Randomized Phase II Trial of Extended Neoadjuvant Therapy for Locally Advanced Adenocarcinoma of the Esophagus, Gastroesophageal Junction, and Gastric Cardia

Trial Information

Randomized Phase II Trial of Extended Neoadjuvant Therapy for Locally Advanced Adenocarcinoma of the Esophagus, Gastroesophageal Junction, and Gastric Cardia

OBJECTIVES:

Primary

- Assess and compare the pathologic complete response rate of sequential docetaxel,
oxaliplatin, and capecitabine followed by fluorouracil, oxaliplatin, and radiotherapy
versus fluorouracil, oxaliplatin, and radiotherapy alone in patients with potentially
resectable advanced adenocarcinoma of the esophagus, gastroesophageal junction, or
gastric cardia.

Secondary

- Assess the adverse event profile and safety of these regimens in this patient
population.

- Assess and compare the overall survival of patients treated with these regimens.

- Assess and compare the disease-free survival between treatment arms.

- Assess and compare the clinical tumor response rate of these proposed regimens when
administered before surgery between treatment arms.

- Evaluate the profiles of pharmacogenetic and proteomic marker measures over time, and
assess the association of changes in these biomarkers induced by these proposed
regimens with pathologic tumor response and other outcomes of interest.

- Evaluate the profiles of FDG PET/CT measures, including standardized uptake values and
% injected dose in the tumor volume over time, and assess the correlation of changes in
PET measures with pathologic tumor response and other outcomes of interest.

OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance
status (0-1 vs 2), and disease stage (II vs III/IVA). Patients are randomized to 1 of 2
treatment arms.

- Arm I: Patients receive docetaxel IV over 1 hour and oxaliplatin IV over 2 hours on day
1. Patients also receive oral capecitabine twice daily on days 1-14. Treatment repeats
every 21 days for 2 courses in the absence of disease progression or unacceptable
toxicity. After completion of the second course, patients receive fluorouracil* IV
continuously on days 1-5 and oxaliplatin IV over 2 hours on days 1, 15, and 29.
Patients also undergo radiotherapy** 5 days a week for 5.5 weeks in the absence of
disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion
of radiotherapy, patients undergo surgery.

- Arm II: Patients receive fluorouracil IV continuously on days 1-5 and oxaliplatin IV
over 2 hours on days 1, 15, and 29. Patients also undergo radiotherapy and then surgery
as in arm I.* NOTE: * Fluorouracil continuous IV infusion begins within 24 hours of
radiotherapy and ends within 24 hours of radiotherapy completion.

NOTE: ** Radiotherapy should begin within 2-6 weeks after completion of 2 courses of
docetaxel, oxaliplatin, and capecitabine.

Blood samples are collected at baseline and periodically during study for pharmacogenetic
(genetic polymorphisms along with drug target pathways) and proteomic markers (microRNA and
mRNA expression) studies. Tumor tissue samples from biopsy and surgery are also collected
for pharmacogenetic and proteomic markers studies and future correlative studies.

After completion of study therapy, patients are followed up every 3-6 months for 2 years.