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Gefitinib, Trastuzumab, and Docetaxel in Treating Patients With Metastatic Breast Cancer

This study has been completed.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center Identifier:
First received: July 8, 2004
Last updated: October 1, 2015
Last verified: October 2015

RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining gefitinib and trastuzumab with docetaxel may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the best dose of docetaxel when given together with gefitinib and trastuzumab in treating patients with metastatic breast cancer.

Condition Intervention Phase
Breast Cancer
Biological: trastuzumab
Drug: docetaxel
Drug: gefitinib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Trial of ZD1839 (Iressa®), Trastuzumab (Herceptin®), and Docetaxel (Taxotere®) in Patients With erbB-2 (HER-2) Overexpressing, Stage IV Breast Carcinoma

Resource links provided by NLM:

Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Time to progression at 6 months and 1 year [ Time Frame: 1 year ]
  • Feasibility at 6 months and 1 year [ Time Frame: 1 year ]

Secondary Outcome Measures:
  • Response rate by RECIST at 1 and 2 years [ Time Frame: 1 year ]
  • Overall survival at 1 and 2 years [ Time Frame: 2 years ]
  • Changes in molecular markers at 1 and 2 years [ Time Frame: 2 years ]

Enrollment: 31
Study Start Date: January 2004
Study Completion Date: August 2015
Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ZD1839, Trastuzumab and Docetaxel Biological: trastuzumab
Cycle 1 loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks for subsequent cycles.
Drug: docetaxel
75 mg/m2 every three weeks, or 60 mg/m2 every three weeks depending on study findings
Drug: gefitinib
250 mg daily or 250 mg daily on days 2 through 14 depending on study findings

Detailed Description:



  • Determine the safety and efficacy of gefitinib, trastuzumab (Herceptin®), and docetaxel, in terms of time to disease progression, in patients with HER2/neu-overexpressing metastatic adenocarcinoma of the breast.


  • Determine the objective tumor response rate in patients treated with this regimen.
  • Correlate expression and/or degree of phosphorylation of epidermal growth factor receptor, HER2/neu, c-fos, Akt, ERK½, P13K, p53, p21, and p27 with outcome in patients treated with this regimen.

OUTLINE: This is a phase I, multicenter, dose-escalation study of docetaxel followed by a phase II study. Patients are stratified according to trastuzumab (Herceptin®)-naive vs trastuzumab-failure.

  • Phase I: Patients receive oral gefitinib once daily on days 2-14. Patients also receive trastuzumab* IV over 30-90 minutes and docetaxel IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

NOTE: *Trastuzumab is given at a higher dose (loading dose) in course 1 and then at a lower dose in subsequent courses.

Cohorts of 3-6 patients receive docetaxel at dose level 1. If no dose-limiting toxicity (DLT) is observed in the first cohort of 3 patients, the dose of docetaxel remains the same. If 1 DLT is observed in the first cohort of 3 patients, 3 additional patients are added (for a total of 6 patients) to dose level 1. If no further DLTs are observed at dose level 1, the dose of docetaxel remains the same. If 2 of 3 or 2 of 6 patients experience DLT at dose level 1, the dose of docetaxel is considered above the maximum tolerated dose (MTD) and is subsequently reduced. If 2 of 3 or 2 of 6 patients experience DLT at the reduced dose of docetaxel, the study is stopped.

  • Phase II: Patients receive docetaxel at the MTD and gefitinib and trastuzumab as in phase I.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 3-76 patients will be accrued for this study within 26 months.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed adenocarcinoma of the breast

    • Metastatic disease
  • HER-2/neu overexpression (3+ by immunohistochemistry OR 2+ by fluorescence in situ hybridization)
  • Measurable or evaluable disease
  • Hormone receptor status:

    • Not specified



  • 18 and over


  • Male or female

Menopausal status

  • Not specified

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified


  • Absolute granulocyte count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3


  • AST and ALT < 2.5 times upper limit of normal (ULN) (5.0 times ULN in the presence of liver metastases)
  • Bilirubin < 1.5 times ULN
  • No unstable or uncompensated hepatic disease


  • Creatinine < 1.6 mg/dL
  • No unstable or uncompensated renal disease


  • LVEF > 45% by echocardiogram or MUGA
  • No prior New York Heart Association class I-IV heart disease
  • No prolonged PR interval or atrioventricular block on ECG
  • No unstable or uncompensated cardiac disease


  • No unstable or uncompensated respiratory disease
  • No clinically active interstitial lung disease

    • Patients who are asymptomatic and have chronic stable radiographic changes are allowed


  • No autoimmune disorders
  • No conditions of immunosuppression
  • No severe hypersensitivity to taxane or gefitinib or any of its excipients


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other prior or concurrent malignancy within the past 5 years except basal cell carcinoma or carcinoma in situ of the cervix
  • No other severe or uncontrolled systemic disease
  • No other acute or chronic medical condition that would preclude study participation
  • No other significant clinical disorder or laboratory finding that would preclude study participation
  • No psychiatric illness that would preclude study compliance


Biologic therapy

  • Prior adjuvant trastuzumab (Herceptin®) allowed if > 6 months elapsed before disease recurrence
  • No prior trastuzumab for metastatic breast cancer
  • No prior monoclonal antibodies directed at the epidermal growth factor receptor (EGFR)


  • Prior adjuvant chemotherapy (or as first-line therapy for metastatic breast cancer) allowed
  • Prior adjuvant taxane allowed if completed > 6 months before diagnosis of metastatic breast cancer
  • No prior docetaxel for metastatic breast cancer

Endocrine therapy

  • Prior adjuvant hormonal therapy (or as first-line therapy for metastatic breast cancer) allowed
  • No concurrent hormonal therapy

    • Concurrent steroids allowed provided dose is stable


  • Not specified


  • Fully recovered from prior oncologic or other major surgery
  • No concurrent surgery within 7 days of gefitinib administration


  • Recovered from prior anticancer therapy (alopecia allowed)
  • More than 30 days since prior non-approved drug or investigational agent
  • No other prior EGFR-directed therapy (i.e., tyrosine kinase inhibitors)
  • No concurrent use of any of the following medications:

    • Phenytoin
    • Carbamazepine
    • Barbiturates
    • Rifampin
    • Hypericum perforatum (St. John's wort)
  • No other concurrent anticancer therapy
  • No concurrent cardioprotective drugs
  • No concurrent oral retinoids
  • Concurrent participation in the City of Hope indium-labeled trastuzumab imaging study allowed
  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 identifier: NCT00086957

United States, California
Tower Cancer Research Foundation
Beverly Hills, California, United States, 90211-1850
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
Hematology Oncology Consultants-Hemet
Hemet, California, United States, 92543
Breastlink Medical Group, Incorporated at Long Beach Memorial Medical Center
Long Beach, California, United States, 90806
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90089-9181
City of Hope Medical Group
Pasadena, California, United States, 91105
Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
Principal Investigator: George Somlo, MD City of Hope Medical Center
  More Information

Somlo G, Koczywas M, Luu T, et al.: A phase I-II study of trastuzumab, gefitinib, and docetaxel as first line chemotherapy in patients with HER-2 overexpressing stage IV breast carcinoma. [Abstract] Breast Cancer Research and Treatment 94 (Suppl 1): A-2035, 2005.

Responsible Party: City of Hope Medical Center Identifier: NCT00086957     History of Changes
Other Study ID Numbers: 03049  P30CA033572  CHNMC-03049  ZENECA-1839US/0274  ZENECA-IRUSIRES0012  CDR0000371908 
Study First Received: July 8, 2004
Last Updated: October 1, 2015

Keywords provided by City of Hope Medical Center:
stage IV breast cancer
male breast cancer
recurrent breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors processed this record on February 17, 2017