Neoadjuvant Modified FOLFIRINOX and Stereotactic Body Radiation Therapy in Borderline Resectable Pancreatic Adenocarcinoma
Condition: Pancreatic Cancer
MeSH terms: Adenocarcinoma
Intervention: neoadjuvant mFOLFIRINOX; Stereotactic body radiotherapy (SBRT)
Intervention description: 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.; 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.
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: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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