Sunitinib in Treating Patients With Relapsed or Refractory Esophageal or Gastroesophageal Junction Cancer
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|ClinicalTrials.gov Identifier: NCT00702884|
Recruitment Status : Completed
First Posted : June 20, 2008
Results First Posted : March 21, 2017
Last Update Posted : March 21, 2017
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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.
|Condition or disease||Intervention/treatment||Phase|
|Esophageal Cancer||Drug: sunitinib malate||Phase 2|
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Mechanistic Radiographic and Biologic Phase 2 Single Agent Study of Sunitinib Malate in Relapsed/Refractory Esophageal and Gastroesophageal Cancers|
|Actual Study Start Date :||June 30, 2008|
|Actual Primary Completion Date :||September 17, 2013|
|Actual Study Completion Date :||December 30, 2013|
Sunitinib 37.5 mg daily for a 4 week cycle
Drug: sunitinib malate
Sunitinib 37.5 mg daily for a 4 week cycle
- 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
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
Histologically confirmed esophageal or gastroesophageal junction carcinoma that is not amenable to curative surgery or other curative therapy
- Advanced, relapsed or refractory disease
- Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan
- No known brain metastases
- ECOG (Eastern Cooperative Oncology Group) performance status 0-1
- Life expectancy > 12 weeks
- WBC ≥ 3,000/μL
- Absolute neutrophil count ≥ 1,500/μL
- Platelet count ≥ 100,000/μL
- Serum calcium ≤ 12.0 mg/dL
- Total bilirubin normal
- AST (aspartate aminotransferase) and ALT (Alanine Aminotransferase) ≤ 2.5 times upper limit of normal
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception prior to, during, and for 28 days after completion of study treatment
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib malate
- No ongoing cardiac dysrhythmias ≥ grade 2, atrial fibrillation of any grade, or prolongation of the QTc (corrected QT interval) interval to > 450 msec (for males) or > 470 msec (for females)
- No hypertension that cannot be controlled by medications (i.e., systolic/diastolic blood pressure > 150/100 mm Hg despite optimal medical therapy)
- No myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within the past 12 months
- No cerebrovascular accident or transient ischemic attack within the past 12 months
- No pulmonary embolism within the past 12 months
- No condition that would impair the ability to swallow and retain sunitinib malate tablets (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease)
- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
- No serious or nonhealing wound, ulcer, or bone fracture
- No pre-existing thyroid abnormality that cannot be maintained in the normal range with medication
- No concurrent uncontrolled illness including, but not limited to, ongoing or active infection or psychiatric illness/social situation that would limit compliance with study requirements
PRIOR CONCURRENT THERAPY:
- Recovered from prior therapy
- At least 4 weeks since prior radiotherapy or major surgery
- At least 4 weeks since prior chemotherapy (6 weeks for mitomycin C, carmustine, or alkylating agents)
- No more than 6 prior courses of an alkylating agent
- No more than 450 mg/m² of prior doxorubicin hydrochloride or 900 mg/m² of prior epirubicin hydrochloride
- No more than 2 lines of prior therapy in the metastatic setting
- No prior anti-VEGF monoclonal antibodies, such as bevacizumab or aflibercept
- No prior tyrosine kinase inhibitors with similar targets (e.g., sorafenib tosylate or axitinib)
- No other concurrent investigational agents
No concurrent therapeutic doses of coumarin-derivative anticoagulants, such as warfarin
- Warfarin at doses of ≤ 2 mg daily are allowed for prophylaxis of thrombosis
- Low molecular weight heparin allowed provided PT/INR (Prothrombin time and international normalized ratio) is ≤ 1.5
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No concurrent agents with proarrhythmic potential (e.g., terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, and flecainide)
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): NCT00702884
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Tanios Bekaii-Saab, MD||Ohio State University|
Publications of Results:
|Responsible Party:||Tony Bekaii-Saab, Principal Investigator, Ohio State University Comprehensive Cancer Center|
|Other Study ID Numbers:||
NCI-2011-03148 ( Registry Identifier: Clinical Trials Reporting Program (CTRP) )
|First Posted:||June 20, 2008 Key Record Dates|
|Results First Posted:||March 21, 2017|
|Last Update Posted:||March 21, 2017|
|Last Verified:||January 2017|
recurrent esophageal cancer
stage IIIA esophageal cancer
stage IIIB esophageal cancer
stage IIIC esophageal cancer
stage IV esophageal cancer
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Angiogenesis Modulating Agents
Physiological Effects of Drugs
Protein Kinase Inhibitors
Molecular Mechanisms of Pharmacological Action