This is a dose escalation trial to evaluate the safety of stereotactic body radiotherapy (SBRT) delivered in 3 fractions for patients with locally advanced pancreatic cancer (LAPC) who have received induction chemotherapy (FOLFIRINOX or gemcitabine and nab-paclitaxel).
This is a phase I study, with an expansion cohort, of up to 34 patients to identify the maximum tolerated dose (MTD) of a 3-fraction regimen of stereotactic body radiotherapy (SBRT) for locally-advanced pancreatic cancer patients who have not developed distant progression following induction chemotherapy (FOLFIRINOX or gemcitabine and nab-paclitaxel) as per standard of care. After completion of induction chemotherapy, stereotactic body radiotherapy SBRT will be administered in 3 fractions, every other day, on an outpatient basis. Dose escalation will start with dose level 1 (9 Gy x 3 fractions) and increase by 1 Gy per fraction at each dose level, dose level 2 will be 10 Gy x 3 fractions and dose level 3 will be 11 Gy x 3 fractions.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
14
Patients will have received induction chemotherapy for 3+ months with either FOLFIRINOX or gemcitabine/abraxane with at least stable disease.
After completion of induction chemotherapy, stereotactic body radiation therapy (SBRT) will be administered in 3 fractions, every other day, on an outpatient basis. Dose escalation will start with dose level 1 (9 Gy x 3 fractions) and increase by 1 Gy per fraction at each dose level, dose level 2 will be 10 Gy x 3 fractions and dose level 3 will be 11 Gy x 3 fractions.
University of Colorado
Aurora, Colorado, United States
The Maximum Tolerated Dose (MTD) of Stereotactic Body Radiotherapy (SBRT) in Locally Advanced Pancreatic Cancer (LAPC) Patients Who Have Not Developed Distant Progression After Induction Chemotherapies.
This will be accomplished by the standard 3+3 dose escalation design. Dose limiting toxicities (DLT) are defined by ≥ Grade 3 treatment-related GI toxicity within 3 months of SBRT. These include: (1) Bowel (includes bowel perforation, obstruction, or hemorrhage) and (2) Stomach (bleeding ulcer, perforation) as determined by imaging or endoscopic evaluation.
Time frame: Up to 3 months
Local Control
Local control (LC) will be measured from completion of SBRT to the time of identification of any local progression by imaging or surgical exploration. The pattern of patients experiencing local, distant or local with distant failure will be estimated using competing risks method.
Time frame: Up to 5 years
Progression Free Survival
Progression free survival (PFS) will be measured from completion of SBRT to the time of tumor progression or death due to any cause. PFS will be estimated using the method of Kaplan and Meier.
Time frame: Up to 5 years
Overall Survival
Overall survival (OS) will be measured from completion of SBRT until death due to any cause. OS will be estimated using the method of Kaplan and Meier.
Time frame: Up to 5 years
Small Intestine Changes
Investigators will measure changes in the perfusion/permeability related parameters of peripancreatic small intestine before, during and after SBRT for patients using pCT and correlating these changes with the development of gastrointestinal toxicity such as duodenal ulcers, strictures, or enteritis. Patients will undergo baseline, post-first-fraction SBRT and post-treatment CT scans.
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Time frame: 6 weeks after SBRT
Vascular and Cellular Changes
Investigators will measure changes in diffusion and perfusion/permeability by using perfusion CT derived parameters that can predict treatment response and to assess any correlation between these perfusion CT derived parameters and local control and progression-free survival
Time frame: 6 weeks after SBRT
Quality of Life (QOL)
The primary objective of the QOL study is to document the patient's experience of treatment for locally advanced pancreatic cancer by examining global QOL, physical symptoms, physical functioning and emotional well-being at baseline, during treatment, and after treatment. QOL measures including EORTC-QLQ-C30 questionnaire and the Pancreatic Cancer subscale (EORTC-PAN26) will be assessed 14 days prior to SBRT (Time 0), 10-12 weeks after SBRT (Time 1), and 6 months after SBRT (Time 2). The primary QOL endpoints include the EORTC global QOL, physical symptoms, physical functioning and emotional well-being.
Time frame: 6 months after SBRT