Trial Information

Randomized Phase II Trial of PET Scan-Directed Combined Modality Therapy in Esophageal Cancer

OBJECTIVES:

Primary

- To induce a complete pathologic response (pCR) rate of 20% in positron emission
tomography (PET) scan non-responders treated with either induction FOLFOX or
carboplatin/paclitaxel, who then crossover to the other regimen during radiotherapy.

Secondary

- To compare PET/CT response between induction treatment arms.

- To compare pCR between induction treatment arms among PET/CT scan responders.

- To directly compare pCR between induction treatment arms among non-responders if both
treatment regimens are found to be efficacious.

- To determine 8-month progression-free survival (PFS) in PET/CT scan responders, and in
non-responders treated with alternative crossover chemoradiotherapy.

- Estimate the PFS and overall survival (OS) curves, overall and among PET responders and
PET/CT non-responders by induction treatment.

- To determine the rate of postoperative anastomotic leak after neoadjuvant chemotherapy
followed by chemoradiation.

- To evaluate immunohistochemistry and RT-PCR of ERCC1, and genetic polymorphisms of
ERCC1, XPD, and XRCC1.

- To evaluate status and levels of methylation of nine candidate biomarker genes as well
as expression levels of selected specific microRNAs, which will be correlated with
chemoradiation response.

- To compare the quality of life (QOL) of responders and nonresponders (as determined by
PET/CT scanning) to presurgical treatment for esophageal cancer, in terms of global
QOL, physical symptoms, physical functioning, and emotional well-being.

- To examine the association between OS and QOL in esophageal cancer patients treated
with chemotherapy, chemoradiation therapy, and surgery.

OUTLINE: This is a multicenter study. Patients are stratified according to T-stage (T1-2 vs
T3-4) and nodal status (N0 vs N+). Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive modified FOLFOX-6 therapy comprising oxaliplatin IV over 2
hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously
on days 1-5. Treatment repeats every 14 days for 3 courses. Patients then undergo
PET/CT scan. Patients with responsive disease (tumor metabolic activity decreased by ≥
35%) receive 3 additional courses of FOLFOX-6 therapy and undergo concurrent
radiotherapy (RT) (3D-conformal or intensity-modulated) once daily, 5 days a week, for
approximately 6 weeks. Patients without responsive disease (tumor metabolic activity
did not decrease by 35%) cross over to arm II during RT.

- Arm II: Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 1 hour
on days 1 and 8. Treatment repeats every 21 days for 2 courses. Patients then undergo
PET/CT scan. Patients with responsive disease (tumor metabolic activity decreases ≥
35%) continue to receive carboplatin IV over 30 minutes and paclitaxel IV over 1 hour
once weekly for 5 weeks and undergo RT (3D-conformal or intensity-modulated) once a
day, 5 days a week, for approximately 6 weeks. Patients without responsive disease
(metabolic activity did not decrease by 35%) cross over to arm I during RT.

Within 4-10 weeks after completion of neoadjuvant chemoradiotherapy, patients undergo
surgery at the discretion of the treating team.

Patients may undergo blood sample collection at baseline and periodically during study for
correlative studies. Patients may also complete quality-of-life questionnaires at baseline
and periodically during study.

After completion of study therapy, patients are followed up periodically for 5 years.