Phase II Study to Evaluate Modified Folfirinox and Stereotactic Body Radiation Therapy in Non-metastatic Unresectable Pancreatic Adenocarcinoma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of modified FOLFIRINOX followed by stereotactic body radiotherapy (SBRT) in patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC). The primary hypothesis will be to determine if modified FOLFIRINOX followed by SBRT improves progression free survival (PFS) compared to historical controls treated with gemcitabine-based chemotherapy with or without standard fractionated radiation.

Detailed Description
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The Primary and Secondary are listed below. Primary Objective: - To evaluate progression free survival after modified FOLFIRINOX and SBRT in borderline resectable and locally advanced pancreatic cancer. Secondary Objective: To evaluate the radiographic response to FOLFIRINOX and SBRT by comparing IV contrast CT scans before and after therapy. To determine rates of recurrence (local only, systemic only, and both local and systemic), and overall survival. 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.

Official Title
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Phase II Study to Evaluate Modified Folfirinox and Stereotactic Body Radiation Therapy in Non-metastatic Unresectable Pancreatic Adenocarcinoma

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: mFOLFIRINOX
* Radiation: Stereotactic body radiotherapy (SBRT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed pancreatic adenocarcinoma Borderline resectable pancreatic adenocarcinoma or locally advanced pancreatic adenocarcinoma No evidence of extrapancreatic disease on diagnostic imaging No evidence of invasion into the duodenum or stomach, as determined by EGD/EUS No prior treatment (chemotherapy, biological therapy, or radiotherapy) for pancreatic cancer No prior treatment with oxaliplatin, irinotecan, fluorouracil, or capecitabine ECOG Performance Status of 0-1 No other malignancy within past five years (exceptions include basal cell carcinoma of the skin, cervical carcinoma in situ, and non-metastatic prostate cancer) No evidence of second malignancy at the time of study entry No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung No > grade 2 sensory peripheral neuropathy No uncontrolled seizure disorder, active neurological disease, or known CNS disease No significant cardiac disease, including the following: unstable angina, New York Heart Association class II-IV congestive heart failure, myocardial infarction within six months prior to study enrollment Not pregnant and not nursing No other medical condition or reason that, in the opinion of the investigator, would preclude study participation Laboratory parameters as follows: Absolute neutrophil count ≥1,500/uL, Platelet count ≥75,000/uL, Hemoglobin ≥9 g,/dL, Creatinine <1.5 X ULN or estimated GFR >30 ml/min, Bilirubin <1.5 X ULN, AST and ALT <3 X ULN, Negative pregnancy test in women of childbearing potential Able to be treated with SBRT only at the Smilow New Haven campus Able to have fiducials placed in the pancreas Exclusion Criteria: Failing to meet any of the Inclusion Criteria

Ages Eligible for Study
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Minimum Age: 18 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: Open label, single group design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mFOLFIRINOX followed by SBRT<br>Patients will receive mFOLFIRINOX, followed stereotactic body radiotherapy (SBRT). | Drug: mFOLFIRINOX<br>* Patients will receive 6-12 cycles of mFOLFIRINOX every 2 weeks<br>Radiation: Stereotactic body radiotherapy (SBRT)<br>* Stereotactic body radiotherapy (SBRT) will be delivered to the primary tumor and any adjacent involved lymph nodes to 33 Gy in 5 fractions over the course of 2 weeks, and within 4 weeks of chemotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Progression-free survival (PFS) at will be judged by CT scan and Response evaluation criteria in solid tumors (RECIST). | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic Response | Radiographic response to FOLFIRINOX and SBRT will be done by comparing IV contrast CT scans before and after therapy. | Within 21 days of starting study drug | 
| Rates of Recurrence | Rates of recurrence (local only, systemic only, and both local and systemic) will be monitored for up to 3 years depending on time when the initiation of treatment begins. | Up to 3 years | 
| Rates of grade 3 or greater gastrointestinal toxicity | Grade 3 or greater gastrointestinal toxicities will be monitored including acute toxicities occurring within 3 months of treatment, and late toxicities occurring over 3 months after completion of radiation. | Up to 3 months post treatment | 
| Overall Survival | Patients will be monitored for overall survival for up to 3 years depending on time when the initiation of treatment begins. | Up to 3 years |