Combination Chemotherapy, and Radiation Therapy in Treating Patients With Locally Advanced Pancreatic Cancer
Condition: Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: fluorouracil; gemcitabine hydrochloride; leucovorin calcium; oxaliplatin; adjuvant therapy; conventional surgery; neoadjuvant therapy; radiation therapy
Intervention description: 2700 mg/m5 IV over 24 hr after gemcitabine weeks 1 & 2; Repeat one 3-week cycle starting day 22; 750 (females) or 900 (males) mg/m5 IV over 30 min (day 2)weeks 1 & 2; Repeat one 3-week cycle starting day 22; 20 mg/m5 PO (day 1) and 20 mg/m5 IV (day 2) weeks 1 and 2; Repeat one 3-week cycle starting day 22; 48 mg/m5 IV over 2 hr weeks 1, 2, 4, and 5; Patients who have undergone surgical resection, after post-operative recovery, will receive two additional cycles of gemcitabine/5-FU/leucovorin. Patients will then be followed at 3 month intervals with a history and physical exam, CT scan of the chest/abdomen/pelvis, and tumor markers.
If surgical resection is not possible, patients with stable or responsive disease will resume gemcitabine/5-FU/leucovorin and continue on it indefinitely until disease progression provided the patient tolerates it and wishes to remain on therapy.; Restaging with repeat imaging studies will be performed four weeks after completion of the chemo-radiation. If no contraindication for surgical resection is identified, resection will be performed six to eight weeks after completing chemoradiation. At the time of surgical resection, an extensive examination of the abdomen will be performed to exclude the presence of metastatic disease. All operations will be performed with curative intent with resection of all gross tumor (ie R0 [negative margins] or R1 [positive microscopic margins]). Resection of adjacent involved organs or vascular structures will be performed as clinically indicated.; Eligible patients will receive an initial two cycles of chemotherapy with gemcitabine 750 (females) or 900 (males) mg/m5 over 30 minutes followed by a 24-hour infusion of fluorouracil 2700 mg/m5 on days 2 and 9 of a 21-day cycle . Calcium leucovorin 20 mg/m5 will be given orally on days 1 and 8 and by IV push on days 2 and 9 prior to the 5-FU. A window of -2 up to +7 days will be allowed to start planned cycles of therapy provided all other criteria to restart the new cycle has been met. Patients will require a central venous catheter (Port, Hickman or Groshong catheter) for the administration of 5-FU.; A re-staging CT scan, which will be obtained as part of the radiation simulation, will be used to assess any possible response to the initial two cycles of chemotherapy. Unless the patient has developed evidence of metastatic disease, chemoradiation will proceed. Patients who required no treatment delays will commence chemoradiation on day 42. If a one-week delay is needed before cycle 2 of neo-adjuvant chemotherapy can be delivered, the patient will begin chemoradiation on day 49 provided treatment-related toxicity has resolved. If cycle 2 could not be given (2 or more week delay for resolution of treatment-related toxicity), then chemoradiation will begin once toxicity has resolved (may be earlier than day 42).
Intervention MeSH terms: Leucovorin; Folic Acid; Gemcitabine; Fluorouracil; Oxaliplatin; Calcium; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 19 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: adenocarcinoma of the pancreas; stage II pancreatic cancer; stage III pancreatic cancer

Summary:

      RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from
      dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage
      tumor cells. Giving combination chemotherapy with radiation therapy before surgery may shrink
      the tumor so that it can be removed.

      PURPOSE: This phase II trial is studying how well giving combination chemotherapy together
      with radiation therapy works in treating patients who may undergo surgery for locally
      advanced pancreatic cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of adenocarcinoma of the pancreas

             o Locally advanced disease

          -  Potentially resectable disease

          -  19 years of age and over

          -  Karnofsky 60-100%

          -  Absolute granulocyte count ≥ 2,000/mm^3

          -  Platelet count ≥ 100,000/mm^3

          -  Bilirubin ≤ 2.0 mg/dL (in the absence of biliary obstruction)

               -  If biliary obstruction is present, patients must undergo biliary decompression

               -  Bilirubin ≤ 3.0 mg/dL after biliary drainage has been established

          -  Creatinine ≤ 1.6 mg/dL

        Exclusion Criteria:

          -  No early stage resectable disease

          -  No concurrent non-steroidal anti-inflammatory medication

          -  No evidence of distant metastases to the liver or peritoneal area according to imaging
             studies and laparoscopic staging

          -  No symptomatic congestive heart failure

          -  No unstable angina pectoris

          -  No serious uncontrolled cardiac arrhythmia

          -  Not pregnant or nursing

          -  No uncontrolled illness

          -  No active or ongoing infection requiring IV antibiotics

          -  No marked intolerance to 5-fluoropyrimidines (i.e., fluorouracil, floxuridine,
             capecitabine, or fluorocytosine)

          -  No allergy to sulfonamides, aspirin, or non-steroidal anti-inflammatory drugs

          -  No allergy to platinum compounds or to antiemetics appropriate for administration in
             conjunction with study chemotherapy

          -  No other malignancy within the past 5 years except adequately treated basal cell or
             squamous cell skin cancer or adequately treated noninvasive carcinoma

          -  No prior chemotherapy for pancreatic cancer

          -  No prior abdominal radiotherapy