Phase I Study of Stereotactic Body Radiation Therapy and FOLFIRINOX in the Neoadjuvant Therapy of Pancreatic Cancer

The current standard of care for treating early stage pancreatic cancer involves surgery
followed by chemotherapy and / or chemoradiotherapy using conventional fractionated external
beam radiation therapy (EBRT). Despite the the incorporation of multi-modality adjuvant
therapy following surgery, patients with surgically resected pancreas cancer have a high
likelihood of recurrence of their cancer and/ or death from their disease. Patients with
more advanced pancreatic cancers experience even worse outcomes in the face of unresectable
disease or lower likelihood of achieving a negative margin resection. In these particular
group of patients, chemotherapy and radiation given prior to surgery may help select
patients who are more likely ultimately to benefit from a pancreaticoduodenectomy and may
improve the rate of margin negative resection, factors which may influence their outcome.

Systemic chemotherapy traditionally used in the treatment of pancreatic cancer has included
drugs such as gemcitabine or 5-fluorouracil (5-FU). Recently, a multi-agent chemotherapy
regimen called FOLFIRINOX has shown significant efficacy in patients with advanced
pancreatic cancer with improved tumor responses and improved overall outcomes with a
reasonable toxicity profile.

Stereotactic body radiotherapy (SBRT) is a unique radiation technique that allows higher
doses of radiation to be delivered to the cancer over a significantly shorter period of time
compared to conventional radiation. SBRT's advantages over conventional radiation include:
shorter duration of therapy (one to three days versus two to five weeks) as well as the
ability to deliver full doses of chemotherapy. In treating patients with pancreatic cancer,
SBRT has been tolerated and has been effective when compared historically to conventional
radiation. SBRT has been combined with chemotherapy and has also been very well tolerated in
patients with pancreatic cancer.

This study will ask whether giving chemotherapy with FOLFIRINOX followed in short sequence
by radiation therapy using Stereotactic Body Radiation Therapy (SBRT) is safe and feasible.
This study will also begin to ask what is the effect of this approach on the rate of margin
negative resection in patients who may subsequently undergo surgery for their pancreatic
cancer.

Inclusion Criteria: Patients eligible must have:

- Histologic or cytologic diagnosis of pancreatic adenocarcinoma.

- Radiographically resectable or borderline resectable disease as reviewed by an
experienced surgical oncologist at Emory.

- Age 21 years or older.

- Not received prior chemotherapy or radiation for pancreatic cancer.

- ECOG performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG)
scale.

- Adequate bone marrow function: absolute neutrophil count > 1,500/cmm, platelet count
> 100,000/cmm.

- Understanding and be informed of the investigational nature of this study and must
give written informed consent prior to the receiving of treatment per this protocol.

Exclusion Criteria: Patients who are not eligible have

- Histologies including endocrine tumors or lymphoma of the pancreas.

- A tumor which is less than 3 mm from the duodenum as measured by either CT or MRI.

- History of central nervous system (CNS) metastases.

- Liver dysfunction, including total bilirubin > 1.5 mg/dL; aspartate transaminase
(AST) and alanine amino transferase (ALT) > 5 times upper limit of the institutional
normal.

- Creatinine ≥ 1.5 mg/dL.

- Albumin ≤ 2.5 g/dL.

- International Normalized Ratio (INR) ≥ 1.5 (in the absence of ongoing treatment with
warfarin).

- Breast feeding.

- Serious active infection.

- Serious concurrent systemic disorders incompatible with participating in the study
(at the discretion of the investigator).

- An active second primary malignancy (except in situ carcinoma of the cervix, or
adequately treated basal cell carcinoma of the skin) within less than one year of
enrollment into this study.

- Clinical evidence of distant metastatic disease.