This phase I trial is studying the side effects and best dose of erlotinib hydrochloride when given together with oxaliplatin, fluorouracil, and radiation before surgery and alone after surgery in treating patients with locally advanced cancer of the esophagus and gastroesophageal junction. Drugs used in chemotherapy, such as oxaliplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with erlotinib hydrochloride and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving erlotinib hydrochloride after surgery may kill any tumor cells that remain after surgery
OBJECTIVES: I. The primary aim of this phase I study is to evaluate the safety of multi-drug chemotherapy (with the addition of an anti-epidermal growth factor receptor \[EGFR\] agent erlotinib \[erlotinib hydrochloride\]) and concomitant radiotherapy followed by resection and consolidative erlotinib for the treatment of locally advanced esophageal cancer as judged by the dose limiting toxicities. Correlative endpoints include an analysis of pre-treatment tumor cyclin D1 expression and EGFR expression/amplification. III. Correlate pathologic complete response with changes in fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)-computed tomography (CT) - pre and post-chemoradiation. OUTLINE: This is a dose escalation study of erlotinib hydrochloride CHEMORADIOTHERAPY: Patients undergo radiation therapy once daily (QD), 5 days a week and receive fluorouracil intravenously (IV) continuously and erlotinib hydrochloride orally (PO) QD on days 1-38. Patients also receive oxaliplatin IV over 2 hours on days 1, 15, and 29. SURGERY: Within 4-8 weeks after completion of chemoradiotherapy, patients with potentially resectable disease (i.e., complete response, partial response, or stable disease) undergo surgery to remove the tumor. CONSOLIDATION CHEMOTHERAPY: Within 2-4 weeks after surgery, patients with tumors that demonstrate positive immunohistochemistry for EGFR and/or cyclin D1 (in the pretreatment biopsy or in the residual tumor in the esophagectomy specimen) receive consolidation chemotherapy comprising erlotinib hydrochloride PO QD for 12 weeks. After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
Given PO
Given IV
Given IV
Undergo radiotherapy
Undergo surgical resection
Correlative study
Correlative study
Correlative study
Correlative study
Correlative study
Undergo F18 PET and CT scan
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
Toxicity rate of combination chemotherapy followed by surgery and erlotinib hydrochloride
Toxicity will be determined using the revised National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 3.0 for Toxicity and Adverse Event Reporting (CTCAE v3.0). The dose limiting toxicity will be defined as any of the following that can be attributal to therapy: Any grade 4 neutropenia and or any grade 4 thrombocytopenia, or any \>= grade 3 non-hematologic toxicity that results in a greater than 3 day interruption of therapy.
Time frame: Approximately 6 months
Time to progression
Time frame: Approximately 4 years
Survival
Time frame: Approximately 4 years
Specific characteristics that predict complete response rate (e.g., EGFR status, EGFR amplification, and cyclin D1 expression)
Time frame: Over 4 years
Specific characteristics that predict complete response rate (e.g., EGFR status, EGFR amplification, and cyclin D1 expression)
Time frame: Approximately 1 year
Test the predictive value of FDG-PET-CT imaging in identifying patients who will have a complete response
Time frame: Approximately 1 year
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.