Cediranib Maleate in Treating Patients With Recurrent or Persistent Endometrial Cancer

Inclusion Criteria:

• Patients must have recurrent or persistent endometrial carcinoma, which is refractoryto curative therapy or established treatments; histologic confirmation of the originalprimary tumor is required

• Patients with the following histologic epithelial cell types are eligible:endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma,clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma nototherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell carcinoma,and transitional cell carcinoma

• All patients must have measurable disease; measurable disease is defined by ResponseEvaluation Criteria in Solid Tumors (RECIST) (version 1.1); measurable disease isdefined as at least one lesion that can be accurately measured in at least onedimension (longest diameter to be recorded); each lesion must be >= 10 mm whenmeasured by computed tomography (CT), magnetic resonance imaging (MRI) or calipermeasurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodesmust be >= 15 mm in short axis when measured by CT or MRI

• Patients must have at least one "target lesion" to be used to assess response on thisprotocol as defined by RECIST version 1.1; tumors within a previously irradiated fieldwill be designated as "non-target" lesions unless progression is documented or abiopsy is obtained to confirm persistence at least 90 days following completion ofradiation therapy

• Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG)protocol, if one exists; in general, this would refer to any active GOG Phase IIIprotocol or Rare Tumor protocol for the same patient population

• Patients who have received one prior regimen must have a GOG performance status of 0, 1, or 2; patients who have received two prior regimens must have a GOG performancestatus of 0 or 1

• Recovery from effects of recent surgery, radiotherapy, or chemotherapy

• Patients should be free of active infection requiring antibiotics (with theexception of uncomplicated urinary tract infection [UTI])

• Any hormonal therapy directed at the malignant tumor must be discontinued atleast one week prior to registration

• Any other prior therapy directed at the malignant tumor must be discontinued atleast three weeks prior to registration

• Patients must have had one prior chemotherapeutic regimen for management ofendometrial carcinoma; initial treatment may include chemotherapy, chemotherapy andradiation therapy, and/or consolidation/maintenance therapy; chemotherapy administeredin conjunction with primary radiation as a radio-sensitizer WILL be counted as asystemic chemotherapy regimen

• Patients are allowed to receive, but are not required to receive, one additionalcytotoxic regimen for management of recurrent or persistent disease according to thefollowing definition: cytotoxic regimens include any agent that targets the geneticand/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to thebone marrow and/or gastrointestinal mucosa

• Note: Patients on this non-cytotoxic study are allowed to receive one additionalcytotoxic chemotherapy regimen for management of recurrent or persistent disease,as defined above; however, due to the novel nature of biologic compounds,patients are encouraged to enroll on second-line non-cytotoxic studies prior toreceiving additional cytotoxic therapy

• Patients must have NOT received any non-cytotoxic chemotherapy for management ofrecurrent or persistent disease; prior hormonal therapy is allowed

• Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl

• Platelets greater than or equal to 100,000/mcl

• Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN) orcreatinine (Cr) clearance >= 60 ml/min

• Bilirubin less than or equal to 1.5 x upper limit of normal (ULN)

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) lessthan or equal to 2.5 x ULN

• Alkaline phosphatase less than or equal to 2.5 x ULN

• Neuropathy (sensory and motor) less than or equal to grade 1

• Urine protein creatinine (UPC) ratio must be < 1.0 gm

• If UPC ratio >= 1, collection of 24-hour urine measurement of urine protein isrecommended

• Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 x ULN (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose oftherapeutic warfarin) and a partial thromboplastin time (PTT) =< 1.5 x ULN

• Patients must have an amylase and lipase =< ULN

• Patients must have a thyroid stimulating hormone (TSH) level and a free thyroxine (free T4) level within the institutional normal limits

• Patients must have signed an approved informed consent and authorization permittingrelease of personal health information

• Patients must meet pre-entry requirements as specified

• Patients of childbearing potential must have a negative serum pregnancy test prior tothe study entry and be practicing an effective form of contraception

Exclusion Criteria:

• Patients who have had prior therapy with cediranib (AZD 2171) or other VEGFpathway-targeted therapy

• Patient with a history of other invasive malignancies, with the exception ofnon-melanoma skin cancer and other specific malignancies as noted, are excluded ifthere is any evidence of other malignancy being present within the last three years;patients are also excluded if their previous cancer treatment contraindicates thisprotocol therapy

• Patients who have received prior radiotherapy to any portion of the abdominal cavityor pelvis OTHER THAN for the treatment of endometrial cancer within the last threeyears are excluded; prior radiation for localized cancer of the breast, head and neck,or skin is permitted, provided that it was completed more than three years prior toregistration, and the patient remains free of recurrent or metastatic disease

• Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHERTHAN for the treatment of endometrial cancer within the last three years are excluded;patients may have received prior adjuvant chemotherapy for localized breast cancer,provided that it was completed more than three years prior to registration, and thatthe patient remains free of recurrent or metastatic disease

• Patients with serious, non-healing wound, ulcer, or bone fracture; this includeshistory of abdominal fistula, gastrointestinal perforation or intra-abdominal abscesswithin 28 days prior to the first date of cediranib (AZD 2171) therapy

• Patients with active bleeding or pathologic conditions that carry high risk ofbleeding, such as known bleeding disorder, coagulopathy, or tumor involving majorvessels

• Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standardmedical therapy or any brain metastases

• Patients with clinically significant cardiovascular disease; this includes:

• Uncontrolled hypertension defined as systolic > 150 mmHg or diastolic > 100 mmHgdespite optimized antihypertensive therapy

• Myocardial infarction or unstable angina within 6 months of the first date ofcediranib (AZD 2171) therapy

• New York Heart Association (NYHA) grade II or greater congestive heart failure orserious cardiac arrhythmia requiring medication; women who have received priortreatment with an anthracycline (including doxorubicin and/or liposomaldoxorubicin) and have an ejection fraction < institutional lower limit of normal (LLN) will be excluded from the study

• CTCAE grade 2 or greater peripheral vascular disease

• History of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of cediranib (AZD 2171) therapy

• Mean corrected QT interval (QTc) > 500 msec or history of familial long QTsyndrome

• Patients with known hypersensitivity to Chinese hamster ovary cell products or otherrecombinant human or humanized antibodies

• Patients undergoing invasive procedures as defined below:

• Major surgical procedure, open biopsy or significant traumatic injury within 28days prior to the first date of cediranib (AZD 2171) therapy

• Major surgical procedure anticipated during the course of the study

• Minor surgical procedures, fine needle aspirates, or core biopsies within 7 daysprior to the first date of cediranib (AZD2171) therapy

• Patients who are pregnant or nursing