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

Esophageal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00702884
• Other study ID #: OSU-07121
• Secondary ID: NCI-2011-03148
• Status: Completed
• Phase: Phase 2
• First received: June 19, 2008
• Last updated: April 20, 2015
• Start date: June 2008
• Est. completion date: December 2013

Study information

• Verified date: April 2015
• Source: Ohio State University Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: December 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

Drug:
• sunitinib malate
Sunitinib 37.5 mg daily for a 4 week cycle

Locations

Country	Name	City	State
United States	Ohio State University Medical Center	Columbus	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Tony Bekaii-Saab	Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival rate (complete response, partial response, and stable disease) as assessed by RECIST criteria at 24 weeks		up to 4 years	No
Secondary	Overall response rate		up to 4 years	No
Secondary	Median overall survival time		up to 4 years	No
Secondary	Median progression-free survival time		up to 4 years	No
Secondary	Frequency and severity of adverse events		up to 4 years	Yes
Secondary	Change in mean vessel density		up to 4 years	No
Secondary	Quantitative assessment of proliferating tumor cells and apoptosis		up to 4 years	No

External Links

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