Gemcitabine Hydrochloride and Docetaxel With or Without Bevacizumab in Treating Patients With Advanced or Recurrent Uterine Leiomyosarcoma

Inclusion Criteria:

• Patients must have advanced or recurrent uterine leiomyosarcoma with documenteddisease progression; histologic confirmation of the original primary tumor is required

• All patients must have measurable disease as defined by RECIST 1.1; measurable diseaseis defined 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 CT, MRI or caliper measurement by clinical exam; or >= 20 mm when measuredby chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI

• Patient must have at least one "target lesion" to be used to assess response on thisprotocol as defined by RECIST 1.1; tumors within a previously irradiated field will bedesignated as "non-target" lesions unless progression is documented or a biopsy isobtained to confirm persistence at least 90 days following completion of radiationtherapy

• Patients must have a GOG Performance Status of 0, 1, or 2

• Patients must have recovered from effects of recent surgery, radiotherapy or othertherapy

• Patients should be free of active infection requiring antibiotics (with the exceptionof an uncomplicated UTI)

• Any hormonal therapy directed at the malignant tumor must be discontinued at least oneweek prior to first day of study treatment; continuation of hormone replacementtherapy is permitted

• Platelet count greater than or equal to 100,000/mm^3

• ANC count greater than or equal to 1,500/mm^3

• Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN), per NCICTCAE Version 4.0 Grade 1

• Bilirubin within normal range (CTCAE Version 4 Grade 0)

• SGOT and alkaline phosphatase less than or equal to 2.5 x ULN, per the CTCAE Version 4.0 Grade 1)

• SGOT less than or equal to 2.5 x ULN, per the CTCAE Version 4.0 Grade 1

• Alkaline phosphatase less than or equal to 2.5 x ULN, per the CTCAE Version 4.0 Grade 1

• Neuropathy (sensory and motor) less than or equal to Grade 1 per the CTCAE Version 4.0.

• No history of transient ischemic attack (TIA) or stroke or CNS hemorrhage within thepast 6 months

• Urine protein creatinine (UPC) ratio must be < 1.0 gm; if UPC ratio >= 1, collectionof 24-hour urine measurement of urine protein is recommended

• PT such that international normalized ratio (INR) is =< 1.5 and a PTT =< 1.5 times theinstitutional upper limit of normal (or an in-therapeutic-range INR, usually between 2and 3, if a patient is on a stable dose of therapeutic warfarin)

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

• Patients must meet pre-entry requirements

• 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 received prior cytotoxic chemotherapy for management of uterinesarcoma; patients who have received prior VEGF-pathway targeted agent such asbevacizumab, PTK787, VEGF-trap, or who have received prior treatment with amulti-kinase inhibitor such as sorafenib or sunitinib are not eligible

• Patients who have had prior therapy with docetaxel or gemcitabine or bevacizumab

• Patients with a history of other invasive malignancies, with the exceptions ofnon-melanoma skin cancer, carcinoma in situ of the cervix, and ductal carcinoma insitu of the breast, are excluded if there is any evidence of other malignancy beingpresent within the last five years; patients are also excluded if their previouscancer treatment contraindicates this protocol therapy

• Patients with active bleeding or pathologic conditions that carry high risk ofbleeding, such as known bleeding disorder, coagulopathy, or tumor involving majorvessels; (necessary use of warfarin or low molecular weight heparin is permitted,provided the INR is maintained in the therapeutic range of approximately 2-3)

• Patients with major surgery or significant traumatic injury within 28 days prior tostudy entry

• Patients with a history of abdominal fistula or perforation within the past 12 months

• Patients with a current, serious, non-healing wound, ulcer, or bone fracture

• Patients with history or evidence upon physical examination of CNS disease, includinghistory of primary brain tumor, or any history of brain metastases, or seizures notcontrolled with standard medical therapy

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

• Cardiovascular function; specifically, patient may not have:

• Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 100 mmHg in a patient with no history of hypertension; patients with a history ofhypertension before enrollment on study are permitted, but such patients musthave BP less than or equal to 140/90 mmHg; use of blood pressure medications toachieve and maintain blood pressure control is permitted

• Myocardial infarction or unstable angina within 6 months of the first date ofbevacizumab/placebo 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 < 50% will be excluded from the study

• Grade 1, Category 2 or greater, peripheral vascular disease; patient cannot haveanything worse than mild, symptomatic claudication with exercise

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

• History of pulmonary embolism or deep vein thrombosis in the past 6 months

• Patients with, or with anticipation of, invasive procedures as defined below:

• Major surgical procedure, open biopsy or significant traumatic injury within 28days prior to the first date of bevacizumab/placebo therapy

• Major surgical procedure anticipated during the course of the study.

• Minor surgical procedures (i.e., mediport insertion), fine needle aspirates, orcore biopsies within 7 days prior to the first date of bevacizumab/placebotherapy

• Patients who are pregnant or nursing