Bevacizumab in Treating Patients With Recurrent Sex Cord-Stromal Tumors of the Ovary
Bevacizumab in Treating Patients With Recurrent Sex Cord-Stromal Tumors of the Ovary
This phase II trial studies how well bevacizumab works in treating patients with sex
 cord-stromal tumors of the ovary that have come back. Monoclonal antibodies, such as
 bevacizumab, may block tumor growth in different ways by targeting certain cells. Bevacizumab
 may also stop the growth of tumor cells by blocking blood flow to the tumor.
PRIMARY OBJECTIVES:

 I. To estimate the anti-tumor activity of bevacizumab by assessing frequency of objective
 response in patients with recurrent sex cord-stromal tumors of the ovary who have measurable
 disease.

 SECONDARY OBJECTIVES:

 I. To determine the nature and degree of toxicity in these patients. II. To determine the
 overall survival and progression-free survival of these patients.

 TERTIARY OBJECTIVES:

 I. To quantify expression of angiogenic or lymphangiogenic markers in recurrent stromal
 tumors of the ovary to determine the frequency of alterations and potential utility of
 biologic agents directed at these proteins for inclusion in future studies.

 OUTLINE:

 Patients receive bevacizumab intravenously (IV) over 30-90 minutes on day 1. Courses repeat
 every 21 days in the absence of disease progression or unacceptable toxicity.

 After completion of study treatment, patients are followed every 3 months for 2 years, every
 6 months for 3 years, and then periodically thereafter.
Inclusion Criteria:

 -  Patients diagnosed with histologically confirmed recurrent ovarian stromal tumor
 (granulosa cell tumor, granulosa cell-theca cell tumor, Sertoli-Leydig cell tumor
 [androblastoma], steroid [lipid] cell tumor, gynandroblastoma, unclassified sex
 cord-stromal tumor, sex cord tumor with annular tubules)

 -  Patients must have measurable disease by Response Evaluation Criteria In Solid Tumors
 (RECIST) criteria

 -  Measurable disease is defined as at least one lesion that can be accurately
 measured in at least one dimension (longest dimension to be recorded); each
 ?target? lesion must be >= 20 mm when measured by conventional techniques,
 including palpation, plain x-ray, computed tomography (CT), and magnetic
 resonance imaging (MRI), or >= 10 mm when measured by spiral CT

 -  Patients must have a Gynecologic Oncology Group (GOG) performance grade of 0, 1, or 2

 -  Patients of childbearing potential must have a negative pregnancy test and must agree
 to practice an effective means of birth control

 -  Patients who have met the pre-entry requirements specified

 -  There are no restrictions on prior therapy; however, patients cannot have previously
 had treatment with bevacizumab

 -  Absolute neutrophil count (ANC) >= 1,000/?l

 -  Platelets greater than or equal to 75,000/?l

 -  Creatinine =< 1.5 x institutional upper limit normal (ULN)

 -  Bilirubin =< 1.5 x ULN

 -  Serum glutamic oxaloacetic transaminase (SGOT) less 2.5 x ULN

 -  Alkaline phosphatase less 2.5 x ULN

 -  Neuropathy (sensory and motor) less than or equal to Common Terminology Criteria for
 Adverse Events (CTCAE) version (v)3.0 grade 1

 -  Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 (or an
 in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic
 warfarin) and a partial thromboplastin time (PTT) < 1.2 times the upper limit of
 normal

 -  Patients must have signed an approved informed consent and authorization permitting
 release of personal health information

 Exclusion Criteria:

 -  Patients with newly diagnosed disease

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

 -  Patients who have received prior therapy with bevacizumab or other inhibitors of
 vascular endothelial growth factor (VEGF)

 -  Patients with active bleeding or pathologic conditions that carry high risk of
 bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major
 vessels

 -  Patients with history or evidence upon physical examination of central nervous system
 (CNS) disease, including primary brain tumor, seizures not controlled with standard
 medical therapy, any brain metastases, or history of cerebrovascular accident (CVA,
 stroke), transient ischemic attack (TIA), or subarachnoid hemorrhage within 6 months
 of the first date of treatment on this study

 -  Patients with clinically significant cardiovascular disease; this includes:

 -  Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm
 Hg

 -  Myocardial infarction or unstable angina within 6 months prior to registration

 -  New York Heart Association (NYHA) grade II or greater congestive heart failure

 -  Serious cardiac arrhythmic requiring medication.

 -  Grade 2 or greater peripheral vascular disease

 -  Patients with GOG performance grade of 3 or 4

 -  Patients with clinically significant peripheral arterial disease; e.g., claudication
 within 6 months

 -  Patients with known hypersensitivity to Chinese hamster ovary cell products or other
 recombinant human or humanized antibodies

 -  Patients with clinically significant proteinuria; urine protein should be screened by
 urine protein-creatinine ratio (UPCR); the UPCR has been found to correlate directly
 with the amount of protein excreted in a 24 hour urine collection; specifically; a
 UPCR of 1.0 is equivalent to 1.0 gram of protein in a 24 hour urine collection; obtain
 at least 4 ml of a random urine sample in a sterile container (does not have to be a
 24 hour urine); send sample to lab with request for urine protein and creatinine
 levels (separate requests); the lab will measure protein concentration (mg/dL) and
 creatinine concentration (mg/dL); the UPCR is derived as follows: protein
 concentration (mg/dL)/creatinine (mg/dL); patients must have a UPCR < 1.0 to allow
 participation in the study

 -  Patients with a history of cardiovascular accident (CVA) within 6 months prior to
 registration

 -  Patients with any signs of bowel obstruction or patients who require parenteral
 hydration and/or nutrition

 -  Patients whose circumstances do not permit completion of the study or the required
 follow-up

 -  Patients who are pregnant or nursing; patients who may become pregnant must agree to
 use contraceptive measures during the study and for at least 3 months after the
 completion of bevacizumab therapy

 -  Patients who have a major surgical procedure, open biopsy, or significant traumatic
 injury within 28 days prior to the first date of treatment on this study, or
 anticipate the need for major surgical procedure during the course of the study;
 patients with placement of vascular access device or core biopsy within 7 days prior
 to the first date of treatment on this study

 -  Patients with active infection requiring parenteral antibiotics

 -  Patients with a history of other invasive malignancies, with the exception of
 non-melanoma skin cancer, are excluded if there is any evidence of other malignancy
 being present within the last five years; patients are also excluded if their previous
 cancer treatment contraindicates this protocol therapy