This pilot phase II trial studies how well giving bevacizumab and combination chemotherapy together before surgery works in treating patients with locally advanced esophageal or stomach cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, and oxaliplatin work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab and combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.
PRIMARY OBJECTIVES: I. To investigate two-year disease-free survival in patients with resectable esophageal and gastroesophageal (GE) junction cancer treated with perioperative bevacizumab and leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX). SECONDARY OBJECTIVES: I. To assess, by pathological examination after surgical resection, complete and partial response to neoadjuvant therapy. II. To characterize overall and progression free survival. III. To compare baseline and post-chemotherapy/bevacizumab tissues for biomarkers predicting response or resistance to this approach. IV. To investigate safety in this setting. OUTLINE: NEOADJUVANT THERAPY: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on day 1. Patients also receive FOLFOX chemotherapy comprising oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46 hours on days 1-2. Treatment with bevacizumab repeats every 2 weeks for 4 courses and treatment with FOLFOX repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. SURGERY: Patients then undergo planned surgical resection 4-6 weeks after 6 courses of chemotherapy and at least 8 weeks since the last dose of bevacizumab. ADJUVANT THERAPY: Beginning 8-10 weeks after surgery, patients receive bevacizumab IV, oxaliplatin IV, leucovorin calcium IV, and fluorouracil IV as in neoadjuvant therapy. Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Given IV
Given IV
Given IV
Given IV
Undergo surgical resection
Correlative studies
Case Western Reserve University
Cleveland, Ohio, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States
Disease-free Survival
To investigate 2 year disease free survival in pts with resectable esophageal and GE junction cancer treated with perioperative bevaciumab and FOLFOX
Time frame: 2 years
Complete and Partial Response to Neoadjuvant Therapy Based on the Response Evaluation Criteria in Solid Tumors (RECIST)
To assess, by path examination after surgical resection, complete and partial response to neoadjuvant therapy. Characterized using proportions and 95% confidence intervals.
Time frame: Up to 3 years
Overall Survival
Characterized using Kaplan-Meier curves.
Time frame: 4.5 years
Progression Free Survival
Characterized using Kaplan-Meier curves. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions and a 5 mm absolute increase, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: 3 years
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