Erlotinib in Treating Patients With Locally Advanced and/or Metastatic Endometrial Cancer

A Phase II Study of OSI-774 (NSC 718781) in Patients With Locally Advanced and/or Metastatic Carcinoma of the Endometrium

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

PURPOSE: Phase II trial to determine the effectiveness of erlotinib in treating patients who have locally advanced and/or metastatic endometrial cancer.

OBJECTIVES:

• Determine the efficacy of erlotinib, in terms of response rate and duration of stable disease, in patients with locally advanced and/or metastatic carcinoma of the endometrium.
• Determine the toxicity of this drug in these patients.
• Determine the time to progression and duration of response in patients treated with this drug.
• Correlate objective tumor response with levels of epidermal growth factor receptor expression in patients treated with this drug.

OUTLINE: This is a multicenter study.

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

Patients are followed at 4 weeks. Patients with complete or partial response or stable disease are also followed every 3 months until relapse or death.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 12-18 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic and/or locally advanced adenocarcinoma or adenosquamous carcinoma of the endometrium

  • Incurable by standard therapies

• Clinically and/or radiologically documented disease with at least 1 unidimensionally measurable site

  • At least 20 mm by x-ray, physical exam, or CT scan OR
  • At least 10 mm by spiral CT scan
  • Bone metastases considered nonmeasurable

• Tumor tissue from primary tumor available for assessing epidermal growth factor receptor (EGFR) status

• No uterine sarcomas (leiomyosarcoma), mixed mullerian tumors, and/or adenosarcomas

• No known brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Platelet count at least 100,000/mm3
• Absolute granulocyte count at least 1,500/mm3

Hepatic:

• Bilirubin no greater than upper limit of normal (ULN)
• AST/ALT no greater than 2.5 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No symptomatic congestive heart failure
• No unstable angina
• No cardiac arrhythmia

Gastrointestinal:

• No gastrointestinal (GI) tract disease that would preclude ability to take oral medication
• No requirement for IV alimentation
• No uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)
• No active peptic ulcer disease

Ophthalmic:

• No significant ophthalmologic abnormalities, including any of the following:

  • Prior severe dry eye syndrome, Sjogren's syndrome, or keratoconjunctivitis sicca
  • Severe-exposure keratopathy
  • Disorders that would increase the risk of epithelium-related complications (e.g., bullous keratopathy, aniridia, severe chemical burns, or neutrophilic keratitis)
  • Congenital abnormality (e.g., Fuch's dystrophy)
  • Abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
  • Abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test)

• No concurrent ocular inflammation or infection

Other:

• No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix
• No prior allergic reaction attributed to compounds of similar biological or chemical composition to erlotinib
• No other concurrent serious illness or medical condition that would preclude study
• No prior significant neurologic or psychiatric disorder that would preclude study
• No active uncontrolled infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy for endometrial cancer

Endocrine therapy:

• No more than 1 prior hormonal therapy (progestational agent or aromatase inhibitor) in the adjuvant or metastatic setting
• At least 1 week since prior hormonal therapy

Radiotherapy:

• At least 4 weeks since prior radiotherapy (except for low-dose palliative radiotherapy) and recovered

Surgery:

• At least 3 weeks since prior major surgery and recovered
• No prior surgical procedures affecting absorption
• No concurrent ophthalmic surgery

Other:

• No prior EGFR-targeting therapies
• No other concurrent investigational therapy
• No other concurrent anticancer therapy
• Concurrent oral anticoagulants (e.g., warfarin) allowed provided there is increased vigilance with respect to monitoring INR
• Concurrent low molecular weight heparin allowed at investigator's discretion