This phase II trial studies how well combination chemotherapy and stereotactic body radiation therapy work in treating patients with pancreatic cancer that can be removed by surgery. Drugs used in chemotherapy, such as fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin, 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. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving combination chemotherapy followed by stereotactic body radiation therapy may work better in treating patients with pancreatic cancer.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03099265.
PRIMARY OBJECTIVES:
I. To evaluate the residual tumor (R0) resection rate after neoadjuvant modified fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin (FOLFIRINOX) and subsequent stereotactic body radiation therapy (SBRT) for borderline resectable pancreatic cancer.
SECONDARY OBJECTIVES:
I. To evaluate the radiographic response to neoadjuvant therapy by comparing intravenous (IV) contrast computed tomography (CT) scans before and after therapy.
II. To evaluate the pathologic response to neoadjuvant chemotherapy and stereotactic radiation.
III. To determine rates of recurrence (local only, systemic only, and both local and systemic), progression free survival, and overall survival.
IV. To determine rates of grade 3 or greater gastrointestinal toxicity, including acute toxicities occurring within 3 months of treatment, and late toxicities occurring over 3 months after completion of radiation.
EXPLORATORY OBJECTIVES:
I. To prospectively assess quantitative KRAS mutation-associated circulating tumor deoxyribonucleic acid (DNA) as a predictive marker of response to neoadjuvant therapy or a prognostic marker of outcomes.
II. To evaluate endoscopic ultrasound elastography measurements of tumor stiffness (change in strain ratio between the normal and tumor region before and after chemotherapy) as a predictor of outcomes.
III. To correlate response of CA19-9 to pre-operative therapy with outcomes.
IV. To collect and bank serial serum and plasma specimens from subjects for future correlative biomarker studies.
V. To collect and bank tumor tissue from subjects prior to treatment (at the time of diagnostic endoscopic ultrasound [EUS]), after treatment with pre-operative FOLFIRINOX (at the time of fiducial placement for SBRT), and after SBRT (from the surgical specimen) for future correlative biomarker studies
OUTLINE:
Patients receive mFOLFIRINOX consisting of oxaliplatin IV over 2 hours, leucovorin calcium or levoleucovorin IV over 2 hours, irinotecan IV over 90 minutes, and fluorouracil IV continuous over 46 hours on day 1. Courses repeat every 14 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients without progression receive 5 fractions of stereotactic body radiation therapy over 2 weeks and undergo surgical resection within 4-12 weeks of completing SBRT. Within 12 weeks after surgery, patients receive mFOLFIRINOX for an additional 4 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter.
Lead OrganizationYale University
Principal InvestigatorKimberly Lauren Johung
