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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00049400
• Other study ID #: S0355
• Secondary ID: U01CA076642P30CA
• Status: Completed
• Phase: Phase 1
• First received: November 12, 2002
• Last updated: April 1, 2015
• Start date: October 2003
• Est. completion date: December 2007

Study information

• Verified date: April 2015
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: December 2007
• Est. primary completion date: September 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
United States	St. Joseph Hospital Community Cancer Center	Bellingham	Washington
United States	Olympic Hematology and Oncology	Bremerton	Washington
United States	Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Community Oncology Group at Cleveland Clinic Cancer Center	Independence	Ohio
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Wilford Hall Medical Center	Lackland AFB	Texas
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Skagit Valley Hospital Cancer Care Center	Mt. Vernon	Washington
United States	University of California Davis Cancer Center	Sacramento	California
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Group Health Central Hospital	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-Wooley	Washington
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Wenatchee Valley Medical Center	Wenatchee	Washington
United States	Cleveland Clinic - Wooster	Wooster	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 an

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	dose defining		Treatment delays >2 weeks constitute a DLT	Yes
Secondary	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.	30 days after going off study	No
Secondary	Symptomatic deterioration	Global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.	30 days after going off study	Yes