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

Sponsor:	Dartmouth-Hitchcock Medical Center
Collaborators:	National Cancer Institute (NCI) Norris Cotton Cancer Center
Information provided by:	Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:	NCT00080743

Purpose

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	Intervention	Phase
Breast Cancer	Drug: gefitinib Drug: tamoxifen citrate Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	ZD1839 (IRESSA) In Tamoxifen-Resistant Metastatic Breast Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Tamoxifen Tamoxifen citrate ZD1839

U.S. FDA Resources

Further study details as provided by Dartmouth-Hitchcock Medical Center:

Primary Outcome Measures:

Clinical benefit rate (complete response, partial response, and stable disease) for 26 weeks [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]

Enrollment:	2
Study Start Date:	January 2004
Study Completion Date:	November 2005
Primary Completion Date:	April 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Tamoxifen: Active Comparator Tamoxifen 20 mg po once daily	Drug: gefitinib 250 mg po once daily Drug: tamoxifen citrate 20 mg po once daily
Placebo: Placebo Comparator Placebo comparator one tablet po once daily	Drug: gefitinib 250 mg po once daily Drug: Placebo One pill po once daily

Detailed Description:

OBJECTIVES:

Primary

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

Secondary

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.

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
- 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

PATIENT CHARACTERISTICS:

Age

18 and over

Sex

Not specified

Menopausal status

Not specified

Performance status

ECOG 0-2

Life expectancy

At least 6 months

Hematopoietic

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

Hepatic

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

Renal

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

Pulmonary

No clinically active interstitial lung disease
- Patients with asymptomatic chronic stable radiographic changes are eligible

Other

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

PRIOR CONCURRENT THERAPY:

Biologic therapy

No concurrent trastuzumab (Herceptin®)

Chemotherapy

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

Radiotherapy

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

Surgery

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

Other

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00080743

Locations

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

Investigators

Principal Investigator:

Gary N. Schwartz, MD

Norris Cotton Cancer Center

More Information

Additional Information:

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

No publications provided

Responsible Party:	Dartmouth-Hitchcock Medical Center ( Gary N. Schwartz )
Study ID Numbers:	CDR0000355145, DMS-0236, ZENECA-IRUSIRES0162
Study First Received:	April 7, 2004
Last Updated:	August 4, 2009
ClinicalTrials.gov Identifier:	NCT00080743 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Dartmouth-Hitchcock Medical Center:

recurrent breast cancer
stage IV breast cancer

Additional relevant MeSH terms:

Estrogen Antagonists
Molecular Mechanisms of Pharmacological Action
Skin Diseases
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Hormone Antagonists
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Breast Neoplasms
Enzyme Inhibitors
Bone Density Conservation Agents

Selective Estrogen Receptor Modulators
Protein Kinase Inhibitors
Tamoxifen
Pharmacologic Actions
Estrogen Receptor Modulators
Neoplasms
Neoplasms by Site
Therapeutic Uses
Gefitinib
Breast Diseases

ClinicalTrials.gov processed this record on November 05, 2009