Regional Chemotherapy in Locally Advanced Pancreatic Cancer: RECLAP Trial
Condition: Histologically or Cytologically Confirmed Pancreatic Ca; Unresectable or Borderline Resectable Pancreatic Ca
MeSH terms: Pancreatic Neoplasms
Intervention: Gemcitabine
Intervention description: Gemcitabine starting dose was 18mg/m(2)/24h via infusion pump on days 1-14. One cycle = 4 weeks for up to six cycles. Three to six patients enrolled per dose cohort. Patients were dosed at successive higher doses until maximum tolerated dose or up to 165 mg/m(2)/24h.
Intervention MeSH terms: Gemcitabine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Pancreatic Cancer; Regional Therapy; Selective Arterial Infusion; Locally Advanced Disease

Summary:

      Background:

      - Pancreatic cancer is difficult to treat because by the time most cases are diagnosed, the
      tumors are too large to be removed surgically. Standard intravenous chemotherapy may shrink
      some of the tumor, but even with chemotherapy only about 25 percent of patients will live for
      1 year following diagnosis. Several preliminary studies have shown that it is safe to give
      chemotherapy directly into the pancreas in the area of the tumor, and that giving gemcitabine
      over a longer period increases the amount of drug that is available to the tumor. Researchers
      are interested in studying whether giving the approved pancreatic cancer chemotherapy drug
      gemcitabine directly into the pancreas in the area of the cancer and at a slow rate of
      infusion is a safe and effective treatment.

      Objectives:

      - To test the safety and effectiveness of administering gemcitabine directly to a pancreatic
      tumor at a slow rate of infusion.

      Eligibility:

      - Individuals at least 18 years of age who have been diagnosed with pancreatic cancer that is
      currently too large to be removed surgically but has not yet spread to other organs.

      Design:

        -  Participants will be screened with a full medical history and physical examination,
           blood and urine tests, and imaging studies.

        -  Participants will undergo pancreatic angiography and embolization, during which a
           catheter will be threaded into the blood vessels near the pancreas and a contrast dye
           will be used to show the blood vessels supplying the tumor. These blood vessels will
           then be surgically closed off.

        -  After the embolization, gemcitabine will be given as an infusion into the area around
           the tumor over 24 hours.

        -  Participants will return to the clinical center every 2 weeks after the first infusion
           for additional infusions of gemcitabine, using the same procedures as above.
           Participants will be monitored with frequent blood tests and imaging studies.

        -  Two weeks after the fourth treatment (course 1), participants will have more imaging
           studies, a physical examination, and blood tests. If the tumor is shrinking,
           participants will have two more courses of treatment (eight more infusions of
           gemcitabine).

        -  Participants will have followup visits every 3 months for 2 years following the last
           treatment and then every 6 months.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Histologically or cytologically confirmed locally advanced pancreatic adenocarcinoma
             or clinical and radiographic evidence of pancreatic cancer

        Note: Patients with a limited disease burden outside the pancreas, who have undergone
        systemic chemotherapy for metastatic disease and have achieved a complete response on the
        metastatic lesions of greater than or equal to 6 months, and have no evidence of disease
        outside the pancreas at time of enrollment, are eligible.

          -  Disease must be evaluable

          -  Disease should be deemed unresectable by the MD Anderson criteria

          -  Patients may be chemo naive or have received prior chemotherapy (including
             Gemcitabine) and/or radiation

          -  Greater than or equal to 18 years of age

          -  Must be able to understand and sign the Informed Consent Document

          -  Clinical performance status of Eastern Cooperative Oncology Group (ECOG) less than or
             equal to 2

          -  Life expectancy of greater than three months

          -  Patients of both genders must be willing to practice birth control during and for four
             months after receiving chemotherapy

          -  Hematology:

               -  Absolute neutrophil count greater than 1300/mm(3) without the support of
                  Filgrastim.

               -  Platelet count greater than 75,000/mm(3).

               -  Hemoglobin greater than 8.0 g/dl.

          -  Chemistry:

               -  Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less or
                  equal to 3 times the upper limit of normal, unless patient carries a biliary
                  stent. For these patients, to account for asymptomatic, transient elevations in
                  transaminases ('transaminitis'), serum ALT/AST may be less than or equal to 5
                  times the upper limit of normal provided all other eligibility parameters are
                  met.

               -  Serum creatinine less than or equal to 1.8 mg/dl unless the measured creatinine
                  clearance is greater than 60 mL/min/1.73 m(2)

               -  Total bilirubin less than or equal to 2 mg/dl,

               -  Prothrombin time (PT) within 2 seconds of the upper limit of normal or
                  International Normalized Ratio (INR) less than or equal to 1.8

          -  No history of prior/other malignancies within the 2 years prior to enrollment with the
             exception of basal cell carcinoma

        EXCLUSION CRITERIA:

          -  Metastatic disease including malignant ascites

          -  Women of child-bearing potential who are pregnant or breastfeeding because of the
             potentially dangerous effects of the chemotherapy on the fetus or infant.

          -  Active systemic infections, coagulation disorders or other major medical illnesses of
             the cardiovascular, respiratory or immune system, myocardial infarction, heart failure

          -  Childs B or C cirrhosis or with evidence of severe portal hypertension by history,
             endoscopy, or radiologic studies

          -  Weight less than 40 kg

          -  Significant ascites, greater than 1000cc in the absence of peritoneal disease

          -  Concomitant medical problems that would place the patient at an unacceptable risk for
             the procedure

          -  Need for concurrent chemotherapy

          -  Discretion of the principal investigator (PI)