Neoadjuvant Modified FOLFIRINOX and Stereotactic Body Radiation Therapy in Borderline Resectable Pancreatic Adenocarcinoma

Phase II Study to Evaluate Neoadjuvant Modified FOLFIRINOX and Stereotactic Body Radiation Therapy in Borderline Resectable Pancreatic Adenocarcinoma

Surgical resection is the only potentially curative treatment for patients with pancreatic cancer. Patients with BRPC have tumors in close contact with the vasculature but not to the extent that resection is prohibited. Nonetheless, retrospective studies have shown that immediate resection in these patients is associated with an increased risk of positive margins, and a margin positive resection does not improve survival over that of patients with unresectable disease. Moreover, even in those patients where a successful resection is achieved, there is a high rate of early metastatic progression suggesting that micrometastatic disease is often present at diagnosis. Therefore neoadjuvant therapy is likely to improve outcomes in patients with BRPC to increase the likelihood of achieving a margin negative resection, provide early control of occult micrometastatic disease, and select those patients without systemic progression who would benefit from surgical resection.

Study Overview

• Status: Terminated
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: neoadjuvant mFOLFIRINOX; Drug: Stereotactic body radiotherapy (SBRT)

Detailed Description

Given the superior outcomes with FOLFIRINOX and the potential for improved local response with SBRT, the investigators propose to evaluate the efficacy of pre-operative modified FOLFIRINOX followed by SBRT in patients with borderline resectable pancreatic adenocarcinoma. The investigators hypothesize that pre-operative modified FOLFIRINOX followed by SBRT will improve the rate of R0 resections compared to historical controls treated with standard gemcitabine-based chemotherapy and fractionated radiation prior to surgery.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Smilow Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed pancreatic adenocarcinoma
• Borderline resectable pancreatic adenocarcinoma, determined centrally by review of a diagnostic CT scan and/or MRI scan with contrast by a dedicated surgical oncologist and radiologist, or as determined by EUS, and defined according to the NCCN consensus guidelines
• ECOG Performance Status of 0-1
• Age > 18

• Laboratory parameters as follows:

  • Absolute neutrophil count >=1,500/uL
  • Platelet count >=100,000/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 have fiducials placed in the pancreas
• Patients who received chemotherapy >5 years ago for malignancies other than pancreatic cancer are eligible

Exclusion Criteria:

• Evidence of extrapancreatic disease on diagnostic imaging (CT, MRI, or PET scan), or laparoscopy, including nodal involvement beyond the peripancreatic tissues and/or distant metastases
• Evidence of invasion into the duodenum or stomach, as determined by EGD/EUS
• Prior treatment (chemotherapy, biological therapy, or radiotherapy) for pancreatic cancer
• Prior treatment with oxaliplatin, irinotecan, fluoruouracil or capecitabine
• Major surgery within 4 weeks of study entry
• Other concurrent anticancer therapies
• Other malignancy within the past five years (exceptions include basal cell carcinoma of the skin, cervical carcinoma in situ, and non-metastatic prostate cancer)
• Evidence of second malignancy at the time of study entry
• Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
• Grade 2 or greater sensory peripheral neuropathy
• Uncontrolled seizure disorder, active neurological disease, or known CNS disease
• 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
• Pregnant or nursing
• Other medical condition or reason that, in the opinion of the investigator, would preclude study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: patients with borderline resectable pancreatic adenocarcinoma; Borderline resectable disease will be defined by NCCN criteria, and determined centrally by review of a diagnostic pancreas protocol CT scan and/or MRI scan with contrast by a dedicated surgical oncologist and radiologist.

Drug: neoadjuvant mFOLFIRINOX; Patients will receive 8 cycles of mFOLFIRINOX every 2 weeks. mFOLFIRINOX will be dosed as follows: Oxaliplatin 85 mg/m2, followed by folinic acid 400 mg/m2 infused over 120 minutes and irinotecan 135 mg/m2 infused over 90 minutes, followed by 5-fluorouracil 300 mg/m2 IV bolus, followed by 2,400 mg/m2 continuous infusion for 46 hours. Levoleucovorin may be substituted for folinic acid at a dose of 200 mg/m2 infused over 120 minutes.; Other Names: 5-fluorouracil; Leucovorin; folinic acid; Irinotecan; Oxaliplatin; Drug: Stereotactic body radiotherapy (SBRT); Stereotactic body radiotherapy (SBRT) will be delivered to the primary tumor and any adjacent involved 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
Number of Participants With and Without R0 Resection	The primary outcome of this study is the R0 resection count of patients with BRPC treated with neoadjuvant mFOLFIRINOX and SBRT. R0 resection indicates a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed. When the study results were entered, rate was replaced with count as the manner in which these data were summarized.	Up to 40 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Response to Neoadjuvant Therapy Using RECIST	Response to treatment will be assessed by the treating physicians and investigators according to RECIST version 1.1. Counts of participants' RECIST category at their final visit up to 40 weeks below are provided. Per Response Evaluation Criteria In Solid TumorsCriteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response(CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	Up to 40 weeks
Number of Participants With and Without Pathologic Response to Neoadjuvant Therapy	A pathologic complete response is defined as the absence of residual invasive disease at the completion of the neoadjuvant treatment. This was performed only in those that had R0 resection performed.	Up to 40 weeks
Number of Participants With and Without Recurrence	Number of participants with and without recurrence following surgery. This outcome was updated when the results were entered.	Up to 40 weeks
Number of Participants: Progression Free Survival	Presented are count of patients that had experienced either progression free survival or disease progression through the follow up period.	Up to 2 years
Number of Participants: Overall Survival	Presented are counts of patients that we either deceased or not deceased at the end of the follow up period.	Up to 2 years
Grade 3 or Greater Acute and Late Gastrointestinal Toxicity	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. This outcome was clarified when results were entered. The number of patients that experienced at least 1 grade 3 (or greater) event are presented.	Up to 40 weeks

Collaborators and Investigators

• Sponsor: Yale University

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 26, 2017
• Primary Completion (ACTUAL): September 18, 2019
• Study Completion (ACTUAL): September 18, 2019

Study Registration Dates

• First Submitted: March 28, 2017
• First Submitted That Met QC Criteria: March 28, 2017
• First Posted (ACTUAL): April 4, 2017

Study Record Updates

• Last Update Posted (ACTUAL): October 27, 2022
• Last Update Submitted That Met QC Criteria: September 29, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Irinotecan
• Other Study ID Numbers: 2000020432

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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