center
  • USC/Norris Comprehensive Cancer Center and Hospital
  • University of California Davis Cancer Center
  • Cardinal Bernardin Cancer Center at Loyola University Medical Center
  • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
  • Case Comprehensive Cancer Center
  • Cleveland Clinic Taussig Cancer Center
  • Community Oncology Group at Cleveland Clinic Cancer Center
  • Cleveland Clinic - Wooster
  • Brooke Army Medical Center
  • Wilford Hall Medical Center
  • University of Texas Health Science Center at San Antonio
  • St. Joseph Hospital Community Cancer Center
  • Olympic Hematology and Oncology
  • Skagit Valley Hospital Cancer Care Center
  • Group Health Central Hospital
  • Fred Hutchinson Cancer Research Center
  • Harborview Medical Center
  • Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
  • University Cancer Center at University of Washington Medical Center
  • North Puget Oncology at United General Hospital
  • Cancer Care Northwest - Spokane South
  • Wenatchee Valley Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

treatment

Arm Description

Single-arm, dose-escalation of BMS-247550

Outcomes

Primary Outcome Measures

dose defining

Secondary Outcome Measures

Progression
20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline.
Symptomatic deterioration
Global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.

Full Information

First Posted
November 12, 2002
Last Updated
April 1, 2015
Sponsor
SWOG Cancer Research Network
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00049400
Brief Title
S0355 Ixabepilone in Treating Patients With Advanced Solid Tumors or Lymphomas and Liver Dysfunction
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
October 2003 (undefined)
Primary Completion Date
September 2006 (Actual)
Study Completion Date
December 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
SWOG Cancer Research Network
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Small Intestine Cancer, Unspecified Adult Solid Tumor, Protocol Specific
Keywords
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 Hodgkin lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult T-cell leukemia/lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent grade 1, 2, or 3 follicular lymphoma, recurrent mantle cell lymphoma, small intestine lymphoma, stage IV adult diffuse large cell or mixed cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult Burkitt lymphoma or 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, 2, or 3 follicular lymphoma, stage IV mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, stage IV marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of MALT, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, recurrent adult Burkitt lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
78 (Actual)

8. Arms, Groups, and Interventions

Arm Title
treatment
Arm Type
Experimental
Arm Description
Single-arm, dose-escalation of BMS-247550
Intervention Type
Drug
Intervention Name(s)
BMS-247550
Intervention Description
BMS-247550 as a 3-hour infusion on Day 1 of a three-week cycle
Primary Outcome Measure Information:
Title
dose defining
Time Frame
Treatment delays >2 weeks constitute a DLT
Secondary Outcome Measure Information:
Title
Progression
Description
20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline.
Time Frame
30 days after going off study
Title
Symptomatic deterioration
Description
Global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.
Time Frame
30 days after going off study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Angela Davies, MD
Organizational Affiliation
University of California, Davis
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Chris H. Takimoto, MD, PhD
Organizational Affiliation
Institute for Drug Development
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Comprehensive Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010-3000
Country
United States
Facility Name
USC/Norris Comprehensive Cancer Center and Hospital
City
Los Angeles
State/Province
California
ZIP/Postal Code
90089-9181
Country
United States
Facility Name
University of California Davis Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Cardinal Bernardin Cancer Center at Loyola University Medical Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160-7357
Country
United States
Facility Name
Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Cleveland Clinic Taussig Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Community Oncology Group at Cleveland Clinic Cancer Center
City
Independence
State/Province
Ohio
ZIP/Postal Code
44131
Country
United States
Facility Name
Cleveland Clinic - Wooster
City
Wooster
State/Province
Ohio
ZIP/Postal Code
44691
Country
United States
Facility Name
Brooke Army Medical Center
City
Fort Sam Houston
State/Province
Texas
ZIP/Postal Code
78234
Country
United States
Facility Name
Wilford Hall Medical Center
City
Lackland AFB
State/Province
Texas
ZIP/Postal Code
78236
Country
United States
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229-3900
Country
United States
Facility Name
St. Joseph Hospital Community Cancer Center
City
Bellingham
State/Province
Washington
ZIP/Postal Code
98225
Country
United States
Facility Name
Olympic Hematology and Oncology
City
Bremerton
State/Province
Washington
ZIP/Postal Code
98310
Country
United States
Facility Name
Skagit Valley Hospital Cancer Care Center
City
Mt. Vernon
State/Province
Washington
ZIP/Postal Code
98273
Country
United States
Facility Name
Group Health Central Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104-1387
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Harborview Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122-4307
Country
United States
Facility Name
University Cancer Center at University of Washington Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195-6043
Country
United States
Facility Name
North Puget Oncology at United General Hospital
City
Sedro-Wooley
State/Province
Washington
ZIP/Postal Code
98284
Country
United States
Facility Name
Cancer Care Northwest - Spokane South
City
Spokane
State/Province
Washington
ZIP/Postal Code
99202
Country
United States
Facility Name
Wenatchee Valley Medical Center
City
Wenatchee
State/Province
Washington
ZIP/Postal Code
98801-2028
Country
United States

12. IPD Sharing Statement

Citations:
Citation
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.
Results Reference
result

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

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