- Compare the progression-free survival of elderly (age ≥ 65 years) and/or poor performance status patients with metastatic adenocarcinoma of the esophagus or gastroesophageal junction treated with capecitabine with verus without sunitinib malate.
- Report other indicators of efficacy with these regimens, including the confirmed response rate, overall survival, time to tumor progression, duration of response, and time to treatment failure.
- Compare the adverse event profiles of these regimens in these patients.
- Explore whether certain key proteins associated with anti-VEGF therapy are able to predict tumor response.
- Bank paraffin-embedded tissue blocks or slides, and blood products for future studies.
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.
- Arm I: Patients receive oral capecitabine twice daily on days 1-14. Patients experiencing disease progression may crossover to arm II at the physician's discretion.
- Arm II: Patients receive oral capecitabine as in arm 1 and oral sunitinib malate once daily on days 1-21.
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.
- Histologically or cytologically confirmed adenocarcinoma of the esophagus or gastroesophageal junction
- Metastatic disease
- Unresectable disease with no curative options
- 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)
- Patients who have been offered and declined conventional multi-drug chemotherapy are eligible
- No known CNS metastases
- 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:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situations that would limit compliance with study requirements
- 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
- Prior chemotherapy or radiotherapy are allowed if they had been administered as adjuvant or neoadjuvant therapy and a complete surgical resection of the original cancer had been achieved
- 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
Last updated: 01/20/2013
NCT ID: NCT00891878