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A Mechanistic Radiographic and Biologic Phase 2 Single Agent Study of Sunitinib Malate in Relapsed/Refractory Esophageal and Gastroesophageal Cancers

Phase 2
18 Years
Open (Enrolling)
Esophageal Cancer

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Trial Information

A Mechanistic Radiographic and Biologic Phase 2 Single Agent Study of Sunitinib Malate in Relapsed/Refractory Esophageal and Gastroesophageal Cancers



- 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


- 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

- 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.

Inclusion Criteria


- 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 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

- 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


- 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

- No other concurrent investigational agents

- No concurrent therapeutic doses of coumarin-derivative anticoagulants, such as

- 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)

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival rate (complete response, partial response, and stable disease) as assessed by RECIST criteria at 24 weeks

Safety Issue:


Principal Investigator

Tanios Bekaii-Saab, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University Comprehensive Cancer Center



Study ID:




Start Date:

June 2008

Completion Date:

Related Keywords:

  • Esophageal Cancer
  • recurrent esophageal cancer
  • stage III esophageal cancer
  • stage IV esophageal cancer
  • Esophageal Diseases
  • Esophageal Neoplasms



Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center Columbus, Ohio  43210-1240