Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Ixabepilone in Treating Patients With Locally Advanced or Metastatic Breast Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	NCI-02-C-0229 NCI-5791, 5791, NCT00045097

Objectives

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

Entry 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

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

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/mm³
• Platelet count at least 100,000/mm³

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

Expected Enrollment

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

Outcomes

Anti-tumor activity as measured by CT scans and bone scans at baseline and every other course
Ixabepilone toxicity as measured by lab studies at baseline and after every course

Tumor tubulin polymerization and p53 expression from biopsy specimens and cDNA microarray testing at baseline and prior to course 2.
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

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.

Denduluri N, Low JA, Lee JJ, et al.: Phase II trial of ixabepilone, an epothilone B analog, in patients with metastatic breast cancer previously untreated with taxanes. J Clin Oncol 25 (23): 3421-7, 2007.[PUBMED Abstract]

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.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Sandra Swain, MD, Principal investigator(Contact information may not be current)		Ph: 301-496-4345

Registry Information
Official Title		A Phase II Clinical Trial Of BMS-247550 (NSC 710428), An Epothilone B Analog, In Patients With Breast Carcinoma
Trial Start Date		2002-05-22
Registered in ClinicalTrials.gov		NCT00045097
Date Submitted to PDQ		2002-06-19
Information Last Verified		2007-01-08

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