Treating Patients With Advanced Solid Tumors, Breast Cancer or Recurrent Ovarian Cancer
Condition: Breast Cancer; Ovarian Cancer; Unspecified Adult Solid Tumor, Protocol Specific
MeSH terms: Breast Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): BMS-247550
Intervention type(s): Drug
Intervention description(s): anticancer agent for the treatment of patients with malignant tumors.
Other intervention name(s): epothilone derivative
Intervention MeSH terms: Epothilones
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: 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