Sunitinib in Treating Patients With Relapsed or Refractory Esophageal or Gastroesophageal Junction Cancer
RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
PURPOSE: This phase II trial is studying how well sunitinib works in treating patients with relapsed or refractory esophageal or gastroesophageal junction cancer.
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Mechanistic Radiographic and Biologic Phase 2 Single Agent Study of Sunitinib Malate in Relapsed/Refractory Esophageal and Gastroesophageal Cancers|
- Progression-free Survival Rate [ Time Frame: up to 24 weeks ]Complete response, partial response, and stable disease) as assessed by RECIST criteria at 24 weeks
- Overall Response Rate [ Time Frame: up to 4 years ]The Overall Response Rate (ORR) was assessed using Partial Response + Complete Response for patients. Response and progression was evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0.
- Median Overall Survival Time [ Time Frame: up to 4 years ]The median overall survival time will be reported using the 95% confidence intervals for the parameters.
- Median Progression-free Survival Time [ Time Frame: up to 4 years ]Progression free survival was measured as the time from start of treatment to the first measurement of tumor growth.
- Frequency and Severity of Adverse Events [ Time Frame: up to 4 years ]The National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for adverse event reporting.
- Change in Mean Vessel Density [ Time Frame: up to 4 years ]Quantitative assessment of proliferating tumor cells, and apoptosis, of the laboratory and radiographic correlates, the analyses will be purely explorative.
- Quantitative Assessment of Proliferating Tumor Cells and Apoptosis [ Time Frame: up to 4 years ]Biopsy sample taken from patients before and after treatment Apoptosis measures using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, which measures 3' nicked DNA. DNA is degraded in the early steps of apoptosis into low molecular weight (LMW) fragments and the production of single strand breaks in the high molecular weight DNA.Both of these features of apoptosis can be detected by labeling free 3'-OH termini with modified nucleotides, in our case this will be biotin-labeled dUTP. Terminal deoxynucleotidyl transferase (TdT) is an enzyme that labels blunt-ends of DNA breaks and can catalyze polymerization of nucleotides to free 3'-OH DNA ends in a template-independent manner. The newly incorporated nucleotides are detected by a secondary antibody, avidin-peroxidase. After substrate reaction, the stained cells can be detected and counted under a light microscope. Apoptotic cells will be fixed with formaldehyde which links LMW DNA
|Actual Study Start Date:||June 30, 2008|
|Study Completion Date:||December 30, 2013|
|Primary Completion Date:||September 17, 2013 (Final data collection date for primary outcome measure)|
Sunitinib 37.5 mg daily for a 4 week cycle
Drug: sunitinib malate
Sunitinib 37.5 mg daily for a 4 week cycle
- To determine the progression-free survival rate (complete response, partial response, and stable disease as defined by RECIST criteria [Response Evaluation Criteria in solid Tumors]) at 24 weeks in patients with relapsed or refractory esophageal or gastroesophageal junction cancer treated with sunitinib malate.
- To explore the predictive role of a hybrid imaging protocol that combines PET/CT (Positron emission tomography) scan simultaneously with dynamic contrast-enhanced MRI.
- Correlate quantitative changes in mean vessel density, alterations in tumor cell proliferation, and apoptosis in tumor biopsy specimens with clinical outcome in these patients.
- To evaluate the objective response as defined by RECIST criteria, median overall survival, and median progression-free survival of these patients.
- To evaluate the toxicities of sunitinib malate in these patients.
OUTLINE: Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo blood and tumor tissue sample collection periodically for correlative laboratory studies. Tumor tissue samples are assessed by immunohistochemistry and TUNEL for detection and quantitation of mean vessel density, proliferating tumor cells, and apoptosis. Tumor tissue samples are also assessed by immunohistochemistry for MAPK levels. Blood samples are analyzed by ELISA for VEGF, PlGF, sVEGFR2, and sVEGFR3 levels. Patients also undergo PET/CT scan and dynamic contrast-enhanced MRI periodically for correlative studies.
After completion of study treatment, patients are followed for at least 6 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00702884
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Tanios Bekaii-Saab, MD||Ohio State University|