Clinical trial NCT00049400: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: dose defining
timeFrame: Treatment delays >2 weeks constitute a DLT
Secondary outcomes:
measure: Progression
timeFrame: 30 days after going off study
measure: Symptomatic deterioration
timeFrame: 30 days after going off study
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: Maywood
country: United States
facility: Cardinal Bernardin Cancer Center at Loyola University Medical Center
state: Illinois
city: Kansas City
country: United States
facility: Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
state: Kansas
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Independence
country: United States
facility: Community Oncology Group at Cleveland Clinic Cancer Center
state: Ohio
city: Wooster
country: United States
facility: Cleveland Clinic - Wooster
state: Ohio
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Lackland AFB
country: United States
facility: Wilford Hall Medical Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Bellingham
country: United States
facility: St. Joseph Hospital Community Cancer Center
state: Washington
city: Bremerton
country: United States
facility: Olympic Hematology and Oncology
state: Washington
city: Mt. Vernon
country: United States
facility: Skagit Valley Hospital Cancer Care Center
state: Washington
city: Seattle
country: United States
facility: Group Health Central Hospital
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
state: Washington
city: Seattle
country: United States
facility: University Cancer Center at University of Washington Medical Center
state: Washington
city: Sedro-Wooley
country: United States
facility: North Puget Oncology at United General Hospital
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest - Spokane South
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Medical Center
state: Washington
Study officials:
affiliation: University of California, Davis
name: Angela Davies, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute for Drug Development
name: Chris H. Takimoto, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.