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Therapy With Docetaxel and ZD1839 for Patients Who Have Advanced Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by:
NSABP Foundation Inc
ClinicalTrials.gov Identifier:
NCT00052169
First received: January 24, 2003
Last updated: December 13, 2007
Last verified: December 2007
  Purpose

The purpose of this study is to learn how breast cancer tumors respond to treatment combining the drugs docetaxel and ZD1839.


Condition Intervention Phase
Breast Neoplasms
Drug: ZD1839 in combination with docetaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Multi-Center Trial of ZD1839 (IRESSA) in Combination With Docetaxel as First-Line Treatment in Patients With Advanced Breast Cancer

Resource links provided by NLM:


Further study details as provided by NSABP Foundation Inc:

Primary Outcome Measures:
  • To estimate the clinical benefit rate of the combination of ZD 1839 and docetaxel; clinical benefit measured by clinical response, pathologic response, and stable disease (SD greater than or equal to 24 weeks) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To characterize the safety profile of the combination of ZD 1839 and docetaxel as measured by the frequency and severity of adverse events. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To estimate the duration of clinical benefit. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To estimate the objective tumor response rate (using RECIST best overall response of CR + PR). [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To estimate the duration of tumor response. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To estimate progression-free survival. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To estimate time to treatment failure by measuring time to treatment failure (includes disease progression, second primary cancer, death from any cause, or discontinuation of protocol therapy in the absence of disease progression). [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 33
Study Start Date: January 2003
Study Completion Date: September 2006
Intervention Details:
    Drug: ZD1839 in combination with docetaxel
    Docetaxel given as 75 mg/m2 IV every 3 weeks combined with ZD1839 (IRESSA) 250 mg orally daily until disease progression or withdrawal criteria are met.
    Other Names:
    • Docetaxel (Taxotere)
    • ZD1839, gefitinib (Iressa)
Detailed Description:

Patients with advanced breast cancer continue to have an extremely poor prognosis with an average life expectancy of approximately 2 years. Novel treatments designed to exploit biologic properties of the tumor are urgently required as a means to improve the outcome for the large numbers of patients who relapse after receiving optimal chemotherapy treatments.

Overexpresssion of EGFR and/or TGF-alpha is frequent in human breast cancer and has been correlated in many cases with poor prognostic features. Inhibition of the EGFR pathway has been proposed as a potential therapeutic modality in advanced breast cancer. The antiproliferative activity of ZD 1839 in combination with cytotoxic drugs, such as docetaxel was evaluated in breast cancer cell lines ZR-75-1 and MCF-10A ras that coexpress EGFR and TGF-alpha. Combination treatment demonstrated dose dependent supra-additive growth inhibition and markedly enhanced apoptotic cell death.

Although taxanes bind to the microtubular network in cells that is essential for mitotic and interphase cellular functions, the mechanism by which these agents induce cell death is not entirely clear. Docetaxel has also shown dose-dependent anti-angiogenic activity. Thus, the mechanism(s) of anti-tumor activity of docetaxel remain unclear and combinations of signal transduction pathway inhibition and/or anti-angiogenesis may provide potentiation of concurrent ZD 1839 and docetaxel therapy.

This phase 2 trial is designed to prospectively investigate the efficacy and safetey of combination therapy with ZD 1839 and docetaxel in patients with metastatic breast cancer.

  Eligibility

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

Inclusion Criteria

  • Histologic confirmation of breast cancer
  • Signed consent
  • Current diagnosis of metastatic breast cancer
  • At least one uni-dimensionally measurable lesion with clearly defined margins
  • Patients taking bisphosphonates for documented prior bone metastasis may be included
  • Patients may have received prior adjuvant chemotherapy including an anthracycline and/or an alkylating agent. Patients may have received prior paclitaxel or trastuzumab for adjuvant therapy. Patients may not have received prior docetaxel treatment
  • Patients may have received unlimited prior hormonal therapy regimens for metastatic disease or adjuvant therapy and must have documentation of progressive disease prior to entry. Hormonal therapy must be discontinued at least 2 weeks prior to study entry
  • Patients may have received prior radiation therapy provided it was completed at least 2 weeks before study entry. Prior radiotherapy to treat bone metastasis or spinal cord compression is permitted provided it was completed prior to study entry
  • Zubrod performance status 0, 1, or 2
  • Life expectancy of 12 weeks or more in opinion of investigator
  • LVEF greater than or equal to LLN without clinical signs or symptoms of heart failure
  • adequate bone marrow, hepatic, and renal function

Ineligibility Criteria

  • Prior ZD1839 or other anti EGFR or small molecule TKI
  • Previous or concurrent chemo or Herceptin for metastatic breast cancer
  • Unresolved non-permanent major end organ chronic toxicity from previous anticancer therapy greater than CTC grade 2
  • Radiation therapy less than 14 days before study entry, with exception of RT to treat bone metastasis or spinal cord compression
  • Incomplete healing of surgical incision from previous major surgery
  • Newly diagnosed (within 12 weeks) intracerebral metastases
  • Signs of neurological symptoms consistent with new onset spinal cord compression
  • Evidence of severe or uncontrolled systemic disease
  • Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for patient to participate
  • Pregnancy or breast feeding
  • Patients who are currently using contact lenses. Patients who discontinue wearing contact lenses prior to study entry are eligible.
  • Patients with untreated ocular inflammation or infection
  • Patients with contraindications to corticosteroid use
  • History of another malignancy within past 5 years that could confound diagnosis or staging of breast cancer
  • Patients receiving other investigational drugs
  • Previous docetaxel treatment
  • Patients currently taking systemic retinoids or herbal medicines
  • Patients currently taking drugs known to induce Cyt P4503A4
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00052169

Locations
United States, Pennsylvania
NSABP Operations Center
Pittsburgh, Pennsylvania, United States, 15212
Sponsors and Collaborators
NSABP Foundation Inc
AstraZeneca
Investigators
Principal Investigator: Norman Wolmark, MD NSABP Foundation Inc
  More Information

Publications:
Responsible Party: Norman Wolmark, MD/Chairman, NSABP Foundation Inc., NSABP Foundation, Inc.
ClinicalTrials.gov Identifier: NCT00052169     History of Changes
Other Study ID Numbers: NSABP FB-IR-002
Study First Received: January 24, 2003
Last Updated: December 13, 2007
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by NSABP Foundation Inc:
metastatic breast cancer
docetaxel
Taxotere
ZD 1839
gefitinib
NSABP
advanced breast cancer
AstraZeneca

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Docetaxel
Gefitinib
Antimitotic Agents
Antineoplastic Agents
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 25, 2014