Clinical trial NCT00045097: Ixabepilone in Treating Patients With Locally Advanced or Metastatic Breast Cancer
Official title: A Phase II Clinical Trial Of BMS-247550 (NSC 710428), An Epothilone B Analog, In Patients With Breast Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: male breast cancer
recurrent breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Anti-tumor activity as measured by CT scans and bone scans at baseline and every other course
measure: Ixabepilone toxicity as measured by lab studies at baseline and after every course
Secondary outcomes:
measure: Tumor tubulin polymerization and p53 expression from biopsy specimens and cDNA microarray testing at baseline and prior to course 2.
measure: 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
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Suburban Hospital
state: Maryland
city: Bethesda
country: United States
facility: Oncology Care Associates
state: Maryland
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
state: Maryland
city: Bethesda
country: United States
facility: NCI - Center for Cancer Research
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Sandra M. Swain, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Denduluri N, Low JA, Lee JJ, Berman AW, Walshe JM, Vatas U, Chow CK, Steinberg SM, Yang SX, Swain SM. Phase II trial of ixabepilone, an epothilone B analog, in patients with metastatic breast cancer previously untreated with taxanes. J Clin Oncol. 2007 Aug 10;25(23):3421-7. doi: 10.1200/JCO.2006.10.0784. Epub 2007 Jul 2.
citation: 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.