CaLGB 80803 is a phase ii study that is designed to evaluate the early assessment of
chemotherapy responsiveness by metabolic imaging to direct further therapy in
patients with esophageal cancer in order to improve their response to therapy as
demonstrated by pCR rates and PFS.
if PeT-directed therapy is shown to enhance outcomes among patients undergoing
multimodality therapy for esophageal cancer in this phase ii study, this approach
could be used to introduce newer regimens and targeted therapies into the
armamentarium of systemic therapies for this disease. Since the standard systemic
therapy for esophageal cancer remains undefined, there is room to evaluate new
therapies using metabolic imaging as an early evaluation of potential response. This
PeT-directed approach would need to be validated further in a randomized Phase iii
trial to determine if the early change in therapy impacts on PFS and overall survival.
Finally, this randomized Phase ii trial of two well-established chemotherapy regimens
used as induction therapy followed by combination with pre-operative radiotherapy
allows for a secondary analysis of response outcomes among patients receiving either
carboplatin/paclitaxel or FoLFoX6 as initial regimens. outcome measures such as
PeT response to induction chemotherapy, pCR after pre-operative therapy in both
the PeT non-responder and responder groups, and PFS for each treatment group will
be reported. While this is not a head-to-head comparison, this study can establish
these outcome measures for each of these regimens either in the upfront induction
therapy setting or as cross-over salvage regimens for PeT non-responders. as PeT
responsiveness is an integral biomarker in this study, all PeT scans will undergo real
time, central radiologic review by the CaLGB imaging Core Lab. additionally, the
pathology specimen will be centrally reviewed by the CaLGB Pathology Coordinating
Documentation of Disease
1. Surgically resectable, histologically confirmed esophageal adenocarcinoma, including
Siewert GE junction adenocarcinomas Types 1 and 2.
2. T1N1-3M0 or T2-4NanyM0 as determined by EUS and PET/CT (histologic confirmation
of lymph involvement is not required). All disease (tumor and nodes) must be both
surgically resectable and capable of containment in a radiotherapy field. No T4 tumor with
clear evidence of invasion of the vertebral column, heart, great vessels or tracheobronchial
3. All patients must have locoregional staging determined by endoscopic ultrasound (EUS) if
technically feasible. Endoscopy reports should clearly state both the T and N stage.
4. No evidence of distant metastases (as determined by EUS or PET/CT).
5. Patients with cervical, supraclavicular or other nodal disease that is either not included in
the radiation field or is not able to be resected at the time of esophagectomy are not
6. Patient must have pre-resection tissue available for central pathology review, in case
that the patient has a pCR at the time of surgical resection to confirm diagnosis.
Baseline PET Scan
Patients must have an FDG-avid tumor with a maximum standard uptake value (SUVmax) of
>= 5.0 on baseline PET/CT scan of primary tumor. Baseline PET/CT scan should be performed
as described in Section 11.1. If it is necessary to repeat baseline PET/CT scan, reimbursement
information is available in Section 7.1.
1. No prior malignancy within 5 years of registration, with the exception of basal or
squamous cell skin cancers, or in situ bladder or cervical cancer. Patients with prior
malignancy treated with surgery only and disease free for more than 5 years are eligible.
However, no prior thoracic RT or abdominal RT or chemotherapy allowed.
2. No known contraindication to the use of 5-FU, taxanes, or platinum compounds.
3. No history of severe hypersensitivity reaction to Cremophor(RegisteredTM) EL.
Age and Performance Status
1. Age >=18 years of age
2. ECOG Performance Status 0-1.
Patient must be non-pregnant and non-nursing. Women of child bearing potential must have a
negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of
HCG) within 72 hours prior to randomization. This is because of the potential teratogenic
effects of the agents used in this study.
Required Initial Laboratory Values
ANC >= 1,500/[MICRO-SYMBOL]L
Platelet count >= 100,000/[MICRO-SYMBOL]L
Bilirubin <= 1.5 x upper limit of normal
Calculated Creatinine Clearance* >= 60 mL/min
AST/ALT <= 2.5 x upper limit of normal
* Modified Cockroft and Gault formula