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A Phase I Scientific Exploratory Study of Epothilone B Analog (BMS-247550; NSC #710428) in Patients With Solid Tumors and Gynecological Malignancies


Phase 1
18 Years
N/A
Not Enrolling
Both
Breast Cancer, Ovarian Cancer, Unspecified Adult Solid Tumor, Protocol Specific

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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 CenterNew York, New York  10016
Albert Einstein Clinical Cancer CenterBronx, New York  10461