Span-C-SBRT for Pancreatic Cancer

Study Overview
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Brief Summary
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To assess the freedom from local failure at 12 months after Stereotactic Body Radiotherapy (SBRT). Also to assess the safety, efficacy and feasibility of SBRT in the treatment of high risk localised pancreatic cancer.

Detailed Description
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Patients must have histologically or cytologically confirmed high risk localised adenocarcinoma of the pancreas, including patients with extrapancreatic extension (Stage IIA), node positive (Stage IIB), borderline resectable or locally advanced pancreatic cancer as defined by Australasian Gastro-Intestinal Trials Group (AGITG) guidelines. ECOG performance status 0-1, suitable for chemotherapy and radiotherapy. After a minimum of 2 months of neoadjuvant chemotherapy using either an oxaliplatin- based regimen (FOLFOX, FOLFIRINOX, mFOLFIRINOX)+/- immunotherapy/molecular agent or gemcitabine based chemotherapy (eg gemcitabine / gemcitabine/abraxane). Participants will receive SBRT (30-45Gray in 5 fractions over 2 weeks. Prior to SBRT, fiducial markers will be placed to aid with image guidance during radiation delivery. Four weeks after completion of SBRT participants will have re-staging using positron emission tomography (PET) and computed tomography (CT) scan. Participants will be discussed in the multidisciplinary team meeting for consideration of surgery. Those considered to be resectable will proceed to have surgery 6-10 weeks post SBRT.

Official Title
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Stereotactic Body Radiotherapy [SBRT] for High Risk Localised Pancreatic Cancer: a Phase II Study of the Department of Radiation Oncology Royal North Shore Hospital (Span-C - SBRT for Pancreatic Cancer)

Conditions
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High Risk Localised Pancreatic Cancer

Intervention / Treatment
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* Radiation: Stereotactic Body Radiotherapy (SBRT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 and able to give informed consent Patients with histologically or cytologically confirmed locally advanced adenocarcinoma of the pancreas, including patients with extrapancreatic extension (Stage IIA), node positive (Stage IIB), borderline resectable or locally advanced as defined by AGITG guidelines ECOG performance status 0-1 Measurable disease as defined by RECIST 1.1 Have received or plan to receive chemotherapy Successful insertion of fiducial markers Exclusion Criteria: Patients with metastatic pancreas cancer Prior abdominal radiotherapy Active malignancy excluding non melanomatous skin cancer Neuroendocrine pancreatic carcinoma Pregnant or lactating women Tumour size greater then 70mm Age >85

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 86 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: non randomised-single arm phase II
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stereotactic Body Radiotherapy (SBRT)<br>Prior to SBRT, fiducial markers will be placed to aid with image guidance during radiation delivery. Fiducials will be inserted endoscopically (preferable) or intraoperatively. After this procedure, patients will have radiotherapy planning. During treatment, the fiducials will be used for registration with the images acquired during treatment (including kV fluoroscopy, MV or optical). The acquired images may be processed to determine fiducial location using KIM or MATT software from University of Sydney. SBRT 30-45Gray in 5 fractions will be given over 2 weeks. Four weeks after completion of SBRT participants will repeat a re-staging PET and CT scans. Those considered to be resectable will proceed to have surgery 6-10 weeks post SBRT. | Radiation: Stereotactic Body Radiotherapy (SBRT)<br>* Stereotactic Body Radiotherapy (SBRT) 30-45 gray in 5 fractions over 2 weeks will be given to all eligible patients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| freedom of local failure | patient who do no have local failure | 12 months from end of radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of SBRT treatment related adverse events in this group of patients | assess acute and late radiotherapy toxicity using CTCAE version 4.3, to compare toxicity with conventional treatment | Acute toxicity-from start of SBRT up to 3 months after SBRT. Late RT toxicity: from 3 months to 2 years after SBRT. | 
| Response to neoadjuvant treatments | Determine by pathology and radiological response rates after neoadjuvant treatment, | from date of surgery through to 24 months post surgery | 
| Feasibility of internal-external correlation model (MATT) | Determine the feasibility of the University of Sydney internal-external correlation model (MATT) to determine pancreas motion. Feasibility is determined as predicted motion with MATT is within 2mm of actual motion measured with fluoroscopic x-rays of fiducial markers during treatment. | during SBRT radiotherapy treatment | 
| Surgical complications | To assess surgical complications | 30 to 90 days post surgery | 
| Duration of hospital admission after surgery | to assess extended stay in the hospital after surgery | from date of surgery through study completion (ie 24 months) | 
| margin negative (R0) resection rate | to assess margin negative resection rate (i.e. response to treatment) | through study completion, average of 2 years | 
| median overall survival (OS) | To assess median overall survival after treatment | 12 months after treatment | 
| progression free survival (PFS) | To assess the PFS rate after treatment | 12 months after treatment | 
| Feasibility of Using Kilovoltage Intra-fraction Monitoring (KIM) to determine pancreas motion | Determine the feasibility of the University of Sydney Kilovoltage Intra-fraction Monitoring (KIM) software to determine pancreas motion. Feasibility is determined as predicted motion with KIM is within 2mm of actual motion measured with fluoroscopic x-rays of fiducial markers during treatment. | during SBRT radiotherapy treatment |