Oblimersen Plus Doxorubicin and Docetaxel in Treating Patients With Metastatic or Locally Advanced Breast Cancer - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00063934

Purpose

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 side effects and best dose of oblimersen when given together with doxorubicin and docetaxel and to see how well they work in treating women with metastatic or locally advanced breast cancer.

Condition	Intervention	Phase
Breast Cancer	Biological: filgrastim Biological: oblimersen sodium Biological: pegfilgrastim Drug: docetaxel Drug: doxorubicin hydrochloride Procedure: conventional surgery Procedure: neoadjuvant therapy	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
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

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Surgery

Drug Information available for: Doxorubicin Doxorubicin hydrochloride Myocet Docetaxel Filgrastim Oblimersen sodium Pegfilgrastim

U.S. FDA Resources

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

Primary Outcome Measures:

Pharmacokinetics as measured by plasma levels of docetaxel, doxorubicin, and oblimersen on days 1-6 in course 1 of treatment [ Designated as safety issue: No ]
Toxicity measured by common toxicity criteria every 3 weeks [ Designated as safety issue: Yes ]
Pathologic complete response measured by microscopic evaluation of tissue specimen at time of definitive surgery (after 6 courses of neoadjuvant therapy) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Clinical imagining response by physical exam and ultrasound measurements of primary tumor and axillary lymph nodes after 3 and 6 courses of treatment [ Designated as safety issue: No ]
Disease free survival yearly [ Designated as safety issue: No ]
Bcl-2 expression in breast cancer tissue by protein and mRNA expression before treatment and at 3-5 days after oblimersen treatment [ Designated as safety issue: No ]

Study Start Date:	May 2003
Primary Completion Date:	February 2008 (Final data collection date for primary outcome measure)

Detailed Description:

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.

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.

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.

Eligibility

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00063934

Locations

United States, Texas
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009

Sponsors and Collaborators

M.D. Anderson Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Francisco J. Esteva, MD

M.D. Anderson Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Moulder SL, Symmans WF, Booser DJ, Madden TL, Lipsanen C, Yuan L, Brewster AM, Cristofanilli M, Hunt KK, Buchholz TA, Zwiebel J, Valero V, Hortobagyi GN, Esteva FJ. Phase I/II study of G3139 (Bcl-2 antisense oligonucleotide) in combination with doxorubicin and docetaxel in breast cancer. Clin Cancer Res. 2008 Dec 1;14(23):7909-16.

Study ID Numbers:	CDR0000305817, MDA-DM-02700, NCI-6023
Study First Received:	July 8, 2003
Last Updated:	April 21, 2009
ClinicalTrials.gov Identifier:	NCT00063934 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
male breast cancer

Additional relevant MeSH terms:

Docetaxel
Neoplasms
Neoplasms by Site
Skin Diseases
Antineoplastic Agents
Therapeutic Uses

Breast Neoplasms
Antibiotics, Antineoplastic
Pharmacologic Actions
Doxorubicin
Breast Diseases

ClinicalTrials.gov processed this record on November 27, 2009