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Oblimersen Plus Doxorubicin and Docetaxel in Treating Patients With Metastatic or Locally Advanced Breast Cancer
This study has been completed.

First Received on July 8, 2003.   Last Updated on July 5, 2010   History of Changes
Sponsor: M.D. Anderson Cancer Center
Collaborator: National Cancer Institute (NCI)
Information provided by: M.D. Anderson Cancer Center
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
Radiation: Oblimersen Sodium
Biological: Pegfilgrastim
Drug: Docetaxel
Drug: Doxorubicin Hydrochloride
Procedure: Conventional Surgery
Procedure: Neoadjuvant Therapy
 Phase I
Phase II

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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
Drug Information available for: Doxorubicin Doxorubicin hydrochloride Docetaxel Filgrastim Lenograstim Granulocyte colony-stimulating factor Oblimersen sodium Pegfilgrastim
U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Pharmacokinetics [ Time Frame: Days 1-6 in course 1 of 21-day treatment ] [ Designated as safety issue: No ]
    Pharmacokinetics as measured by plasma levels of docetaxel, doxorubicin, and oblimersen

  • Patient Toxicity [ Time Frame: Every 3 weeks ] [ Designated as safety issue: Yes ]
    Toxicity measured by common toxicity criteria every 3 weeks

  • Number of Patients with Pathologic Complete Response (pCR) [ Time Frame: At time of definitive surgery (after 6 courses of neoadjuvant therapy) ] [ Designated as safety issue: No ]
    pathologic complete response (pCR) rate measured by microscopic evaluation of tissue specimen Pathologic complete response measured by microscopic evaluation of tissue specimen at time of definitive surgery (after 6 courses of neoadjuvant therapy)


Secondary Outcome Measures:
  • Clinical Imaging Response [ Time Frame: After 3 and 6 courses of treatment ] [ Designated as safety issue: No ]
    Clinical imaging response by physical exam and ultrasound measurements of primary tumor and axillary lymph nodes after 3 and 6 courses of treatment

  • Number of Patients with Disease Free Survival [ Time Frame: Annually ] [ Designated as safety issue: No ]
  • Bcl-2 Expression in Breast Cancer Tissue [ Time Frame: before treatment and at 3-5 days after oblimersen treatment ] [ 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


Enrollment: 31
Study Start Date: May 2003
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oblimersen Plus Doxorubicin + Docetaxel Biological: Filgrastim
300 mcg subcutaneously (SC) on days 7-13 or pegfilgrastim SC on day 7.
Other Names:
  • Neupogen
  • G-CSF
Radiation: Oblimersen Sodium
7 mg/kg/day IV (by vein) continuously on days 1-6 interrupted only to administer doxorubicin IV over 15 minutes and docetaxel IV over 60 minutes on day 6.
Other Names:
  • Genasense
  • G3139
Biological: Pegfilgrastim
6 mg subcutaneously (SC) on day 7 of 21-day cycle or Filgrastim SC on days 7-13.
Other Names:
  • PEG-G-CSF
  • Neulasta
Drug: Docetaxel
Day 6, 75 mg/m^2 (infused over 60 minutes)
Other Name: Taxotere
Drug: Doxorubicin Hydrochloride
Day 6, 50 mg/m^2 (infused over 15 minutes)
Other Names:
  • Adriamycin PFS
  • Adriamycin RDF
Procedure: Conventional Surgery
For resectable tumors surgical resection after 6 courses.
Procedure: Neoadjuvant Therapy

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

Inclusion Criteria:

  1. Patients must have histologically or cytologically confirmed breast cancer.
  2. To be eligible for the phase I component of this study, patients must have stage IIIB, IIIC or IV breast cancer. These include patients with T4, any N, M0; any T, N3, M0; any T, any N, M1.
  3. To be eligible for the phase II component, patients must have stage IIIA, IIIB, or IIIC breast cancer. These include patients with T4, any N, M0; any T, N2-3, M0; T3, N1, M0. Patients with ipsilateral supraclavicular lymph node metastases (IIIC) are eligible. Patients with evidence of distant metastases (stage IV) are not eligible.
  4. Measurable disease is not required for patients participating in the phase I component. Measurable disease is required for the phase II component.
  5. Prior G3139, taxane or anthracycline therapy is not allowed.
  6. Life expectancy of greater than 6 months.
  7. ECOG performance status 0, 1, or 2 (Karnofsky >60%; see Appendix A).
  8. Patients must have normal organ and marrow function, as defined in the protocol.
  9. Normal cardiac function (LVEF 45% or greater) as documented by MUGA scan and/or echocardiogram.

Exclusion Criteria:

  1. Patients with metastatic breast cancer participating in the phase I component may not have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the phase I study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
  2. For patients with locally advanced breast cancer participating in the phase II component may not have received any chemotherapy for breast cancer.
  3. Patients may not be receiving any other investigational agents.
  4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to G3139 or other agents used in the study. Patients are excluded if known hypersensitivity to drugs formulated in polysorbate 80 (Tween 80).
  5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  6. Patients with neuropathy grade 2 or higher.
  7. Pregnant women are excluded from this study because G3139 is an oligonucleotide agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with G3139, breastfeeding should be discontinued if the mother is treated with G3139. These potential risks may also apply to other agents used in this study, such as doxorubicin and docetaxel.
  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
UT MD Anderson Cancer Center Website  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.

Responsible Party: Francisco J. Esteva, MD, PHD / Professor, UT MD Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00063934     History of Changes
Other Study ID Numbers: DM02-700, P30CA016672, MDA-DM-02700, NCI-6023, CDR0000305817
Study First Received: July 8, 2003
Last Updated: July 5, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
male breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Doxorubicin
Docetaxel
Lenograstim
 Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 09, 2012



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