Clinical trial NCT00748657: Bevacizumab in Treating Patients With Recurrent Sex Cord-Stromal Tumors of the Ovary
Official title: A Phase II Trial of NCI-Supplied Agent: Bevacizumab (rhuMAB VEGF) (NSC# 704865) for Recurrent Sex Cord-Stromal Tumors of the Ovary
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: NRG Oncology
First posted: 2008-09-08
Enrollment: 36
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Tumor Response
timeFrame: 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 outcomes:
measure: Progression-free Survival
timeFrame: 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
measure: Overall Survival
timeFrame: From study entry to death or last contact, up to 5 years.
measure: Number of Participants With Episodes and Grade of Adverse Events as Assessed by Common Terminology for Adverse Events Version 3.0
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Los Angeles County-USC Medical Center
state: California
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: New Britain
country: United States
facility: The Hospital of Central Connecticut
state: Connecticut
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center-Gainesville
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Hinsdale
country: United States
facility: Hinsdale Hematology Oncology Associates Incorporated
state: Illinois
city: Hinsdale
country: United States
facility: Sudarshan K Sharma MD Limted-Gynecologic Oncology
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa/Holden Comprehensive Cancer Center
state: Iowa
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Health Care
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota/Masonic Cancer Center
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center/Levine Cancer Institute
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Cancer Center/Fairview Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Mayfield Heights
country: United States
facility: Hillcrest Hospital Cancer Center
state: Ohio
city: Mentor
country: United States
facility: Lake University Ireland Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Tulsa
country: United States
facility: Oklahoma Cancer Specialists and Research Institute-Tulsa
state: Oklahoma
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Dallas
country: United States
facility: Parkland Memorial Hospital
state: Texas
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center-Dallas
state: Texas
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: NRG Oncology
name: Jubilee Brown
role: PRINCIPAL_INVESTIGATOR
References: