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

Malignant Ovarian Epithelial Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00748657
• Other study ID #: NCI-2009-00611
• Secondary ID: NCI-2009-00611CD
• Status: Completed
• Phase: Phase 2
• Start date: September 22, 2008
• Est. completion date: January 31, 2013

Study information

• Verified date: July 2019
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: January 31, 2013
• Est. primary completion date: January 31, 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Leydig Cell Tumor
• Malignant Ovarian Epithelial Tumor
• Neoplasms
• Ovarian Granulosa Cell Tumor
• Ovarian Gynandroblastoma
• Ovarian Neoplasms
• 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
• Sertoli-Leydig Cell Tumor

Intervention

Biological:
• Bevacizumab
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Locations

Country	Name	City	State
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	University of Colorado Hospital	Aurora	Colorado
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Miami Valley Hospital	Dayton	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Northeast Georgia Medical Center-Gainesville	Gainesville	Georgia
United States	Hartford Hospital	Hartford	Connecticut
United States	Hinsdale Hematology Oncology Associates Incorporated	Hinsdale	Illinois
United States	Sudarshan K Sharma MD Limted-Gynecologic Oncology	Hinsdale	Illinois
United States	M D Anderson Cancer Center	Houston	Texas
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Los Angeles County-USC Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Lake University Ireland Cancer Center	Mentor	Ohio
United States	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	University of Massachusetts Medical School	Worcester	Massachusetts
United States	University of Massachusetts Memorial Health Care	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	NRG Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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.
Secondary	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