Bevacizumab in Treating Patients With Recurrent Sex Cord-Stromal Tumors of the Ovary

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase II Trial of NCI-Supplied Agent: Bevacizumab (rhuMAB VEGF) (NSC# 704865) for Recurrent Sex Cord-Stromal Tumors of the Ovary

Conditions
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Malignant Ovarian Epithelial Tumor, Ovarian Granulosa Cell Tumor, Ovarian Gynandroblastoma, Ovarian Sertoli-Leydig Cell Tumor, Ovarian Sex Cord Tumor With Annular Tubules, Ovarian Sex Cord-Stromal Tumor, Ovarian Sex Cord-Stromal Tumor of Mixed or Unclassified Cell Types, Ovarian Steroid Cell Tumor

Intervention / Treatment
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* Biological: Bevacizumab
* Other: Laboratory Biomarker Analysis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (bevacizumab)<br>Patients receive bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. | Biological: Bevacizumab<br>* Given IV<br>* Other names: rhuMab-VEGF;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response | Complete and Partial Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 | Every other cycle for 6 months; then every 3 months for two years; then every six months for three years; and at any other time if clinically indicated based on symptoms, physical signs suggestive of progressive disease or rising serum tumor maker levels | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression-Free Survival is the period from study entry until disease progression, death or date of last contact. | Every other cycle for 6 months; then every 3 months for two years; then every six months for three years; and at any other time if clinically indicated based on symptoms, physical signs suggestive of progressive disease or rising serum tumor maker levels | 
| Overall Survival | The observed length of life from entry into the study to death or the date of last contact. | From study entry to death or last contact, up to 5 years. | 
| Number of Participants With Episodes and Grade of Adverse Events as Assessed by Common Terminology for Adverse Events Version 3.0 | Adverse Events at least possibly related to study agent. | Up to 5 years |