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Patients undergo hypofractionated stereotactic body radiation therapy in 5 fractions on days 1-5. Patients receive fluorouracil IV over 24 hours on day 1 weekly for 4 weeks or capecitabine PO every 12 hours starting the evening before day 1 of radiation therapy for 4 weeks as per standard of care. Patients then undergo surgery 6-8 weeks after completion of radiation therapy.

Patients receive zoledronic acid IV over no less than 15 minutes 1 week prior to radiation therapy. Patients undergo hypofractionated stereotactic body radiation therapy and receive treatment with fluorouracil IV or capecitabine PO as in Arm A. Patients then undergo surgery 6-8 weeks after completion of radiation therapy.

Laboratory Biomarker Analysis

Pharmacological Study

Undergo hypofractionated stereotactic radiotherapy

Stereotactic Body Radiation Therapy

Chi Lin, MD, PhD

This randomized phase II trial studies how well hypofractionated stereotactic body radiation therapy and fluorouracil or capecitabine with or without zoledronic acid work in treating patients with pancreatic cancer that has spread from where it started to nearby tissue or lymph nodes. Hypofractionated stereotactic body radiation therapy is a specialized radiation therapy that sends higher doses of x-rays over a shorter period of time directly to the tumor using smaller doses over several days and may cause less damage to normal tissue. Drugs used in chemotherapy, such as fluorouracil and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Zoledronic acid is used in cancer patients to reduce cancer symptoms and may make tumor cells more sensitive to radiation. Giving hypofractionated stereotactic body radiation therapy and fluorouracil or capecitabine with or without zoledronic acid may work better in treating patients with pancreatic cancer.

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of hypofractionated radiation therapy concurrently with zoledronic acid (Zometa) and fluorouracil (5Fu) or capecitabine.

SECONDARY OBJECTIVES:

I. To examine the toxicity of Zometa while it is used concurrently with hypofractionated radiation therapy.

II. To evaluate local failure-free survival and overall survival, surgical resection rate and tumor response rate.

TERTIARY OBJECTIVES:

I. To quantify the amplitude of the expression of genes that are involved in cholesterol biosynthesis (ACAT2, DHCR7, ELFN2, FASN, SC4MOL, and SQLE) in pancreatic tumor tissue prior to and following the Zometa and radiation therapy if the pancreatic cancer tissue is available.

II. To measure Zometa pharmacokinetics at steady-state. III. To evaluate tumor and organ motion with 4 dimension(D) computed tomography (CT) and respiratory gating system and to evaluate the effect of tumor/organ motion on the dosimetry, local control and survival.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients undergo hypofractionated stereotactic body radiation therapy in 5 fractions on days 1-5. Patients receive fluorouracil intravenously (IV) over 24 hours on day 1 weekly for 4 weeks or capecitabine orally (PO) every 12 hours starting the evening before day 1 of radiation therapy for 4 weeks as per standard of care. Patients then undergo surgery 6-8 weeks after completion of radiation therapy.

ARM B: Patients receive zoledronic acid IV over no less than 15 minutes 1 week prior to radiation therapy. Patients undergo hypofractionated stereotactic body radiation therapy and receive treatment with fluorouracil IV or capecitabine PO as in Arm A. Patients then undergo surgery 6-8 weeks after completion of radiation therapy.

After completion of study treatment, patients are followed up for 30 days, every 3 months for the first year, every 4 months for the second year, and then every 6 months thereafter.

Hypofractionated Stereotactic Body Radiation & Fluorouracil or Capecitabine for Locally Advanced Pancreatic Cancer

A Randomized Phase II Study of the Efficacy and Safety of Hypofractionated Stereotactic Radiotherapy and 5FU or Capecitabine With and Without Zometa in Patients With Locally Advanced Pancreatic Adenocarcinoma

Change in expression of genes involved in cholesterol biosynthesis in patients who undergo resection will be assessed.

The concentration of plasma zoledronic acid will be measured.in patients who received zoledronic acid

Safety variables to be analyzed are adverse events. Adverse events will be tallied for overall frequency (number and percentage of subjects), worst reported severity, and relationship to study drugs. Serious adverse events will be summarized similarly.

Time to local failure will be analyzed using Kaplan-Meier method

Time to death will be analyzed using Kaplan-Meier method

The number and proportion of patients undergoing complete resection will be reported.

The pathologic response will be scored from 0-9 by a pathologist, 0 is no response and 9 is complete response.

The size of tumor will be measured on CT/MRI before and after SBRT

The max and average SUV will be measured on PET before and after SBRT

The amplitude of 3D tumor/organ motion will be measured using 4D CT scans

Spots Global Cancer Trial Database for stage ib pancreatic cancer ajcc v6 and v7