Paclitaxel is known to be active as a single and combination agent in esophageal cancer, and has also been demonstrated to have anti-angiogenic properties in weekly dosing regimens. Sunitinib malate is an anti-angiogenic drug with the potential to improve responses when combined with chemotherapy, as demonstrated with other regimens in similar settings. We believe that the combination of paclitaxel and sunitinib malate offer great promise in the treatment of advanced esophageal cancer.
OUTLINE: This is a multi-center study. Treatment will be administered on an outpatient basis. Chemotherapy will be administered in a 28-day treatment cycle. The 28 days of treatment with paclitaxel and sunitinib malate (plus the time required to recover if toxicity is encountered) is defined as a cycle. * Paclitaxel 90 mg/m2 IV on days 1, 8 and 15. * Sunitinib malate 37.5 mg orally, daily. After 4 cycles, paclitaxel will be discontinued and patients will continue on sunitinib malate until disease progression, unacceptable toxicity, or physician discretion. Performance Status: ECOG (Eastern Cooperative Oncology Group) performance status 0 to 2 Life expectancy: Not specified Hematopoietic: * International Normalized Ratio (INR) \< 1.2 * Partial Thromboplastin Time (PTT) \< 1.5 x Upper Limit of Normal (ULN) * Platelets \> 100 K/mm3 * Hemoglobin \> 8 g/dL * Absolute Neutrophil Count (ANC) \> 1.0 K/mm3 Hepatic: * Aspartate transaminase (AST) ≤ 2.5 x ULN, or ≤ 5.0 x ULN if the transaminase elevation is due to known liver metastases. * Alanine transaminase (ALT) ≤ 2.5 x ULN, or ≤ 5.0 x ULN if the transaminase elevation is due to known liver metastases. * Total bilirubin \< 2.0 x ULN Renal: * Serum creatinine ≤ 2 x ULN or a calculated creatinine clearance (using Cockcroft-Gault formula) \> 50 cc/min Cardiovascular: * No history of unstable angina, myocardial infarction, coronary artery bypass grafting surgery within 12 months prior to registration for protocol therapy. Patients may be on anti-anginal medications, but must be stable on those medications for at least 6 months. * No history of New York Heart Association class II or greater congestive heart failure. Pulmonary: * Not specified
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
28
Sunitinib malate 37.5 mg orally, daily
Paclitaxel 90 mg/m2 IV on days 1, 8 and 15.
Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States
Rush-Presbyterian St. Luke's Medical Center
Chicago, Illinois, United States
Progression Free Survival Rate at 24 Weeks
To determine the rate of non-progressive disease at 24 weeks from the first dose of the combination of sunitinib malate and paclitaxel in advanced esophageal carcinoma, where progression is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions
Time frame: 24 weeks
Response Rate
To determine the response rate for the combination of sunitinib malate and paclitaxel in advanced esophageal carcinoma per RECIST criteria.
Time frame: 6 months
Overall Survival
To determine the one year overall survival rate for the combination of sunitinib malate and paclitaxel in advanced esophageal carcinoma
Time frame: 12 months
Progression-Free Survival
To determine the time to progression for the combination of sunitinib malate and paclitaxel in advanced esophageal carcinoma per RECIST criteria.
Time frame: 12 months
Toxicity Profile
Determine the most frequent toxicities associated with the treatment regimen, per the CTCAE version 3 (Common Toxicity Criteria for Adverse Events) criteria.
Time frame: 16 months
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