Adaptive Modification of Neoadjuvant Therapy Based on Clinical Response in Patients With Localized Pancreatic Cancer

Patients will receive standard chemotherapy and chemoradiation for pancreatic cancer. The
study intervention is an adaptive approach which modifies systemic therapy based on clinical
assessments of treatment response. Treatment response will be assessed by imaging (CT scan),
biomarker (serum CA19-9) and performance status assessment (SPPB and CES-D evaluations) at
the first restaging assessment.

Treatment response will be categorized as:

1. response;

2. stable disease;

3. local disease progression;

4. metastatic disease progression.

After the first restaging evaluation, patients who demonstrate:

1. a response will be maintained on the same chemotherapy;

2. stable disease will be changed to a defined alternative chemotherapy or molecular
profile-directed therapy;

3. local progression will receive chemoradiation;

4. metastatic disease will be removed from the trial.

Patients who complete four months of chemotherapy, will be treated with chemoradiation
(50.4Gy in 28 fractions). In the absence of local disease progression deemed inoperable, or
metastatic disease progression, patients will be offered surgical resection. Patients who did
not receive four months of systemic therapy in the neoadjuvant setting will be offered four
months of adjuvant therapy at the discretion of their treating physicians.

INCLUSION CRITERIA

- Be 18 years of age or older.

- Be able to understand and provide written informed consent or have a legally
authorized representative (LAR).

- Have an ECOG performance status < 2 (please see the appendix).

- Have documentation of histologically confirmed adenocarcinoma. Biopsy must have been
completed prior to start of treatment; additional biopsy is not required for the
study.

- Have clinical stage consistent with resectable or borderline resectable adenocarcinoma
of the pancreas, based on CT or MRI findings.

- Have adequate organ and bone marrow function, as defined by:

- total leukocytes >3 x103/μL.

- absolute neutrophil count (ANC) >1.5x 103/μL.

- hemoglobin >9 g/dL.

- platelets >100 x 10e3/μL.

- creatinine clearance >60 mL/min or creatinine <1.5 mg/dL; bilirubin < 2 mg/dL.

- aspartate transaminases (AST/SGOT) <3 x ULN.

- alanine transaminases (ALT/SGPT) <3 x ULN.

- Subjects must be CA19-9 producers as defined by a pretreatment CA 19-9 > 35 U/mL, when
total bilirubin <2 mg/dL.

- Female patients must be postmenopausal (absence of menses for > 1 year), surgically
sterile, or have a negative pregnancy test and use at least one form of contraception
for four weeks prior to Day 1 of the study, during study treatment and during the
first four months after study treatment is discontinued. Male patients must be
surgically sterile or use barrier contraception during the study and for four months
after the last dose of any study drug.

EXCLUSION CRITERIA

- Has received chemotherapy and/or radiation within three years prior to study
enrollment.

- Has any previous history of another malignancy (other than cured basal or squamous
cell carcinoma of the skin or cured in situ carcinoma of the cervix or localized
prostate cancer with normal prostate specific antigen) within three years of study
enrollment.

- Uncontrolled comorbidities including, but not limited to, ongoing or active serious
infection, symptomatic congestive heart failure, unstable angina, unstable cardiac
arrhythmias, psychiatric illness, excessive obesity (BMI >55) or situations that would
limit compliance with the study requirements or the ability to willingly give written
informed consent.

- Known HIV, HBV or HCV infection.

- Pregnant or breastfeeding patients or any patient with childbearing potential not
using contraception four weeks prior to treatment.