Phase III FOLFIRINOX (mFFX) +/- SBRT in Locally Advanced Pancreatic Cancer

A Pancreatic Cancer Radiotherapy Study Group (PanCRS) Trial

Primary Objective:

To determine progression free survival for mFFX +/- SBRT.

Secondary Objectives:

- To determine metastasis free survival following mFFX chemotherapy alone or with SBRT.

- To determine the overall survival in pancreatic cancer patients treated with
chemotherapy +/- SBRT.

- To determine local progression-free survival in pancreatic cancer patients after
chemotherapy +/- SBRT.

- To evaluate acute (within 3 months of treatment) grade 2 or greater gastritis, fistula,
enteritis, or ulcer and any other grade 3-4 gastrointestinal toxicity within 3 months of
treatment.

- To evaluate the utility of FDG-PET for treatment planning and estimation of progression
free survival.

- To identify new biomarkers in pancreatic cancer.

- To evaluate the quality of life of patients before and after either chemotherapy or
chemotherapy and SBRT.

Inclusion Criteria:

- Histologically confirmed adenocarcinoma of the pancreas.

- Induction mFolfirinox up to 4 cycles. Informed consent must be signed by the end of
the second cycle.

- Stable or better disease on re-staging scans.

- Determined unresectable by a pancreatic cancer surgeon or a multi-disciplinary or
gastrointestinal oncology Tumor Board.

- Typically, pancreatic tumors must be less than 8.0 cm in greatest axial dimension at
the time of treatment planning but final determination of eligibility will be based
upon satisfying the radiation normal tissue constraints as per protocol.

- ECOG 0, 1, or 2

- Patients must have acceptable organ and marrow function as defined below and within 30
days of eligibility confirmation:

- leukocytes (WBC) >=3,000/mL

- absolute neutrophil count (ANC)>=1,500mL

- platelets >=50,000/mL

- total bilirubin < or = 1.5 X institutional upper limit of normal

- AST(SGOT)/ALT(SGPT) < or =2.5 X institutional upper limit of normal

- creatinine within normal institutional limits

- Ability to understand and the willingness to sign an informed consent form.

- Life expectancy > 6 months.

Exclusion Criteria:

- Metastatic disease

- Patients who have had prior radiotherapy to the upper abdomen/liver.

- Patients who have received chemotherapy for pancreatic cancer, other than up to 4
cycles of mFolfirinox.

- Children are excluded because pancreatic tumors rarely occur in this age group.
Furthermore, treatment requires a great deal of patient cooperation including the
ability to lie still for several hours in an isolated room.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection (or infections requiring systemic antibiotic treatment), symptomatic
congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric
illness/social situations that would limit compliance with study requirements.

- Any concurrent malignancy other than non-melanoma skin cancer, non-invasive bladder
cancer, or carcinoma in situ of the cervix. Patients with a previous malignancy
without evidence of disease for > 5 years will be allowed to enter the trial.

- Pregnant and breastfeeding women are excluded; as well as women of child-bearing
potential who are unwilling or unable to use an acceptable method of birth control
(hormonal or barrier method of birth control; abstinence) to avoid pregnancy for the
duration of the study. Male subjects must also agree to use effective contraception
for the same period as above. Should a woman become pregnant or suspect she is
pregnant while participating in this study, she should inform her treating physician
immediately.

- Women who are not post-menopausal (as defined in Appendix III) and have a positive
urine or serum pregnancy test or refuse to take a pregnancy test