Lapatinib in Treating Patients With Recurrent or Persistent Endometrial Cancer

PRIMARY OBJECTIVES:

I. Determine the 6-month progression-free survival of patients with recurrent or persistent
endometrial carcinoma treated with lapatinib.

II. Determine the nature and degree of toxicity of this drug in these patients.

SECONDARY OBJECTIVES:

I. Determine the objective response rate in patients treated with this drug. II. Determine
the duration of progression-free survival and overall survival in patients treated with this
drug.

III. Determine the effects of prognostic factors, such as initial performance status and
tumor grade, in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral lapatinib 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 and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 22-82 patients will be accrued for this study within 30-67
months.

Inclusion Criteria:

- Histologically confirmed endometrial carcinoma

- Recurrent or persistent disease

- Histologic confirmation of the original primary tumor is required

- Refractory to curative therapy or standard treatments

- Measurable disease

- At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques,
including palpation, plain x-ray, CT scan, or MRI OR ≥ 10 mm by spiral CT scan

- Must have at least 1 target lesion

- Tumors within a previously irradiated field are considered non-target
lesions

- Disease in an irradiated field as the only site of measurable disease
is considered a target lesion provided there has been clear progression
of the lesion since the completion of prior radiotherapy

- Must have received 1 prior chemotherapy regimen for endometrial carcinoma

- Initial therapy may have included high-dose therapy, consolidation, or extended
therapy administered after surgical or non-surgical assessment

- No more than 1 additional prior cytotoxic regimen for recurrent or persistent
disease

- Tumor accessible to guided core needle or fine needle biopsy

- Ineligible for a higher priority GOG protocol (e.g., any active GOG phase III protocol
for the same patient population)

- Performance status - GOG 0-2 (for patients who have received 1 prior treatment
regimen)

- Performance status - GOG 0-1 (for patients who have received 2 prior treatment
regimens)

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

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

- SGOT ≤ 2.5 times ULN

- Alkaline phosphatase ≤ 2.5 times ULN

- Creatinine ≤ 1.5 times ULN

- Cardiac ejection fraction normal by echocardiogram or MUGA

- No gastrointestinal (GI) tract disease resulting in an inability to take oral
medication

- No malabsorption syndrome

- No requirement for IV alimentation

- No uncontrolled inflammatory GI disease (e.g., Crohn's or ulcerative colitis)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No active infection requiring antibiotics

- No sensory or motor neuropathy > grade 1

- No history of allergic reaction attributed to compounds of similar chemical or
biological composition to lapatinib

- No other invasive malignancy within the past 5 years except nonmelanoma skin cancer

- At least 4 weeks since prior immunologic agents for the malignant tumor

- No prior trastuzumab (Herceptin^®) or any target-specific therapy directed to the HER
family (e.g., gefitinib, erlotinib, or cetuximab)

- At least 6 weeks since prior nitrosoureas or mitomycin for the malignant tumor and
recovered

- No prior non-cytotoxic chemotherapy for recurrent or persistent disease

- At least 1 week since prior hormonal therapy for the malignant tumor

- Concurrent hormone replacement therapy allowed

- Recovered from prior radiotherapy

- Recovered from prior surgery

- No prior surgery affecting absorption

- At least 4 weeks since other prior therapy for the malignant tumor

- No prior lapatinib

- No prior anticancer treatment that would preclude study treatment

- Concurrent oral anticoagulants (e.g., warfarin) allowed provided there is increased
monitoring of INR

- No concurrent CYP3A4 inducers or inhibitors

- No concurrent combination antiretroviral therapy for HIV-positive patients