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

Sponsor

Southwest Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00049400

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

Duration (Months)

3.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma Small Intestine Cancer Unspecified Adult Solid Tumor, Protocol Specific	Drug: BMS-247550	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

78 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Oct 1, 2003

Actual Primary Completion Date :

Sep 1, 2006

Actual Study Completion Date :

Dec 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: treatment Single-arm, dose-escalation of BMS-247550	Drug: BMS-247550 BMS-247550 as a 3-hour infusion on Day 1 of a three-week cycle

Arm

Intervention/Treatment

Experimental: treatment

Single-arm, dose-escalation of BMS-247550

Drug: BMS-247550

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

Outcome Measures

Primary Outcome Measures

dose defining [Treatment delays >2 weeks constitute a DLT]

Secondary Outcome Measures

Progression [30 days after going off study]
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 [30 days after going off study]
Global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000
2	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90089-9181
3	University of California Davis Cancer Center	Sacramento	California	United States	95817
4	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois	United States	60153
5	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
6	Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106
7	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
8	Community Oncology Group at Cleveland Clinic Cancer Center	Independence	Ohio	United States	44131
9	Cleveland Clinic - Wooster	Wooster	Ohio	United States	44691
10	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234
11	Wilford Hall Medical Center	Lackland AFB	Texas	United States	78236
12	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229-3900
13	St. Joseph Hospital Community Cancer Center	Bellingham	Washington	United States	98225
14	Olympic Hematology and Oncology	Bremerton	Washington	United States	98310
15	Skagit Valley Hospital Cancer Care Center	Mt. Vernon	Washington	United States	98273
16	Group Health Central Hospital	Seattle	Washington	United States	98104-1387
17	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98104
18	Harborview Medical Center	Seattle	Washington	United States	98104
19	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington	United States	98122-4307
20	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195-6043
21	North Puget Oncology at United General Hospital	Sedro-Wooley	Washington	United States	98284
22	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
23	Wenatchee Valley Medical Center	Wenatchee	Washington	United States	98801-2028

Sponsors and Collaborators

Southwest Oncology Group
National Cancer Institute (NCI)

Investigators

Principal Investigator: Angela Davies, MD, University of California, Davis
Principal Investigator: Chris H. Takimoto, MD, PhD, Institute for Drug Development