A Phase II Evaluation of Cediranib (Recentin; AZD2171, IND# 72740, NSC# 732208) in the Treatment of Recurrent or Persistent Endometrial Carcinoma

Inclusion Criteria:

- Histologically confirmed primary endometrial carcinoma including any of the following
epithelial 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

- Recurrent or persistent disease

- Refractory to curative therapy or established treatments

- Measurable disease defined as >= 1 lesion that can be accurately measured in >= 1
dimension (longest diameter to be recorded)

- Lesion must be >= 10 mm by CT scan, MRI, or caliper measurement by clinical exam
OR >= 20 mm by chest x-ray

- Lymph nodes must be > 15 mm in short axis by CT scan or MRI

- Patient must have >= 1 "target lesion" to assess response as defined by RECIST v. 1.1

- Tumors within a previous irradiated field are designated as non-target lesions
unless progression is documented OR a biopsy is obtained to confirm persistence
of disease >= 90 days after completion of radiotherapy

- Patient must not be eligible for a higher priority GOG protocol, if one exists

- Must have had 1 prior chemotherapeutic regimen for management of endometrial cancer
that may include 1 of the following:

- Chemotherapy

- Chemotherapy and radiotherapy

- Chemotherapy in conjunction with primary radiotherapy as a radio-sensitizer
will be counted as a systemic chemotherapy regimen

- Consolidation and/or maintenance therapy

- No CNS disease, including primary brain tumor or brain metastases

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

- ANC >= 1,500/mm^3

- Platelet count >= 100,000/mm^3

- Creatinine =< 1.5 times upper limit of normal (ULN) OR creatinine clearance >= 60
mL/min

- Urine protein: creatinine (UPC) ratio < 1.0 g

- Bilirubin =< 1.5 times ULN

- AST =< 2.5 times ULN

- Alkaline phosphatase =< 2.5 times ULN

- INR =< 1.5 times ULN (between 2 and 3 for patients on stable dose of therapeutic
warfarin)

- PTT =< 1.5 times ULN

- Amylase and lipase normal

- Thyroid stimulation hormone (TSH) and free thyroxine (Free T4) normal

- Peripheral neuropathy (sensory and motor) =< grade 1

- Negative pregnancy test

- Not pregnant or nursing

- Fertile patients must use effective contraception

- No active infection requiring antibiotics

- Uncomplicated urinary tract infection allowed

- No invasive malignancies within the past 3 years except nonmelanoma skin cancer or
curatively treated localized cancer of the breast, head and neck, or skin

- No serious non-healing wound, ulcer, or bone fracture, including the following:

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within the past 28 days

- No active bleeding or pathological conditions that carry high-risk of bleeding,
including the following:

- Known bleeding disorder

- Coagulopathy disorder

- Tumor involving major vessels

- No uncontrolled seizures with standard medical therapy

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

- Uncontrolled hypertension (defined as systolic blood pressure (BP) > 150 mm Hg
or diastolic BP > 100 mm Hg despite optimized antihypertensive therapy)

- Myocardial infarction or unstable angina within the past 6 months

- New York Heart Association (NYHA) grade II-IV congestive heart failure or
serious cardiac arrhythmia requiring medication

- Patients who received prior anthracycline treatment, including doxorubicin
hydrochloride and/or liposomal doxorubicin, and have an ejection fraction <
normal are not eligible for this study

- Peripheral vascular disease >= grade 2 as assessed by NCI CTCAE

- History of cerebrovascular accident (CVA, stroke), transient ischemic attack, or
subarachnoid hemorrhage within the past 6 months

- Mean QTc > 500 msec or history of familial long QT syndrome

- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human or humanized antibodies

- No concurrent amifostine or other protective reagents

- Recovered from recent surgery, radiotherapy, or chemotherapy

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

- At least 3 weeks since any other prior anticancer therapy

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

- Cytotoxic regimens include any agent that targets the genetic and/or mitotic
apparatus of dividing cells, resulting in dose-limiting toxicity to the bone
marrow and/or gastrointestinal mucosa

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

- Prior hormonal therapy allowed

- No prior cediranib maleate or other VEGF pathway-targeted therapy

- No prior cancer treatment that contraindicates this protocol therapy

- No prior radiotherapy to any portion of the abdominal cavity or pelvis within the
past 3 years other than treatment for endometrial cancer

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

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

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

- No major surgical procedure, open biopsy, or significant traumatic injury within the
past 28 days

- No anticipation of major surgical procedure during the course of the study

- No minor surgical procedures, fine needle aspirates, or core biopsies within the past
7 days