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Gefitinib With or Without Tamoxifen in Treating Patients With Tamoxifen-Resistant Metastatic Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00080743
Recruitment Status : Completed
First Posted : April 8, 2004
Last Update Posted : August 6, 2009
National Cancer Institute (NCI)
Norris Cotton Cancer Center
Information provided by:
Dartmouth-Hitchcock Medical Center

Brief Summary:

RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Hormone therapy using tamoxifen may fight breast cancer by blocking the use of estrogen by the tumor cells. Combining gefitinib with tamoxifen may be effective in killing tumor cells that have become resistant (stopped responding) to tamoxifen.

PURPOSE: This randomized phase II trial is studying how well giving gefitinib together with tamoxifen works compared to gefitinib alone in treating patients with metastatic breast cancer that has stopped responding to tamoxifen.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: gefitinib Drug: tamoxifen citrate Drug: Placebo Phase 2

Detailed Description:



  • Compare the rate of clinical benefit in patients with tamoxifen-resistant breast cancer treated with gefitinib with or without tamoxifen.


  • Determine the toxic effects of these regimens in these patients.
  • Determine whether changes in fludeoxyglucose F 18 uptake by positron emission tomography scan and changes in plasma DNA levels are indicators of an early response to gefitinib in these patients.
  • Determine the pharmacokinetics of these regimens in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to population (intent-to-treat population comprising all patients who receive 1 dose of treatment vs a subset of the intent-to-treat population, excluding patients with nonmeasurable/evaluable only disease). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral tamoxifen once daily. Beginning 14 days after the start of tamoxifen, patients receive oral gefitinib once daily.
  • Arm II: Patients receive oral placebo once daily. Beginning 14 days after the start of placebo, patients receive oral gefitinib as in arm I.

In both arms, treatment continues for 26 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed for 6 months.

PROJECTED ACCRUAL: A total of 46 patients (23 per treatment arm) will be accrued for this study within 23 months.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: ZD1839 (IRESSA) In Tamoxifen-Resistant Metastatic Breast Cancer
Study Start Date : January 2004
Actual Primary Completion Date : April 2005
Actual Study Completion Date : November 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Active Comparator: Tamoxifen
Tamoxifen 20 mg po once daily
Drug: gefitinib
250 mg po once daily
Other Name: ZD1839, Iressa

Drug: tamoxifen citrate
20 mg po once daily
Other Name: Nolvadex

Placebo Comparator: Placebo
Placebo comparator one tablet po once daily
Drug: gefitinib
250 mg po once daily
Other Name: ZD1839, Iressa

Drug: Placebo
One pill po once daily
Other Name: Sugar pill

Primary Outcome Measures :
  1. Clinical benefit rate (complete response, partial response, and stable disease) for 26 weeks [ Time Frame: 26 weeks ]

Information from the National Library of Medicine

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


  • Histologically confirmed breast cancer

    • Metastatic disease
  • Initial clinical benefit from tamoxifen for metastatic disease, defined by 1 of the following:

    • Stable disease for 24 weeks or longer
    • Objective tumor response
  • Documentation of clinical progression on tamoxifen within the past 6 weeks
  • Hormone receptor status:

    • Estrogen or progesterone receptor positive on most recently analyzed biopsy



  • 18 and over


  • Not specified

Menopausal status

  • Not specified

Performance status

  • ECOG 0-2

Life expectancy

  • At least 6 months


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


  • AST ≤ 1.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 times ULN


  • Creatinine ≤ 1.5 times ULN OR
  • Creatinine clearance ≥ 50 mL/min


  • No clinically active interstitial lung disease

    • Patients with asymptomatic chronic stable radiographic changes are eligible


  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No known hypersensitivity to gefitinib
  • No other malignancy within the past 5 years except basal cell carcinoma or carcinoma in situ of the cervix


Biologic therapy

  • No concurrent trastuzumab (Herceptin®)


  • No concurrent cytotoxic chemotherapy

Endocrine therapy

  • See Disease Characteristics
  • At least 2 weeks since other prior tamoxifen
  • No concurrent hormone replacement therapy
  • No other concurrent antiestrogens, including raloxifene
  • No concurrent aromatase inhibitors
  • No concurrent megestrol
  • Concurrent systemic steroids for reasons other than skin toxicity allowed provided the steroids were initiated before study entry AND dose remains stable


  • Concurrent palliative radiotherapy as short-term treatment for symptomatic bone metastases allowed provided other evaluable sites of disease are present AND treatment lasts no more than 14 days


  • Recovered from prior oncologic or other major surgery
  • No concurrent surgery during and for 7 days after study treatment
  • No concurrent ophthalmic surgery


  • Recovered from all prior therapy (except alopecia)
  • More than 30 days since prior investigational drugs
  • No other concurrent investigational agents
  • No concurrent administration of any of the following:

    • Phenytoin
    • Carbamazepine
    • Barbiturates
    • Rifampin
    • Phenobarbital
    • Hypericum perforatum (St. John's wort)
    • Systemic retinoids
    • CYP3A4 inhibitors (e.g., itraconazole)
    • Drugs that cause significant sustained elevation in gastric pH ≥ 5

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00080743

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United States, New Hampshire
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
National Cancer Institute (NCI)
Norris Cotton Cancer Center
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Principal Investigator: Gary N. Schwartz, MD Norris Cotton Cancer Center

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Responsible Party: Gary N. Schwartz, Dartmouth-Hitchcock Medical Center Identifier: NCT00080743     History of Changes
Other Study ID Numbers: CDR0000355145
First Posted: April 8, 2004    Key Record Dates
Last Update Posted: August 6, 2009
Last Verified: August 2009
Keywords provided by Dartmouth-Hitchcock Medical Center:
recurrent breast cancer
stage IV breast cancer
Additional relevant MeSH terms:
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Estrogen Antagonists
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Bone Density Conservation Agents
Protein Kinase Inhibitors
Enzyme Inhibitors