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A Phase I Pharmacokinetic Study Of Epothilone B Analogue BMS-247550 (NSC 710428D) In Patients With Advanced Malignancies And Varying Levels Of Liver Dysfunction


Phase 1
18 Years
N/A
Not Enrolling
Both
Lymphoma, Small Intestine Cancer, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Pharmacokinetic Study Of Epothilone B Analogue BMS-247550 (NSC 710428D) In Patients With Advanced Malignancies And Varying Levels Of Liver Dysfunction


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

dose defining

Safety Issue:

Yes

Principal Investigator

Angela Davies, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of California, Davis

Authority:

United States: Federal Government

Study ID:

CDR0000258060

NCT ID:

NCT00049400

Start Date:

October 2003

Completion Date:

December 2007

Related Keywords:

  • Lymphoma
  • Small Intestine Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • 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
  • stage IV grade 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 mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large-Cell, Immunoblastic
  • Liver Diseases
  • Duodenal Neoplasms
  • Ileal Neoplasms
  • Jejunal Neoplasms
  • Intestinal Neoplasms

Name

Location

Fred Hutchinson Cancer Research Center Seattle, Washington  98109
Cardinal Bernardin Cancer Center at Loyola University Medical Center Maywood, Illinois  60153-5500
University of Texas Health Science Center at San Antonio San Antonio, Texas  78284-7811
Case Comprehensive Cancer Center Cleveland, Ohio  44106-5065
Cleveland Clinic Taussig Cancer Center Cleveland, Ohio  44195
USC/Norris Comprehensive Cancer Center and Hospital Los Angeles, California  90033-0804
Brooke Army Medical Center Fort Sam Houston, Texas  78234-6200
University of California Davis Cancer Center Sacramento, California  95817
City of Hope Comprehensive Cancer Center Duarte, California  91010
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center Kansas City, Kansas  66160-7353
Swedish Cancer Institute at Swedish Medical Center - First Hill Campus Seattle, Washington  98104
Wilford Hall Medical Center Lackland Air Force Base, Texas  78236-5300
St. Joseph Hospital Community Cancer Center Bellingham, Washington  98225
Olympic Hematology and Oncology Bremerton, Washington  98310
Skagit Valley Hospital Cancer Care Center Mt. Vernon, Washington  98273
University Cancer Center at University of Washington Medical Center Seattle, Washington  98195
Harborview Medical Center Seattle, Washington  98104
Group Health Central Hospital Seattle, Washington  98104
North Puget Oncology at United General Hospital Sedro-Wooley, Washington  98284
Cancer Care Northwest - Spokane South Spokane, Washington  99202
Community Oncology Group at Cleveland Clinic Cancer Center Independence, Ohio  44131
Cleveland Clinic - Wooster Wooster, Ohio  44691
Wenatchee Valley Medical Center Wenatchee, Washington  98801-2028