Neoadjuvant FOLFIRINOX and Chemoradiation Followed by Definitive Surgery and Postoperative Gemcitabine for Patients With Borderline Resectable Pancreatic Adenocarcinoma: An Intergroup Single-Arm Pilot Study

Inclusion Criteria

Pre-Registration Eligibility Criteria

- Documentation of Disease and Radiographic Staging

- Cytologic or histologic proof of adenocarcinoma of the pancreatic head or
uncinate process

- Objective radiographic staging with a) contrast-enhanced, helical thin-cut
computed tomography (CT)/magnetic resonance imaging (MRI) scan of the abdomen
and b) CT scan/MRI of the chest

- Note: echoendoscopic staging will be permitted as an adjunctive modality, but
all stage definitions below will be determined using CT/MRI as outlined below.
In the event echoendoscopic stage and CT/MRI stage are discordant, the CT/MRI
stage will be used. Significant discordance should be discussed with the study
principal investigator (PI) prior to enrollment


- Borderline resectable primary tumor, defined by the presence of any one or more
of the following on CT/MRI, and confirmed by central radiographic review:

- An interface between the primary tumor and the superior mesenteric vein or
portal vein (SMV-PV) measuring ≥ 180 degrees of the circumference of the
vessel wall


- Short-segment occlusion of the SMV-PV with normal vein above and below the
level of obstruction that is amenable to resection and venous
reconstruction

- Short segment interface (of any degree) between tumor and hepatic artery
with normal artery proximal and distal to the interface that is amenable to
resection and reconstruction


- An interface between the tumor and superior mesenteric artery (SMA)
measuring < 180 degrees of the circumference of the vessel wall

- No potentially resectable disease defined as primary tumors with all of the
following: 


- An interface between the primary tumor and the superior mesenteric vein or
portal vein (SMV-PV) measuring < 180 degrees of the circumference of the
vessel wall


- No radiographic interface between the tumor and the (superior mesenteric
artery) SMA, hepatic artery or celiac axis


- No radiographic evidence of metastatic disease

- No metastatic disease defined as any one or more of the following:

- Suspicious lymphadenopathy outside the standard surgical field (i.e.,
aortocaval nodes, distant abdominal nodes)


- Radiographic evidence for metastatic disease in distant organs, such as
masses in distant organs or ascites

- No locally advanced and/or unresectable disease clearly defined by any one or
more of the following by CT/MRI:


- An interface between the tumor and the SMA measuring ≥ 180 degrees of the
circumference of the vessel wall


- No interface between the tumor and the aorta


- Occlusion of the SMV or portal vein without a sufficient cuff of normal
vein above and below the level of obstruction with which to perform venous
reconstruction


- Long-segment interface (of any degree) between the tumor and the common
hepatic artery or its major tributaries with insufficient artery proximal
and distal to the interface to perform reconstruction

- No prior chemotherapy or chemoradiation for pancreatic cancer

- No patients with a "currently active" second malignancy other than non-melanoma skin
cancers. Patients are not considered to have a "currently active" malignancy if they
have completed therapy and are free of disease for ≥ 3 years

- Baseline peripheral sensory neuropathy must be grade < 2

- No patients with known Gilbert's Syndrome or homozygosity for UGT1A1*28 polymorphism

- No history of pulmonary embolism in the past 6 months

- Age ≥ 18 years of age

- Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status 0-1

- Pregnancy/Nursing Status: Non-pregnant and non-breast-feeding. Female participants of
child-bearing potential must have a negative urine or serum pregnancy test prior to
registration. Perimenopausal participants must be amenorrheic > 12 months to be
considered not of childbearing potential.

- Required Pre-Registration Laboratory Values:

- Granulocytes ≥ 2,000/ul

- Hemoglobin > 9 g/dL

- Platelets ≥ 100,000/ul

- Albumin > 3.0 g/dL

- Creatinine ≤1.5 x upper limit of normal (ULN)

- Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase [SGOT]
& alanine aminotransferase (ALT) serum glutamate pyruvate transaminase [SGPT]) ≤
2.5 x ULN

Registration Eligibility Criteria

- Confirmation of pre-registration eligibility criteria as described under
"Documentation of Disease and Radiographic Staging" by the Alliance Central
Radiographic Review

- Required Registration Laboratory Values:

- Bilirubin ≤ 2 mg/dl

- Cancer antigen (CA)19-9 < 1000 U/ml (from time point when bilirubin is ≤ 2
mg/dl)