Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI, Pharmaceutical / Industry	DMS-0236 ZENECA-IRUSIRES0162, NCT00080743

Special Category: NCI Avon award trial

Objectives

Primary

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

Secondary

1. Determine the toxic effects of these regimens in these patients.
2. 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.
3. Determine the pharmacokinetics of these regimens in these patients.

Entry 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

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

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/mm³
• Platelet count ≥ 100,000/mm³

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

Expected Enrollment

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

Outcomes

Clinical benefit rate (complete response, partial response, and stable disease) for 26 weeks

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.

Trial Contact Information

Trial Lead Organizations

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Gary Schwartz, MD, Principal investigator		Ph: 603-653-6181; 800-639-6918 Email: gary.n.schwartz@hitchcock.org

Registry Information
Official Title		ZD1839 (IRESSA®) In Tamoxifen-Resistant Metastatic Breast Cancer
Trial Start Date		2004-01-30
Registered in ClinicalTrials.gov		NCT00080743
Date Submitted to PDQ		2004-01-28
Information Last Verified		2005-12-07
NCI Grant/Contract Number		P30-CA23108

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