This phase II trial studies the side effects and how well cediranib maleate works in treating patients with endometrial cancer that has failed to respond to initial chemotherapy or has come back after surgery, radiation therapy, or other forms of treatment. Cediranib maleate may stop the growth of tumor cells by blocking proteins made by tumors that can stimulate growth of tumor cells as well as blood vessels in and around tumors.
PRIMARY OBJECTIVES: I. To assess the activity of cediranib (cediranib maleate) in patients with either persistent or recurrent endometrial carcinoma. II. To determine the frequency and degree of toxicity of cediranib as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version (v.)4.0 in this cohort of patients. SECONDARY OBJECTIVES: I. To determine the duration of progression-free survival and overall survival. II. To estimate the probability of response without restriction on the duration of response documentation since study enrollment. TERTIARY OBJECTIVES: I. To determine if the response to cediranib correlates with high-expression of its receptor targets (e.g., vascular endothelial growth factor receptor \[VEGFR\] \[1, 2, 3\] and platelet derived growth factor receptor \[PDGFR\]). II. To determine if the response to cediranib correlates with high endogenous circulating plasma levels of VEGFA, low-levels of its endogenous inhibitor, soluble fms-related tyrosine kinase 3 (sFlt-1) (the truncated, circulating portion of VEGFR-1), or circulating tissue factor (TF) or circulating prostate apoptosis response-4 (Par-4), both potential markers of tumor progression. III. To determine if a high-expression of VEGFA on pre-treatment tumor specimens correlates with response to cediranib. IV. To determine if expression of phosphorylated mitogen activated protein kinase (ERK) 1 and 2, c-Jun, signal transducer and activator of transcription 3 (Stat3), protein kinase C (PKC), and phosphorylated ribosomal protein S6 (p70S6) kinase correlates with resistance or sensitivity to cediranib. OUTLINE: Patients receive cediranib maleate orally (PO) daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
53
Given PO
Correlative studies
Providence Saint Joseph Medical Center/Disney Family Cancer Center
Burbank, California, United States
Palo Alto Medical Foundation-Gynecologic Oncology
Mountain View, California, United States
Hartford Hospital
Hartford, Connecticut, United States
The Hospital of Central Connecticut
New Britain, Connecticut, United States
Sarasota Memorial Hospital
Sarasota, Florida, United States
Incidence of Adverse Effects as Assessed by the National Cancer Institute CTCAE v. 4.0
Adverse Events (Grade 3 or higher)
Time frame: Up to 5 years
Tumor Response
Complete and Partial Tumor Response by RECIST 1.1. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall response (OR) = CR + PR.
Time frame: For diesease evaluated by physical examination, response was assessed prior to each cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle from enrollment until stopping study therapy. The average time on study is 3 mnths
Progression-free Survival (PFS) = > 6 Months
Number of participants who survived for at least 6 months. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v.1.0) as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: For disease evaluated by physical examination, progression was assessed prior to each cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle. Evaluated from time of enrollment until progression or death, up to 5 years
Overall Survival
The observed length of life from entry into the study to death or the date of last contact.
Time frame: From study entry to death or last contact, up to 5 years.
Progression Free Survival
Time until disease progression, death, or date of last contact.
Time frame: Disease that can be assessed by physical exam should be evaluated every cycle. disease assessed by imaging should be evaluated every other cycle. Time frame to determine the date of progression is from the date of enrollment up to 5 years after enrollment
Response Without Regard to the Time of Documented Response
Complete and partial tumor response by RECIST 1.1
Time frame: Tumor responses with time restriction starts at enrollment and goes to 6 months after enrollment or until pt. off study therapy,whichever occurs first. Without time restriction starts at enrollment,lasts until off study therapy, median duration = 2.63 mth
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Central Georgia Gynecologic Oncology
Macon, Georgia, United States
Rush University Medical Center
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Sudarshan K Sharma MD Limted-Gynecologic Oncology
Hinsdale, Illinois, United States
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...and 77 more locations