RATIONALE: Biological therapies such as gefitinib may interfere with the growth of tumor cells and slow the growth of endometrial cancer.

PURPOSE: Phase II trial to study the effectiveness of gefitinib in treating patients who have persistent or recurrent endometrial cancer.

Condition	Treatment or Intervention	Phase
recurrent endometrial cancer	Drug: gefitinib  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the 6-month progression-free survival of patients with persistent or recurrent endometrial carcinoma after receiving gefitinib.
• Determine the nature and degree of toxicity of this drug in these patients.
• Determine the progression-free and overall survival of patients treated with this drug.
• Determine the effects of this drug on the levels of epidermal growth factor receptors (EGFR), c-ErbB2 (HER-2/neu) receptors, estrogen receptors (ER), and progesterone receptors (PR) (both PR and PRB) in tumor specimens of these patients.
• Determine if an association exists between the levels of EGFR, ER, PR, PRB, and HER-2/neu serum concentrations of gefitinib, gefitinib activity, and soluble EGFR and clinical outcome in patients treated with this drug.
• Determine the frequency of clinical response (partial and complete response) in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral gefitinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 22-60 patients will be accrued for this study within 2.5-6 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed primary endometrial carcinoma
• Recurrent or persistent disease
• Received 1 prior chemotherapy regimen for endometrial carcinoma
• Initial treatment may include high-dose, consolidation, or extended therapy administered after surgical or nonsurgical assessment
• At least 1 unidimensionally measurable lesion
• At least 20 mm by conventional techniques (including palpation, plain x-ray, CT scan, and MRI) OR
• At least 10 mm by spiral CT scan
• Must have at least 1 target lesion for response assessment
• Tumors within a previously irradiated field are designated as non-target lesions
• Disease in a previously irradiated field as the only site of measurable disease is allowed only if there has been clear progression of the lesion since the completion of radiotherapy
• Must have a tumor that is accessible for guided core needle or fine needle biopsy
• Ineligible for a higher priority GOG protocol, defined as any active phase III protocol for the same patient population, if one exists

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• GOG 0-2 (for patients who received 1 prior regimen)
• GOG 0-1 (for patients who received 2 prior regimens)

Life expectancy:

• Not specified

Hematopoietic:

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

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT no greater than 2.5 times ULN
• Alkaline phosphatase no greater than 2.5 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No unstable cardiac disease or myocardial infarction within the past 6 months
• History of coronary artery disease, congestive heart failure, or dysrhythmia allowed if on a stable regimen for at least 3 months

Other:

• No active infection requiring antibiotics
• No active corneal disease (e.g., keratoconjunctivitis)
• No grade 2 or greater sensory and motor neuropathy
• No other invasive malignancy within the past 5 years except nonmelanoma skin cancer
• No signs or symptoms of bowel dysfunction that would preclude successful ingestion of oral study medication
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• At least 3 weeks since prior immunologic agents directed at malignant tumor
• No concurrent anticancer immunotherapy

Chemotherapy:

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy directed at the malignant tumor and recovered
• No prior non-cytotoxic chemotherapy for recurrent or persistent disease
• No concurrent anticancer chemotherapy

Endocrine therapy:

• At least 1 week since prior hormonal therapy directed at malignant tumor
• No concurrent anticancer hormonal therapy

Radiotherapy:

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy directed at malignant tumor and recovered
• No concurrent anticancer radiotherapy

Surgery:

• At least 4 weeks since prior surgery except minor procedures using local anesthesia (e.g., placement of a central venous port) and recovered

Other:

• At least 3 weeks since any other prior therapy directed at malignant tumor
• One additional prior cytotoxic regimen for recurrent or persistent disease allowed
• No prior gefitinib or other epidermal growth factor receptor inhibitor
• No prior cancer treatment that would contraindicate study therapy
• No concurrent CYP 3A4 inducers (including phenytoin, carbamazepine, barbiturates, nafcillin, rifampin, or Hypericum perforatum [St. John's Wort])
• No other concurrent investigational or antineoplastic agents
• No concurrent chlorpromazine

Hawaii
      MBCCOP - Hawaii, Honolulu,  Hawaii,  96813,  United States
Maryland
      Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support, Bethesda,  Maryland,  20892-1182,  United States
New Mexico
      University of New Mexico Health Science Center, Albuquerque,  New Mexico,  87131-5286,  United States
North Carolina
      Lineberger Comprehensive Cancer Center, UNC, Chapel Hill,  North Carolina,  27599-7295,  United States
Pennsylvania
      Abington Memorial Hospital, Abington,  Pennsylvania,  19001-3788,  United States
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111,  United States
Texas
      University of Texas Medical Branch, Galveston,  Texas,  77555-0587,  United States
Norway
      Norwegian Radium Hospital, Oslo,  N-0310,  Norway

Study chairs or principal investigators

Kimberly Leslie, MD,  Study Chair,  University of New Mexico Health Science Center   

Study ID Numbers:  CDR0000069057; GOG-0229C
Record last reviewed:  December 2003
Last Updated:  October 13, 2004
Record first received:  December 7, 2001
ClinicalTrials.gov Identifier:  NCT00027690
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08