A Pilot Study of Pre- and Post-surgery Chemotherapy With mFOLFIRINOX in Localized, Resectable Pancreatic Adenocarcinoma
Condition: Pancreatic Adenocarcinoma
MeSH terms: Adenocarcinoma
Intervention: 5 Fluorouracil; Leucovorin; Irinotecan; Oxaliplatin
Intervention description: 2400 mg/m2 by continuous intravenous infusion over 46 hours; 400 mg/m2 by IV infusion over 2 hours; 180 mg/m² IV infusion on Day 1 over 90-120 minutes (infusion via a Y connector during the infusion of leucovorin); 85 mg/m² IV infusion on Day 1 over 2 hours
Intervention MeSH terms: Leucovorin; Fluorouracil; Oxaliplatin; Irinotecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: neoadjuvant; chemotherapy; resectable; adjuvant; pancreas; cancer; adenocarcinoma; surgery

Summary:

      The purpose of the study is to demonstrate that it is possible to administer chemotherapy
      prior to and following surgery for pancreatic cancer which is considered operable. The
      chemotherapy chosen is that which has been shown to be the most effective in treating
      metastatic disease, and the goal is both to investigate whether this is tolerable and also to
      investigate the efficacy of this approach in terms of disease response and survival.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologic or cytologic diagnosis of adenocarcinoma of the pancreas.

          -  Resectable primary tumor of the head, body or tail of the pancreas defined as a
             visible mass in the pancreas and:

          -  No extrapancreatic disease

          -  A patent superior mesenteric (SMV)- portal vein (PV) confluence (assuming the
             technical ability to resect and reconstruct this venous confluence if needed)

          -  A definable tissue plane between the tumor and regional arterial structures including
             the celiac axis, common hepatic artery, and SMA.

          -  Confirmation of resectability by surgical oncology consultation.

          -  Presentation at a multidisciplinary conference at either University of Chicago or
             NorthShore University

          -  No previous therapy for pancreatic cancer

          -  Short removable metal stents rather than plastic stents are preferred but not required
             for palliation of initial obstructive jaundice

          -  Karnofsky performance status 80 or better

          -  Age > 21 years

          -  No currently active second malignancy

          -  No CVA within 6 months, no MI within 6 months

          -  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.

          -  Negative pregnancy test in females of reproductive age

          -  Life expectancy of greater than 3 months.

          -  Anticoagulation is permitted but patients may only be on lovenox for this purpose.

          -  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 Cockcroft-Gault equation for patients with
                  creatinine levels above institutional normal.

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Patients who have had previous chemotherapy or radiotherapy for pancreatic
             adenocarcinoma prior to entering the study.

          -  Pathologic subtypes other than pure adenocarcinoma; acinar cell carcinoma, squamous
             cell carcinoma, spindle cell carcinoma, neuroendocrine cancer, and mixed types are not
             eligible.

          -  Patients who are receiving any investigational agents.

          -  Patients with borderline resectable, locally advanced or metastatic disease.

          -  History of allergic reactions attributed to 5FU, leucovorin, irinotecan or oxaliplatin
             or to compounds of similar chemical or biologic composition.

          -  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.

          -  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 FOLFIRINOX, 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.

          -  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.

          -  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.

          -  Pre-existing neuropathy greater than grade 1.

          -  Anticoagulants other than low molecular weight heparin.