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

Phase 2

Completed

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

Interventions: Biological: Bevacizumab
Other: Laboratory Biomarker Analysis

Registration Number: NCT00748657

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 36

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (bevacizumab)	Bevacizumab	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.
Treatment (bevacizumab)	Laboratory Biomarker Analysis	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.

Primary Outcome Measures

Name	Time	Method
Tumor Response	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	Complete and Partial Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival	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	Progression-Free Survival is the period from study entry until disease progression, death or date of last contact.
Overall Survival	From study entry to death or last contact, up to 5 years.	The observed length of life from entry into the study to death or the date of last contact.
Number of Participants With Episodes and Grade of Adverse Events as Assessed by Common Terminology for Adverse Events Version 3.0	Up to 5 years	Adverse Events at least possibly related to study agent.

Trial Locations

Locations (36): Los Angeles County-USC Medical Center
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Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
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Los Angeles, California, United States
University of Colorado Hospital
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Aurora, Colorado, United States
Hartford Hospital
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Hartford, Connecticut, United States
The Hospital of Central Connecticut
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New Britain, Connecticut, United States
Northeast Georgia Medical Center-Gainesville
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Gainesville, Georgia, United States
Northwestern University
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Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
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Chicago, Illinois, United States
Hinsdale Hematology Oncology Associates Incorporated
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Hinsdale, Illinois, United States
Sudarshan K Sharma MD Limted-Gynecologic Oncology
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Hinsdale, Illinois, United States
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Los Angeles County-USC Medical Center
🇺🇸Los Angeles, California, United States