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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00702884
First received: June 19, 2008
Last updated: February 2, 2010
Last verified: June 2009
  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
Genetic: TdT-mediated dUTP nick end labeling assay
Other: immunoenzyme technique
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Procedure: computed tomography
Procedure: dynamic contrast-enhanced magnetic resonance imaging
Procedure: positron emission tomography
Phase 2

Study Type: Interventional
Study Design: Masking: 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 National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival rate (complete response, partial response, and stable disease) as assessed by RECIST criteria at 24 weeks [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall response rate [ Designated as safety issue: No ]
  • Median overall survival time [ Designated as safety issue: No ]
  • Median progression-free survival time [ Designated as safety issue: No ]
  • Frequency and severity of adverse events [ Designated as safety issue: Yes ]
  • Change in mean vessel density [ Designated as safety issue: No ]
  • Quantitative assessment of proliferating tumor cells and apoptosis [ Designated as safety issue: No ]

Estimated Enrollment: 25
Study Start Date: June 2008
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To determine the progression-free survival rate (complete response, partial response, and stable disease as defined by RECIST criteria) 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 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
Genders Eligible for Study:   Both
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 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 and ALT ≤ 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 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 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00702884

Locations
United States, Ohio
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210-1240
Contact: Tanios Bekaii-Saab, MD    866-627-7616      
Sponsors and Collaborators
Ohio State University Comprehensive Cancer Center
Investigators
Principal Investigator: Tanios Bekaii-Saab, MD Ohio State University Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Tanios Bekaii-Saab, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00702884     History of Changes
Other Study ID Numbers: CDR0000597858, OSU-07121, OSU-2008C0028
Study First Received: June 19, 2008
Last Updated: February 2, 2010
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
recurrent esophageal cancer
stage III 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
Therapeutic Uses
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on April 20, 2014