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

NCT ID: NCT00080743

Last Updated: 2009-08-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-01-31
• Study Completion Date: 2005-11-30

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.

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Tamoxifen

Tamoxifen 20 mg po once daily

Group Type: ACTIVE_COMPARATOR

gefitinib

Intervention Type: DRUG

250 mg po once daily

tamoxifen citrate

Intervention Type: DRUG

20 mg po once daily

Placebo

Placebo comparator one tablet po once daily

Group Type: PLACEBO_COMPARATOR

gefitinib

Intervention Type: DRUG

250 mg po once daily

Placebo

Intervention Type: DRUG

One pill po once daily

Interventions

gefitinib

250 mg po once daily

Intervention Type: DRUG

tamoxifen citrate

20 mg po once daily

Intervention Type: DRUG

Placebo

One pill po once daily

Intervention Type: DRUG

Other Intervention Names

ZD1839, Iressa; Nolvadex; Sugar pill

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Norris Cotton Cancer Center

OTHER

Sponsor Role: collaborator

Dartmouth-Hitchcock Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Dartmouth-Hitchcock Medical Center

Principal Investigators

Gary N. Schwartz, MD

Role: PRINCIPAL_INVESTIGATOR

Norris Cotton Cancer Center

Locations

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Countries

United States

Other Identifiers

DMS-0236

Identifier Type: -

Identifier Source: secondary_id

ZENECA-IRUSIRES0162

Identifier Type: -

Identifier Source: secondary_id

CDR0000355145

Identifier Type: -

Identifier Source: org_study_id