Selumetinib in Treating Patients With Recurrent or Persistent Endometrial Cancer

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