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

Alternate Title

Oblimersen Plus Doxorubicin and Docetaxel in Treating Patients With Metastatic or Locally Advanced Breast Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Completed 18 and over NCI MDA-DM-02700 NCI-6023, NCT00063934, 6023

Objectives

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

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

Phase II:

1. 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.
2. Determine the clinical and imaging response in the breast and axillary lymph nodes of patients treated with this regimen.
3. Determine the disease-free survival of patients treated with this regimen.
4. Determine the role of Bcl-2 expression as a predictor of response to this regimen in these patients.

Entry 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

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

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/mm³
• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

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

Expected Enrollment

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.

Outcomes

Pharmacokinetics as measured by plasma levels of docetaxel, doxorubicin, and oblimersen on days 1-6 in course 1 of treatment
Toxicity measured by common toxicity criteria every 3 weeks
Pathologic complete response measured by microscopic evaluation of tissue specimen at time of definitive surgery (after 6 courses of neoadjuvant therapy)

Clinical imagining response by physical exam and ultrasound measurements of primary tumor and axillary lymph nodes after 3 and 6 courses of treatment
Disease free survival yearly
Bcl-2 expression in breast cancer tissue by protein and mRNA expression before treatment and at 3-5 days after oblimersen treatment

Outline

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

• Phase I (phase I completed as of 8/16/04): 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.

Trial Contact Information

Trial Lead Organizations

M. D. Anderson Cancer Center at University of Texas

Francisco Esteva, MD, Protocol chair		Ph: 713-792-2817; 800-392-1611 Email: festeva@mdanderson.org

Registry Information
Official Title		A Phase I/II Study of Bcl-2 Antisense Oligonucleotide (Genasense) in Combination with Doxorubicin and Docetaxel in Metastatic and Locally Advanced Breast Cancer
Trial Start Date		2003-05-16
Trial Completion Date		2008-02-27
Registered in ClinicalTrials.gov		NCT00063934
Date Submitted to PDQ		2003-05-09
Information Last Verified		2006-01-17
NCI Grant/Contract Number		CM17003, CA16672

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