Patient case: 57-year-old female with Pancreatic adenocarcinoma. Genetic variant: RB1, TP53, KRAS. Other conditions: None.

Clinical trial: Neoadjuvant GMCI Plus mFOLFIRINOX and Chemoradiation for Non-Metastatic Pancreatic Adenocarcinoma

Summary: The study will investigate if the addition of GMCI to neoadjuvant mFOLFIRINOX + chemoradiation is safe and improves the clinical outcome of borderline resectable and unresectable locally advanced pancreatic adenocarcinoma, as measured by resection rate, progression-free survival and overall survival.

Detailed description: The current protocol is designed to delivery multiple courses of GMCI timed with a series of neoadjuvant debulking therapies- modified FOLFIRINOX (mFX) chemotherapy followed by gemcitabine-radiation (GR) followed by surgery- to capitalize on the synergies with the different treatment modalities.
  This protocol includes two phases: Phase 1b followed by Phase 2. The Phase 1b evaluates the safety and feasibility of mFX+GR+surgery in combination with GMCI. Patients will be enrolled on the Phase 1b based on the definition of dose limiting toxicity (DLT), waiting periods and stopping rules described in the protocol. The Phase 2 is a randomized study comparing a test group receiving GMCI added to mFX+GR+surgery to a control arm receiving mFX+GR followed by surgery.

Eligibility: Inclusion Criteria:
  -  Pathological diagnosis of pancreatic adenocarcinoma before first treatment but may be enrolled with presumed diagnosis based on clinical and radiologic evaluation with confirmation made by biopsy at time of EUS prior to AdV-tk injection
  -  Patients must be deemed to be in adequate health to undergo major surgery (pancreaticoduodenectomy)
  -  Tumor accessible for injection that is classified as borderline-resectable or locally advanced but considered potentially resectable after central review by surgical investigators. Resection may include major vascular resection with reconstruction as needed.
  -  Age 18-76 years
  -  Performance status ECOG 0-1
  -  SGOT (AST)<3x upper limit of normal
  -  Total bilirubin ≤2mg/dl
  -  Creatinine<2mg/dl
  -  Calculated creatinine clearance >30ml/m
  -  WBC>3000/mm3
  -  Absolute neutrophil count (ANC)>1500/mm3
  -  Platelets>100,000/mm3
  -  Hemoglobin > 9 g/dL.
  -  Patients must give study specific informed consent prior to enrollment
  Exclusion Criteria:
  -  Baseline peripheral sensory neuropathy ≥ grade 2
  -  Primary hepatic dysfunction including known cirrhosis or active hepatitis. Patients with biliary obstruction must be stented prior to initiating treatment.
  -  Evidence of clinically significant pancreatitis as determined by the investigator
  -  Evidence of significant ascites as determined by the investigator
  -  Patients on systemic corticosteroids (>10 mg prednisone per day or equivalent) or other systemic immunosuppressive drugs
  -  Known to be HIV+
  -  Pregnant or breast-feeding. Female patients of childbearing age must have negative serum or urine pregnancy test within 1 week of beginning therapy.
  -  Other current malignancy (except squamous or basal cell skin cancers)
  -  Prior abdominal radiation therapy or prior chemotherapy for pancreatic cancer
  -  Other serious co-morbid illness or compromised organ function
  -  Known sensitivity or allergic reactions to acyclovir or valacyclovir

Relevance to patient case: not relevant