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

Tony Bekaii-Saab

Status and phase

Completed

Phase 2

Conditions

Esophageal Cancer

Treatments

Drug: sunitinib malate

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00702884

NCI-2011-03148 (Registry Identifier)

OSU-07121

Details and patient eligibility

About

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.

Full 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.

Enrollment

25 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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)