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Treating Patients With Advanced Solid Tumors, Breast Cancer or Recurrent Ovarian Cancer

Phase 1
Completed
Conditions
Breast Cancer
Ovarian Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Interventions
Registration Number
NCT00005807
Lead Sponsor
Albert Einstein College of Medicine
Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of BMS-247550 in treating patients who have metastatic, recurrent, or locally advanced, ovarian cancer, breast cancer, or metastatic or unresectable solid tumors.

Detailed Description

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 Multi-Drug Resistance Gene (MDR1), Multidrug Resistance-associated Protein (MRP) Gene, and canalicular multispecific organic anion transporter 1(cMOAT) messenger ribonucleic acid (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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
40
Inclusion Criteria
  • Histologically or cytologically confirmed metastatic or unresectable solid malignancy for which no standard or curative therapies exist or are no longer effective
  • Metastatic, recurrent, or locally advanced breast, ovarian, or other cancer
  • 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
  • Bilirubin normal
  • AST/ALT no greater than 3 times upper limit of normal
  • Gilbert's syndrome allowed
  • Creatinine no greater than 2 mg/dL
Exclusion Criteria
  • symptomatic congestive heart failure
  • unstable angina pectoris
  • cardiac arrhythmia
  • grade 2 or greater clinical neuropathy
  • prior allergy or hypersensitivity reaction (grade 2 or greater) to prior paclitaxel or other therapy containing Cremophor EL
  • allergy or intolerance to steroids, diphenhydramine, cimetidine, or ranitidine
  • uncontrolled concurrent illness
  • active infection
  • pregnant or nursing
  • other concurrent anticancer therapies or commercial agents
  • other concurrent investigational agents
  • other concurrent highly active antiretroviral therapy for HIV-positive patients

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treated ParticipantsBMS-247550dose escalation treatment
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (2)

NYU School of Medicine's Kaplan Comprehensive Cancer Center

🇺🇸

New York, New York, United States

Albert Einstein Clinical Cancer Center

🇺🇸

Bronx, New York, United States

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