Ixabepilone in Treating Patients With Locally Advanced or Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00045097
First received: September 6, 2002
Last updated: June 18, 2013
Last verified: January 2007
  Purpose

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

PURPOSE: This phase II trial is studying how well ixabepilone works in treating patients with locally advanced or metastatic breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: ixabepilone
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Clinical Trial Of BMS-247550 (NSC 710428), An Epothilone B Analog, In Patients With Breast Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Anti-tumor activity as measured by CT scans and bone scans at baseline and every other course [ Designated as safety issue: No ]
  • Ixabepilone toxicity as measured by lab studies at baseline and after every course [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Tumor tubulin polymerization and p53 expression from biopsy specimens and cDNA microarray testing at baseline and prior to course 2. [ Designated as safety issue: No ]
  • Neurotoxicity assessment as measured by Semmes-Weinstein monofilament, sharpened Rombrog, one-legged stance, Jebsen Test of hand function, the grooved pef board , and subjective questionnaires at baseline and prior to every other course [ Designated as safety issue: Yes ]

Study Start Date: May 2002
Study Completion Date: July 2007
Detailed Description:

OBJECTIVES:

  • Determine any antitumor activity of ixabepilone, in terms of objective response rate, in patients with incurable, locally advanced or metastatic breast cancer.
  • Determine the toxicity of this drug in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to prior taxane therapy (yes vs no).

Patients (with or without prior taxane exposure) receive ixabepilone IV over 1 hour on days 1-5. An additional cohort of 37 patients who have received prior taxane therapy are then accrued to receive ixabepilone IV over 1 hour on days 1-3 at a higher starting dose. For all patients, courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients who receive more than 6 courses with satisfactory response may be treated every 4-5 weeks.

Patients removed for unacceptable toxicty are followed periodically.

PROJECTED ACCRUAL: A total of 105 patients (at least 74 with and 21 without prior taxane exposure) will be accrued for this study within 26 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed* adenocarcinoma of the breast

    • Incurable, locally advanced or metastatic disease
    • Primarily stage IV disease, but some inoperable stage III disease may be eligible (e.g., a patient with T4 and/or N2-3 disease who cannot receive doxorubicin or who has already received other therapy) NOTE: *Patients with no available tissue for histologic confirmation but who have documentation of breast surgery and prior chemotherapy are eligible upon approval of the principal investigator
  • Measurable disease
  • No evidence of CNS metastases by brain MRI or contrast head CT scan

    • CNS metastases controlled by radiotherapy or surgical resection at least 6 months prior to study enrollment are allowed
  • Hormone receptor status:

    • Not specified

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Sex

  • Female or male

Menopausal status

  • Not specified

Performance status

  • ECOG 0-2

Life expectancy

  • At least 3 months

Hematopoietic

  • Granulocyte count at least 1,200/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic

  • Bilirubin no greater than 1.5 times upper limit of normal (ULN) (3 times ULN if there is clinical evidence of Gilbert's disease)
  • AST and ALT no greater than 2.5 times ULN

Renal

  • Creatinine normal OR
  • Creatinine clearance greater than 40 mL/min

Other

  • No poor medical risk due to other nonmalignant systemic disease
  • No active uncontrolled infection
  • No sensory, motor, or cranial neuropathy or neuropathic pain grade 2 or greater (unless neuropathy is clearly due to underlying breast cancer)
  • No other concurrent serious medical illness
  • No prior severe hypersensitivity reactions to agents containing Cremophor EL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 2 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • More than 4 weeks since prior filgrastim (G-CSF), pegfilgrastim, or thrombopoietin (or other platelet growth factors)
  • No concurrent immunotherapy

Chemotherapy

  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • No other concurrent chemotherapy for breast cancer

Endocrine therapy

  • More than 2 weeks since prior hormonal therapy
  • No concurrent hormonal therapy

Radiotherapy

  • See Disease Characteristics
  • No prior craniospinal radiation
  • No prior total body irradiation
  • More than 4 weeks since prior radiotherapy

Surgery

  • See Disease Characteristics

Other

  • No other concurrent investigational drugs
  • No concurrent cytochrome p450 3A4 inhibitors, including any of the following:

    • Clarithromycin
    • Erythromycin
    • Troleandomycin
    • Delaviridine
    • Nelfinavir
    • Amprenavir
    • Ritonavir
    • Indinavir
    • Saquinavir
    • Lopinavir
    • Itraconazole
    • Ketoconazole
    • Fluconazole (> 200 mg/day)
    • Voriconazole
    • Nefazodone
    • Fluvoxamine
    • Verapamil
    • Diltiazem
    • Amiodarone
  • Concurrent bisphosphonates for bone metastases allowed
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00045097

Locations
United States, Maryland
NCI - Center for Cancer Research
Bethesda, Maryland, United States, 20892
Oncology Care Associates
Bethesda, Maryland, United States, 20817
Suburban Hospital
Bethesda, Maryland, United States, 20814
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
Investigators
Principal Investigator: Sandra M. Swain, MD National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Low J, Croarkin E, Parks R, et al.: Assessment of neurotoxicity in patients receiving BMS-247550 for metastatic breast cancer. [Abstract] Breast Cancer Research and Treatment 85.2: A-358, 2004. Also available online. Last accessed April 22, 2004.

ClinicalTrials.gov Identifier: NCT00045097     History of Changes
Obsolete Identifiers: NCT00040079
Other Study ID Numbers: CDR0000256355, NCI-02-C-0229, NCI-5791
Study First Received: September 6, 2002
Last Updated: June 18, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
male breast cancer
recurrent breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on April 16, 2014