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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: mFOLFIRINOX; Radiation: Stereotactic body radiotherapy (SBRT)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mFOLFIRINOX followed by SBRT; Patients will receive mFOLFIRINOX, followed stereotactic body radiotherapy (SBRT).	Drug: mFOLFIRINOX; Patients will receive 6-12 cycles of mFOLFIRINOX every 2 weeks; Radiation: Stereotactic body radiotherapy (SBRT); 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Kimberly Johung, MD, PhD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2019
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: June 18, 2019
• First Submitted That Met QC Criteria: June 18, 2019
• First Posted (Actual): June 19, 2019

Study Record Updates

• Last Update Posted (Estimated): December 24, 2025
• Last Update Submitted That Met QC Criteria: December 22, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Radiosurgery
• Other Study ID Numbers: 2000024671

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes