A Randomized Phase II Trial of Sunitinib Plus Capecitabine Versus Capecitabine Alone (With the Potential for Crossover) for Elderly and/or Poor Performance Status Patients With Metastatic Adenocarcinoma of the Esophagus or Gastroesophageal Junction
A Randomized Phase II Trial of Sunitinib Plus Capecitabine Versus Capecitabine Alone (With the Potential for Crossover) for Elderly and/or Poor Performance Status Patients With Metastatic Adenocarcinoma of the Esophagus or Gastroesophageal Junction
RATIONALE: Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sunitinib malate 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. It is not yet known whether capecitabine is more effective when given alone or together with sunitinib malate in treating patients with metastatic esophageal cancer or gastroesophageal junction cancer.
PURPOSE: This randomized phase II trial is studying how well capecitabine works compared with capecitabine given together with sunitinib malate as first-line therapy in treating patients with metastatic cancer of the esophagus or gastroesophageal junction.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter study. Patients are stratified according to gender (male vs female), ECOG performance status (0 vs 1 vs 2), and age (≥ 65 years vs < 65 years). Patients are randomized to 1 of 2 treatment arms.
In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Tumor tissue samples are collected at baseline for evaluation of protein markers as possible predictors of tumor response to this regimen. Samples are analyzed by IHC for expression levels of markers
After completion of study therapy, patients are followed periodically for 3 years.
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed adenocarcinoma of the esophagus or gastroesophageal junction
Measurable disease with ≥ 1 lesion whose longest diameter can be accurately measured as ≥ 2.0 cm by conventional techniques or ≥ 1.0 cm by spiral CT
Not a candidate for a conventional multi-drug chemotherapy regimen with fairly standard dosing (i.e., patient is able to tolerate at least 80% of standard dosing)
No known CNS metastases
PATIENT CHARACTERISTICS:
ECOG performance status (PS) 0-2 and age ≥ 65 years OR PS 2 and age ≥ 18 years but < 65 years
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Total bilirubin normal
Alkaline phosphatase ≤ 2 times upper limit of normal (ULN)
Creatinine ≤ 1.5 times ULN
Creatinine clearance ≥ 60mL/min
AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver metastases)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Willing to provide tissue samples for central review and research purposes
Able to swallow pills
No immunocompromised patients (other than related to the use of corticosteroids), including patients known to be HIV-positive
No co-morbid systemic illnesses or other severe concurrent disease that, in the judgment of the investigator, would make the patient inappropriate for this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
No uncontrolled intercurrent illness including, but not limited to, any of the following:
No NYHA class III or IV heart failure
No uncontrolled hypertension except at the discretion of treating oncologist
No other active malignancy except for nonmelanoma skin cancer or carcinoma in situ of the cervix
No known dihydropyrimidine dehydrogenase deficiency (DPD)
PRIOR CONCURRENT THERAPY:
No prior chemotherapy, radiotherapy, immunotherapy, or biological therapy for recurrent or metastatic cancer
No prior sunitinib malate
No prior radiotherapy to > 30% of the marrow cavity at any time
More then 4 weeks since prior major surgery
At least 12 days since prior and no concurrent CYP3A4 inducers, including rifampin, rifabutin, carbamazepine, phenobarbital, phenytoin, St. John's wort, efavirenz, and tipranavir
At least 7 days since prior and no concurrent CYP3A4 inhibitors, including azole antifungals (ketoconazole, itraconazole), clarithromycin, erythromycin, diltiazem, verapamil, HIV protease inhibitors (indinavir, saquinavir, ritonavir, atazanavir, nelfinavir), and delavirdine
No other concurrent specific treatment (other than hormonal therapy) in patients with a history of prior malignancy
Hartford, Connecticut 06105, United States
Ottawa, Illinois 61350, United States
Peoria, Illinois 61615, United States
Beech Grove, Indiana 46107, United States
Des Moines, Iowa 50309, United States
Des Moines, Iowa 50314, United States
Wichita, Kansas 67214, United States
Dearborn, Michigan 48123-2500, United States
Grosse Pointe Woods, Michigan 48236, United States
Minneapolis, Minnesota 55407, United States
Robbinsdale, Minnesota 55422-2900, United States
St Louis, Missouri 63141, United States
Billings, Montana 59102, United States
Missoula, Montana 59807, United States
Wilkes-Barre, Pennsylvania 18711, United States
Spartanburg, South Carolina 29303, United States
Sioux Falls, South Dakota 57117-5039, United States