This phase II trial studies how well the combination of chemotherapy drugs called FOLFIRINOX (levoleucovorin or leucovorin, 5-fluorouracil, irinotecan and oxaliplatin) followed by stereotactic body radiation therapy works in treating patients with pancreatic cancer that has not spread to other places in the body (non-metastatic) and cannot be removed by surgery (unresectable). Chemotherapy drugs, such as levoleucovorin or leucovorin, 5-fluorouracil, irinotecan, 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 is a radiation therapy approach which delivers high dose radiation to a tumor in the body in a single treatment session or up to 5 treatment sessions (one dose per day). Giving chemotherapy with stereotactic body radiation therapy may kill more tumor cells.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03991962.
PRIMARY OBJECTIVE:
I. To evaluate progression free survival after modified FOLFIRINOX and subsequent stereotactic body radiation therapy (SBRT) in borderline resectable and locally advanced pancreatic cancer.
SECONDARY OBJECTIVES:
I. To evaluate the radiographic response to FOLFIRINOX and SBRT by comparing intravenous (IV) contrast computed tomography (CT) scans before and after therapy.
II. To determine rates of recurrence (local only, systemic only, and both local and systemic), and overall survival.
III. 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 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, and before and after radiation) as a predictor of outcomes.
III. To correlate response of CA19-9 to chemotherapy and SBRT 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 FOLFIRINOX (at the time of fiducial placement for SBRT), and after SBRT (at the time of response assessment EUS) for future correlative biomarker studies.
OUTLINE:
Patients receive oxaliplatin IV over 2 hours, leucovorin calcium or levoleucovorin calcium over 2 hours, irinotecan hydrochloride IV over 90 minutes and fluorouracil IV over 15 minutes then continuously over 46 hours on day 1. Treatment repeats every 14 days for up to 6-12 cycles in the absence of disease progression or unacceptable toxicity. Within 4 weeks of chemotherapy completion, patients without evidence of distant progression undergo 5 fractions of SBRT over 2-3 weeks. Patients also undergo CT or magnetic resonance imaging (MRI), EUS, core biopsy, and blood sample collection throughout the study.
After completion of study treatment, patients are followed up every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter.
Lead OrganizationYale University
Principal InvestigatorKimberly Lauren Johung
