Perioperative FOLFIRINOX for Patients With Resectable Pancreatic Adenocarcinoma: A Pilot Study

The purpose of this study is to see whether it is possible to give 8 doses of a combination of chemotherapy called FOLFIRINOX before surgery in subjects whose pancreas cancer can be removed with surgery.

Study Overview

• Status: Terminated
• Conditions: Pancreatic Ductal Adenocarcinoma (PDAC)
• Intervention / Treatment: Drug: FOLFIRINOX (oxaliplatin, leucovorin, irinotecan)

Detailed Description

Primary Objective: To evaluate the percentage of pancreatic cancer patients able to complete the full 4 months of preoperative chemotherapy and undergo a resection.

Secondary Objectives

• To assess the percentage of patients able to complete all therapy, including preoperative chemotherapy, surgery, and postoperative therapy.
• To assess treatment-related toxicity during preoperative therapy
• To assess intra-operative and post-operative complications
• To assess the histopathologic (R0/R1) resection rate after preoperative therapy
• To determine disease free survival (DFS) for patients who undergo resection.
• To determine progression free survival (PFS) for all patients
• To determine overall survival (OS) from the date of first treatment

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Histologic or cytologic diagnosis of adenocarcinoma of the pancreas.

2. Resectable primary tumor of the head, body or tail of the pancreas defined per NCCN Guidelines version 2.2015:

   • No extra-pancreatic disease, aside from lymphadenopathy
   • No arterial tumor contact (celiac axis, superior mesenteric artery, or common hepatic artery)
   • No tumor contact with the superior mesenteric vein or portal vein or ≤ 180° contact without vein contour irregularity
3. Confirmation of resectability by surgical oncology consultation.
4. No previous therapy for pancreatic cancer
5. Short removable metal stents rather than plastic stents are strongly encouraged but not required for palliation of initial obstructive jaundice
6. ECOG performance status of 0 or 1 (Appendix 1)
7. Age > 18 years
8. No CVA within 6 months, no MI within 6 months
9. The effects of mFOLFIRINOX on the developing human fetus are unknown. For this reason and because chemotherapy agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
10. Negative pregnancy test in females of reproductive age
11. Anticoagulation is permitted but patients may not be on warfarin.

12. Patients must have normal organ and marrow function as defined below:

    • absolute neutrophil count >1,500/mcL
    • platelets >100,000/mcL
    • total bilirubin < 1.5X upper limits of normal
    • AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal
    • creatinine within normal institutional limits OR
    • creatinine clearance >60 mL/min/ per Cockroft-Gault equation for patients with creatinine levels above institutional normal.
13. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Patients who have had previous chemotherapy or radiotherapy for pancreatic adenocarcinoma prior to entering the study.
2. Pathologic subtypes other than pure adenocarcinoma; acinar cell carcinoma, squamous cell carcinoma, spindle cell carcinoma, neuroendocrine cancer, and mixed types are not eligible.
3. Patients who are receiving any investigational agents.
4. Patients with borderline resectable, locally advanced or metastatic disease.
5. History of allergic reactions attributed to 5-FU, leucovorin, irinotecan or oxaliplatin or to compounds of similar chemical or biologic composition.
6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active liver disease including viral or non-viral hepatitis and cirrhosis, chronic diarrhea or inflammatory disease of the colon or rectum, or psychiatric illness/social situations that would limit compliance with study requirements.
7. Pregnant women are excluded from this study. mFOLFIRINOX is a regimen containing more than one chemotherapy agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with mFOLFIRINOX, breastfeeding should be discontinued if the mother is treated with these agents. These potential risks may also apply to other agents used in this study.
8. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with mFOLFIRINOX. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
9. Currently active second malignancy other than non-melanoma skin cancer or carcinoma in-situ of the cervix. Patients are not considered to have a "currently active" malignancy if they have completed therapy and have no evidence of recurrence for at least 5 years.
10. Pre-existing neuropathy greater than grade 1.
11. Inflammatory bowel disease that is uncontrolled or on active treatment (Crohn's disease, ulcerative colitis).

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: FOLFIRINOX+surgery; 4 cycles of pre-operative FOLFIRINOX, followed by surgery, followed by 2 more cycles of FOLFIRINOX	Drug: FOLFIRINOX (oxaliplatin, leucovorin, irinotecan); FOLFIRINOX administered preoperatively and postoperatively

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients able to complete 4 months of preoperative chemotherapy and undergo a resection	Measured by percentage of successes/failures	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The extent of preoperative chemotherapy, surgery, and adjuvant chemotherapy.	Reported as a yes/no for each element of therapy.	6 months
Presence of adverse events	Presence of grade 3 and 4 toxicities measured according to NCI CTCAE version 4.0.	6 months
Intraoperative and post-op complications	Any unexpected events as determined by surgical oncologist	Within 6 weeks post surgery
R0/R1 resection rates	Measured as proportion of patients with microscopic negative and microscopic residual tumor margin	6 months
Disease free survival	Defined by date from surgical resection to radiographic recurrence or death	Up to 5 years
Progression free survival	Defined by radiographic progression by RECIST criteria or death	Up to 5 years
Overall survival	Defined by date from Cycle 1 Day 1 of preoperative chemotherapy to death from any cause.	Up to 5 years

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Hedy Kindler, M.D., University of Chicago

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2016
• Primary Completion (Actual): March 29, 2018
• Study Completion (Actual): March 29, 2018

Study Registration Dates

• First Submitted: May 16, 2016
• First Submitted That Met QC Criteria: May 20, 2016
• First Posted (Estimate): May 25, 2016

Study Record Updates

• Last Update Posted (Actual): March 19, 2019
• Last Update Submitted That Met QC Criteria: March 15, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Pancreatic ductal adenocarcinoma; FOLFIRINOX; resectable pancreatic cancer
• 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; Antineoplastic Agents; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Oxaliplatin; Leucovorin; Irinotecan; Folfirinox
• Other Study ID Numbers: IRB15-1630

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No