Inclusion Criteria:

- Histologically confirmed* endometrial epithelial carcinoma, including any of the
following cell types:

- Endometrioid adenocarcinoma

- Serous adenocarcinoma

- Undifferentiated carcinoma

- Clear cell adenocarcinoma

- Mixed epithelial carcinoma

- Adenocarcinoma not otherwise specified

- Mucinous adenocarcinoma

- Squamous cell carcinoma

- Transitional cell carcinoma

- Mesonephric carcinoma

- Recurrent or persistent disease that is refractory to curative therapy or established
treatments

- Measurable disease, defined as ≥ 1 lesion that can be measured in ≥ 1 dimension
(longest dimension to be recorded)

- Each lesion must be ≥ 20 mm when measured by conventional techniques (palpation,
plain x-ray, CT scan, or MRI) OR ≥ 10 mm when measured by spiral CT scan

- Must have ≥ 1 target lesion to be used to assess response, as defined by RECIST
criteria

- Tumors within a previously irradiated field are designated as "non-target"
lesions unless progression is documented or a biopsy is obtained to confirm
persistence ≥ 90 days following completion of radiotherapy

- Must have received 1 prior chemotherapeutic regimen for the management of endometrial
carcinoma

- Chemotherapy administered as a radiosensitizer in conjunction with primary
radiotherapy is considered a systemic chemotherapy regimen

- Not eligible for a higher priority GOG protocol, if one exists (e.g., any active
phase III GOG protocol for the same patient population)

- No prior or concurrent CNS disease (treated or untreated) by physical examination,
including primary brain tumor or brain metastases

- GOG performance status (PS) 0-2 (for patients who received 1 prior treatment regimen)

- GOG PS 0-1 (for patients who received 2 prior treatment regimens)

- ANC ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

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

- Bilirubin ≤ 1.5 times ULN

- SGOT ≤ 2.5 times ULN

- Alkaline phosphatase ≤ 2.5 times ULN

- PT/INR ≤ 1.5 OR in-range INR (between 2 and 3) if patient is on a stable dose of
therapeutic warfarin

- PTT ≤ 1.5 times ULN

- Oxygen saturation ≥ 88% on room air

- QTc < 450 msec by EKG

- LVEF normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 6 months after
completion of study therapy

- No neuropathy (sensory or motor) > grade 1

- No active infection requiring antibiotics

- Uncomplicated urinary tract infection allowed

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

- No serious, non-healing wound, ulcer, or bone fracture

- No history of abdominal fistula or gastrointestinal perforation

- No intra-abdominal abscess within the past 28 days

- No active bleeding or pathological condition that would carry a high risk of bleeding
(e.g., bleeding disorder, coagulopathy, or tumor involving major vessels)

- No seizures not controlled with standard medical therapy

- No clinically significant cardiovascular disease including, but not limited to, any
of the following:

- Uncontrolled hypertension, defined as systolic BP > 140 mm Hg or diastolic BP >
90 mm Hg

- Myocardial infarction or unstable angina within the past 6 months

- NYHA class II-IV congestive heart failure

- Serious cardiac arrhythmia requiring medication, including atrial fibrillation
requiring rate-controlling medication

- Peripheral vascular disease ≥ grade 2

- Cerebrovascular accident (i.e., CVA, stroke), transient ischemic attack, or
subarachnoidal hemorrhage within the past 6 months

- No evidence of serious ventricular arrhythmia (i.e., ventricular tachycardia or
ventricular fibrillation ≥ 3 beats in a row) by EKG

- Concurrent low molecular weight heparin for treatment of venous thromboembolic
disease allowed provided patient is considered clinically stable on this regimen

- Recovered from prior surgery, radiotherapy, or chemotherapy

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

- At least 3 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas
or mitomycin C)

- At least 3 weeks since other prior therapy directed at the malignant tumor, including
immunologic agents

- One prior cytotoxic regimen for the management of recurrent or persistent endometrial
disease allowed

- No prior non-cytotoxic chemotherapy for the management of endometrial cancer, except
hormonal therapy

- No prior anticancer therapy that contraindicates study therapy

- No prior MEK inhibitor AZD6244 or other specific MEK/ERK/MAPK pathway targeted
therapy

- No prior chemotherapy for any abdominal or pelvic tumor other than for the treatment
for endometrial cancer within the past 5 years

- Prior adjuvant chemotherapy for localized breast cancer allowed provided it was
completed > 3 years ago AND the patient remains free of recurrent or metastatic
disease

- No prior radiotherapy to any portion of the abdominal cavity or pelvis other than for
the treatment of endometrial cancer within the past 5 years

- Prior radiotherapy for localized cancer of the breast, head and neck, or skin is
allowed provided it was completed > 3 years ago AND the patient remains free of
recurrent or metastatic disease

- No concurrent medication that may prolong the QTc interval

- No other concurrent investigational therapy

- No concurrent combination antiretroviral therapy for HIV-positive patients