RATIONALE: Drugs used in chemotherapy, such as doxorubicin and docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of doxorubicin and docetaxel by making the tumor cells more sensitive to the drugs.

PURPOSE: This phase I/II trial is studying the effectiveness of combining oblimersen with doxorubicin and docetaxel in treating women who have metastatic or locally advanced breast cancer.

Condition	Treatment or Intervention	Phase
stage IIIA breast cancer stage IIIB breast cancer stage IIIC breast cancer stage IV breast cancer Male Breast Cancer	Drug: docetaxel  Drug: doxorubicin  Drug: filgrastim  Drug: oblimersen  Drug: pegfilgrastim  Procedure: antisense therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: conventional surgery  Procedure: cytokine therapy  Procedure: neoadjuvant therapy  Procedure: surgery	Phase I Phase II

Further Study Details: 

OBJECTIVES: Phase I (completed as of 8/16/04):

• Determine the pharmacokinetics of oblimersen, doxorubicin, and docetaxel in patients with metastatic or locally advanced breast cancer.
• Determine the maximum tolerated dose (MTD) of oblimersen in combination with doxorubicin and docetaxel in these patients.
• Determine the safety of this regimen in these patients.

Phase II:

• Determine the therapeutic efficacy of this regimen at the MTD of oblimersen in a neoadjuvant setting, in terms of pathologic complete response rate, in patients with locally advanced breast cancer.
• Determine the clinical and imaging response in the breast and axillary lymph nodes of patients treated with this regimen.
• Determine the disease-free survival of patients treated with this regimen.
• Determine the role of Bcl-2 expression as a predictor of response to this regimen in these patients.

OUTLINE: This is an open-label, dose-escalation study of oblimersen.

• Patients receive oblimersen IV continuously on days 1-6 interrupted only to administer doxorubicin IV over 15 minutes and docetaxel IV over 60 minutes on day 6. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 7-13 or pegfilgrastim SC on day 7. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of oblimersen 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.
• Phase II: Patients receive doxorubicin, docetaxel, G-CSF or pegfilgrastim, and oblimersen at the MTD as in phase I. Patients with resectable tumors after 6 courses undergo surgical resection.

Patients are followed every 3-6 months for 5 years.

PROJECTED ACCRUAL: A total of 69 patients (9 patients for phase I [phase I portion of the study completed as of 8/16/04] and 60 patients for phase II) will be accrued for this study within 2 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer meeting 1 of the following staging criteria:
• Stage IIIB, IIIC, or IV, including T4, any N, M0; any T, N3, M0; or any T, any N, M1 (phase I) (completed as of 8/16/04)
• Stage IIIA, IIIB, or IIIC, including T4, any N, M0; any T, N2-3, M0; or T3, N1, M0 (phase II)
• Ipsilateral supraclavicular lymph node metastases allowed
• No distant metastases (stage IV)
• Measurable disease by physical exam, mammography, or ultrasound (phase II)
• No known brain metastases
• No symptomatic lymphangitic pulmonary metastases
• No leptomeningeal disease
• Hormone receptor status:
• Not specified

PATIENT CHARACTERISTICS: Age

• 18 and over

Sex

• Male and female

Menopausal status

• Not specified

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 6 months

Hematopoietic

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• ALT no greater than 2.5 times upper limit of normal

Renal

• Creatinine no greater than 2.0 mg/dL

Cardiovascular

• LVEF at least 45% by MUGA and/or echocardiogram
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No grade 2 or greater neuropathy
• No prior allergic reaction attributed to compounds of similar chemical or biological composition to oblimersen or other agents in this study
• No known hypersensitivity to drugs formulated in polysorbate-80
• No ongoing or active infection
• No other concurrent uncontrolled illness
• No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered (phase I) (phase I portion of the study completed as of 8/16/04)
• No more than 3 prior chemotherapy regimens for breast cancer (either as adjuvant or neoadjuvant therapy or for metastatic disease) (phase I) (phase I portion of the study completed as of 8/16/04)
• No prior taxane
• No prior anthracycline
• No prior chemotherapy for breast cancer (phase II)

Endocrine therapy

• No prior hormone therapy for breast cancer

Radiotherapy

• More than 4 weeks since prior radiotherapy and recovered (phase I)
• No prior radiotherapy for breast cancer (phase II)

Surgery

• No prior surgery for breast cancer (phase II)
• No prior definitive surgery for breast cancer

Other

• No prior oblimersen
• No other concurrent anticancer investigational or commercial agents or therapies

Texas
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030-4009,  United States; Recruiting

Study chairs or principal investigators

Francisco J. Esteva, MD,  Study Chair,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000305817; MDA-DM-02700; NCI-6023; NCT00063934
Record last reviewed:  December 2004
Last Updated:  February 7, 2005
Record first received:  July 8, 2003
ClinicalTrials.gov Identifier:  NCT00063934
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08