Biomarker Directed Adjuvant Chemotherapy for Resected Pancreas Cancer
Biomarker Directed Adjuvant Chemotherapy for Resected Pancreas Cancer
Chemotherapy is given after curative surgery for pancreas cancer to try to improve cure
 rates. There are two choices of chemotherapy which are currently considered equal treatments:
 gemcitabine or 5-fluorouracil (5FU). This study is trying to determine if one of two standard
 chemotherapies is better than the other depending on whether patients have high or low human
 equilibrative nucleoside transporter 1 (hENT1). hENT1 is a protein that is found in varying
 amounts on pancreas cancers.
The rationale for this pilot study is based on trying to better deliver adjuvant chemotherapy
 by selecting treatment for patients that is individualized based on the hENT1 biomarker.
 Gemcitabine (gem) requires human equilibrative nucleoside transporter 1 (hENT1) to enter
 cells. If a pancreatic cancer has low hENT1, gem will not be able to enter cells efficiently.
 5-fluorouracil (5FU) does not require the same transport into cells. Thus, upfront hENT1
 testing will allow determination of therapy.
Inclusion Criteria:

 -  Histologically documented pancreatic adenocarcinoma not previously treated with
 systemic therapy.

 -  Complete macroscopic and microscopic (R0) resection for ductal adenocarcinoma of the
 pancreas with no evidence of malignant ascites, peritoneal metastases or distant
 metastases. Lack of recurrent and/metastatic disease must be confirmed radiologically
 with CT chest, abdomen, and pelvis prior to enrolment.

 -  Adequate tissue available for IHC testing of hENT1. Histological/cytological
 confirmation of tissue to ensure sufficient material is available for hENT1 analysis
 by the Cross Cancer Institute (CCI) is required. Paraffin block sufficient for
 preparing ≥ 6 unstained slides for central storage and testing if required by
 oncologist.

 -  ECOG performance status of 0 - 2. (Appendix B)

 -  Age ≥ 18 years

 -  Life expectancy of at least 6 months based on discretion of treating

 -  Adequate hematologic function defined by the following laboratory parameters:
 Hemoglobin > 100, Platelet count > 100 and Absolute granulocyte count > 1.5.

 -  Adequate hepatic and renal function defined by the following laboratory parameters:
 AST and ALT ≤ 2.5 X upper limit of institutional normal, bilirubin ≤ upper limit of
 institutional normal, and calculated creatinine clearance of ≥ 50 mL/min using the
 Cockcroft-Gault formula, if just below 50 mL/min based on this formula then GFR ≥ 50
 mL/min as determined.

 -  Patients may have received prior curative radiotherapy for a different malignancy
 (unless radiation was curative therapy to ≥ 25% of bone marrow stores) and patients
 must have recovered from the toxic effects of this treatment.

 -  Patients must be started on protocol ≤ 10 weeks from the date of curative surgical
 resection, and patients must have recovered from the toxic effects of surgery.

 -  Patients must have the ability to read, understand, and sign an informed consent and
 must be willing to comply with study treatment and follow-up.

 Exclusion Criteria:

 -  Patients who have received prior chemotherapy or radiation delivered as parts of
 initial curative therapy for pancreas cancer (i.e. neoadjuvant or adjuvant
 chemotherapy administered alone and/or concurrently delivered with radiation and/or
 surgery) are not permitted. Metastatic patients are not permitted.

 -  Prior treatment for a different malignancy with > 6 cycles of traditional alkylating
 agent-based chemotherapy, > 2 cycles of carboplatin-based chemotherapy, or concurrent
 treatment with other experimental drugs or anti-cancer therapy.

 -  Lack of physical integrity of the upper gastrointestinal tract, malabsorption
 syndrome, short gut syndrome, or history of bowel obstruction due to peritoneal
 metastases.

 -  Previous or concurrent malignancies, excluding curatively treated in situ carcinoma of
 the cervix or non-melanoma skin cancer, unless at least 5 years have elapsed since
 last treatment and the patient is considered cured.

 -  Any serious medical condition within 6 months prior to study entry such as myocardial
 infarction, uncontrolled congestive heart failure, unstable angina, active
 cardiomyopathy, unstable ventricular arrhythmia, cerebrovascular diseases,
 uncontrolled hypertension, uncontrolled diabetes, uncontrolled psychiatric disorder,
 serious infection, active peptic ulcer disease, or other medical condition that.

 -  Known dihydropyrimidine dehydrogenase (DPD) deficiency.

 -  Pregnant or lactating women; women of child bearing potential must have a negative
 serum pregnancy test within 7 days of trial registration. Women or men of child
 bearing potential must use effective contraception (defined by the treating physician)
 which must be documented in study CRFs.

 -  Any other reason the investigator considers the patient should not participate in the
 study