Clinical trial NCT00702884: Sunitinib in Treating Patients With Relapsed or Refractory Esophageal or Gastroesophageal Junction Cancer
Official title: A Mechanistic Radiographic and Biologic Phase 2 Single Agent Study of Sunitinib Malate in Relapsed/Refractory Esophageal and Gastroesophageal Cancers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Esophageal Cancer
Keywords: recurrent esophageal cancer
stage IIIA esophageal cancer
stage IIIB esophageal cancer
stage IIIC esophageal cancer
stage IV esophageal cancer
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2008-06-20
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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)

Primary outcomes:
measure: Progression-free Survival Rate
timeFrame: up to 24 weeks
Secondary outcomes:
measure: Overall Response Rate
timeFrame: up to 4 years
measure: Median Overall Survival Time
timeFrame: up to 4 years
measure: Median Progression-free Survival Time
timeFrame: up to 4 years
measure: Frequency and Severity of Adverse Events
timeFrame: up to 4 years
measure: Change in Mean Vessel Density
timeFrame: up to 4 years
measure: Quantitative Assessment of Proliferating Tumor Cells and Apoptosis
timeFrame: up to 4 years
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
Study officials:
affiliation: Ohio State University
name: Tanios Bekaii-Saab, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wu C, Mikhail S, Wei L, Timmers C, Tahiri S, Neal A, Walker J, El-Dika S, Blazer M, Rock J, Clark DJ, Yang X, Chen JL, Liu J, Knopp MV, Bekaii-Saab T. A phase II and pharmacodynamic study of sunitinib in relapsed/refractory oesophageal and gastro-oesophageal cancers. Br J Cancer. 2015 Jul 14;113(2):220-5. doi: 10.1038/bjc.2015.197. Epub 2015 Jul 7.