A Phase I Scientific Exploratory Study of Epothilone B Analog (BMS-247550; NSC #710428) in Patients With Solid Tumors and Gynecological Malignancies
18 Years
N/A
Both
Breast Cancer, Ovarian Cancer, Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I Scientific Exploratory Study of Epothilone B Analog (BMS-247550; NSC #710428) in Patients With Solid Tumors and Gynecological Malignancies
OBJECTIVES:
- Determine the maximum tolerated dose, recommended phase II dose, and associated toxic
effects of BMS-247550 in patients with advanced solid tumors.
- Determine the pharmacokinetic and pharmacodynamic relationship of this treatment
regimen in these patients.
- Assess the extent of microtubule bundle and mitotic aster formation and cell cycle
kinetics in peripheral blood mononuclear cells in these patients treated with this
regimen.
- Determine any evidence of antitumor activity of this treatment regimen in these
patients.
- Evaluate the relationship between tumor response and the occurrence of mutation in the
class 1 isotype of B-tubulin and B-tubulin isotype distribution in patients with
advanced or recurrent solid tumors, ovarian cancer, or breast cancer treated with this
regimen.
- Investigate MDR1, MRP, and cMOAT mRNA and protein expression as prognosticators of
tumor response in these patients treated with this regimen.
- Determine the relationship between stathmin expression and phosphorylation status as a
function of response in these patients treated with this regimen.
- Correlate the expression of proapoptotic (p53, bax, bad, and bid) and antiapoptotic
(survivin, inhibitors of apoptotic proteins, bcl-2, and bcl-x) proteins in tumor
samples and/or ascites with response and clinical outcome in these patients treated
with this regimen.
OUTLINE: This is a dose-escalation, multicenter study.
- Part I: Patients with advanced solid tumors receive BMS-247550 IV over 1 hour every 3
weeks. Treatment continues in the absence of disease progression or unacceptable
toxicity.
Cohorts of 3-6 patients receive escalating doses of BMS-247550 until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity.
- Part II: Patients with ovarian, breast, or other cancer receive BMS-247550 as in the
part I portion of the study at the MTD. Treatment continues in the absence of disease
progression or unacceptable toxicity.
Patients are followed at 2 months.
PROJECTED ACCRUAL: Approximately 42-66 patients will be accrued for this study within 12-16
months.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Part I:
- Histologically or cytologically confirmed metastatic or unresectable solid
malignancy for which no standard or curative therapies exist or are no longer
effective
- Part II:
- Metastatic, recurrent, or locally advanced breast, ovarian, or other cancer
- At least 1 site amenable to biopsy
- No known brain metastases
- Hormone receptor status:
- Not specified
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Sex:
- Male or female
Menopausal status:
- Not specified
Performance status:
- ECOG 0-1 OR
- Karnofsky 80-100%
Life expectancy:
- Not specified
Hematopoietic:
- Hemoglobin at least 9.0 g/dL
- WBC at least 3,000/mm3
- Absolute neutrophil count at least 1,500/mm3
- Platelet count at least 100,000/mm3
Hepatic:
- Bilirubin normal
- AST/ALT no greater than 3 times upper limit of normal
- Gilbert's syndrome allowed
Renal:
- Creatinine no greater than 2 mg/dL
Cardiovascular:
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
Other:
- No grade 2 or greater clinical neuropathy
- No prior allergy or hypersensitivity reaction (grade 2 or greater) to prior
paclitaxel or other therapy containing Cremophor EL
- No allergy or intolerance to steroids, diphenhydramine, cimetidine, or ranitidine
- No other uncontrolled concurrent illness
- No active infection
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and
recovered
Endocrine therapy:
- Not specified
Radiotherapy:
- At least 3 weeks since prior radiotherapy
- No prior radiotherapy to more than 35% of bone marrow
- Prior whole pelvic radiotherapy allowed
Surgery:
- See Disease Characteristics
Other:
- No other concurrent anticancer therapies or commercial agents
- No other concurrent investigational agents
- No concurrent highly active antiretroviral therapy for HIV-positive patients
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Franco M. Muggia, MD
Investigator Role:
Study Chair
Investigator Affiliation:
New York University School of Medicine
Authority:
United States: Federal Government
Study ID:
CDR0000067800
NCT ID:
NCT00005807
Start Date:
July 2000
Completion Date:
Related Keywords:
- Breast Cancer
- Ovarian Cancer
- Unspecified Adult Solid Tumor, Protocol Specific
- stage IV breast cancer
- stage IIIA breast cancer
- recurrent breast cancer
- stage IIIB breast cancer
- stage III ovarian epithelial cancer
- stage IV ovarian epithelial cancer
- recurrent ovarian epithelial cancer
- unspecified adult solid tumor, protocol specific
- ovarian stromal cancer
- stage III ovarian germ cell tumor
- stage IV ovarian germ cell tumor
- recurrent ovarian germ cell tumor
- borderline ovarian surface epithelial-stromal tumor
- ovarian sarcoma
- male breast cancer
- Breast Neoplasms
- Ovarian Neoplasms
- Neoplasms
Name | Location |
|---|---|
| NYU School of Medicine's Kaplan Comprehensive Cancer Center | New York, New York 10016 |
| Albert Einstein Clinical Cancer Center | Bronx, New York 10461 |
