Brivanib Alaninate in Treating Patients With Recurrent or Persistent Endometrial Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00888173|
Recruitment Status : Completed
First Posted : April 27, 2009
Results First Posted : November 6, 2017
Last Update Posted : December 6, 2017
|Condition or disease||Intervention/treatment||Phase|
|Endometrial Adenocarcinoma Endometrial Clear Cell Adenocarcinoma Endometrial Mixed Adenocarcinoma Endometrial Mucinous Adenocarcinoma Endometrial Serous Adenocarcinoma Endometrial Squamous Cell Carcinoma Endometrial Transitional Cell Carcinoma Endometrial Undifferentiated Carcinoma Recurrent Uterine Corpus Carcinoma||Drug: Brivanib Alaninate Other: Laboratory Biomarker Analysis||Phase 2|
I. To assess the activity of brivanib (brivanib alaninate) for patients with recurrent or persistent endometrial cancer with the frequency of patients who survive progression-free for at least 6 months after initiating therapy or have objective tumor response..
I. To determine the duration of progression-free survival and overall survival. II. To determine the nature and degree of toxicity of brivanib as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v)3.0 in this cohort of patients.
I. To determine whether activating mutations in fibroblast growth factor receptor 2 (FGFR2) are associated with progression-free survival status > 6 months following brivanib treatment, objective tumor response following brivanib treatment, or endometrioid histology.
II. To explore the associations between select biomarkers and response to brivanib (progression-free survival status > 6 months and objective tumor response), measures of clinical outcome (progression-free survival and overall survival) or disease status including histologic cell type: i) mutations in FGFR2 or phosphatase and tensin homolog (PTEN) in deoxyribonucleic acid (DNA) from formalin-fixed and paraffin-embedded (FFPE) tumor or normal blood cells; ii) immunohistochemical (IHC) expression of the FGFR family and ligands, steroid receptor isoforms or phosphorylated (p) v-akt murine thymoma viral oncogene homolog 1 (AKT) in FFPE tumor; iii) concentration or the change in the concentration of vascular endothelial growth factor (VEGF) or type IV collagen in pre-cycle 1, pre-cycle 2 and/or pre-cycle 3 plasma.
III. To explore the relationship among the panel of biomarkers evaluated in this cohort: i) mutations in FGFR2 or PTEN; ii) IHC expression of the FGFR family and ligands, steroid receptor isoforms or pAKT; iii) concentration or the change in the concentration of VEGF or type IV collagen.
Patients receive brivanib alaninate orally (PO) once daily (QD) on days 1-28. 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 (Clinical Trial)|
|Actual Enrollment :||45 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Evaluation of Brivanib (BMS582664), an Oral, Multitargeted Growth Factor Tyrosine Kinase Inhibitor in the Treatment of Recurrent or Persistent Endometrial Carcinoma|
|Actual Study Start Date :||July 6, 2009|
|Actual Primary Completion Date :||July 16, 2016|
|Actual Study Completion Date :||July 16, 2016|
Experimental: Treatment (brivanib alaninate)
Patients receive brivanib alaninate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Brivanib Alaninate
Other: Laboratory Biomarker Analysis
- Progression-free Survival > 6 Months [ Time Frame: For patients whose disease can be evaluated by physical examination, progression was assessed prior to each cycle for 6 months. ]Whether or not the patient survived progression-free for at least 6 months.
- Tumor Response [ Time Frame: If evaluated by physical exam, response was assessed prior to each cycle. If evaluated by CT or MRI, response was assessed during course of therapy. Overall time frame is up to 6 months. ]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.
- Duration of Overall Survival [ Time Frame: From entry into the study to death or the date of last contact, assessed up to 5 years ]Characterized graphically with Kaplan-Meier estimates and using descriptive statistics. The effect of cell type (type I versus type II endometrial cancers) on overall survival will be examined.
- Duration of Progression-free Survival [ Time Frame: Form study entry until disease progression, death or date of last contact, assessed up to 5 years ]Characterized graphically with Kaplan-Meier estimates and using descriptive statistics. The effect of cell type (type I versus type II endometrial cancers) on progression-free survival will be examined.
- Severity of Adverse Events as Assessed by CTCAE v3.0 Criteria [ Time Frame: Up to 5 years ]Adverse Events (grade 3 or higher)
- Activating Mutation in FGFR2 [ Time Frame: Up to 5 years ]Will be correlated with clinical measures of outcome such as tumor response, progression-free survival (PFS), and endometrioid histology.
- Change in Concentration of VEGF and Type IV Collagen [ Time Frame: Baseline to up to pre-course 3 ]Will be correlated with PFS, OS, tumor response, and histologic cell type.
- IHC Expression of FGFR Family and Ligands, Steroid Receptor Isoforms, and pAKT [ Time Frame: Up to 5 years ]Will be correlated with PFS, OS, tumor response, and histologic cell type.
- Mutations in FGFR2 and PTEN [ Time Frame: Up to 5 years ]Will be correlated with PFS, overall survival (OS), tumor response, and histologic cell type.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00888173
|Principal Investigator:||Matthew Powell||NRG Oncology|