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Sunitinib in Treating Patients With Relapsed or Refractory Esophageal or Gastroesophageal Junction Cancer

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Tony Bekaii-Saab, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00702884
First received: June 19, 2008
Last updated: January 31, 2017
Last verified: January 2017
  Purpose

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 Intervention Phase
Esophageal Cancer Drug: sunitinib malate Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Tony Bekaii-Saab, Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Enrollment: 25
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)
Arms Assigned Interventions
Experimental: Sunitinib
Sunitinib 37.5 mg daily for a 4 week cycle
Drug: sunitinib malate
Sunitinib 37.5 mg daily for a 4 week cycle
Other Names:
  • Sutent
  • SU011248 L-Malate salt
  • SU010398
  • PHA-290940AD
  • SU011248

Detailed Description:

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00702884

Locations
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Tony Bekaii-Saab
Pfizer
Investigators
Principal Investigator: Tanios Bekaii-Saab, MD Ohio State University
  More Information

Additional Information:
Publications:
Responsible Party: Tony Bekaii-Saab, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00702884     History of Changes
Other Study ID Numbers: OSU-07121
NCI-2011-03148 ( Registry Identifier: Clinical Trials Reporting Program (CTRP) )
Study First Received: June 19, 2008
Results First Received: February 4, 2016
Last Updated: January 31, 2017

Keywords provided by Tony Bekaii-Saab, Ohio State University Comprehensive Cancer Center:
recurrent esophageal cancer
stage IIIA esophageal cancer
stage IIIB esophageal cancer
stage IIIC esophageal cancer
stage IV esophageal cancer

Additional relevant MeSH terms:
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Sunitinib
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on August 18, 2017