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
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      Background:

        -  Pancreatic cancer is the fourth leading cause of cancer death in the United States.

        -  Surgery offers the only chance at cure; however, less than 20% of patients are
           considered resectable at initial presentation.

        -  A common reason for being classified as unresectable is loco-regional advanced disease.

        -  Several phase I studies of regional administration of chemotherapy have proven safe.

        -  The main advantage of pancreatic cancer targeted arterial perfusion of Gemcitabine is
           achievement of higher local bio-available active drug levels at the tumor bed.

        -  The Regional Chemotherapy in Locally Advanced Pancreatic Cancer (RECLAP) trial is a
           phase I trial offering highly selective 24-hour intra-arterial administration of
           Gemcitabine via a subcutaneous port for patients with unresectable locally-advanced
           pancreatic cancer.

      Objectives:

      Primary Objective:

        -  To evaluate feasibility and toxicity of intra-arterial gemcitabine therapy (dose
           limiting toxicity (DLT)).

        -  To establish the maximum tolerated dose (MTD)

      Secondary Objectives:

        -  To evaluate response rate using Response Evaluation Criteria in Solid Tumors (RECIST),
           positron emission tomography (PET), magnetic resonance imaging (MRI) and computed
           tomography (CT) perfusion criteria (European Association for the Study of the Liver
           (EASL))

        -  To determine progression free and overall survival.

        -  To evaluate the conversion rate from unresectable or borderline resectable to
           potentially resectable pancreatic cancer.

        -  To determine progression-free and overall survival.

        -  To analyze potential selection criteria to be used in future studies for patients who
           present with marginally unresectable or unresectable locally-advanced pancreatic cancer
           that might benefit from this approach.

      Eligibility:

        -  Unresectable locally-advanced pancreatic cancer.

        -  18 years old or greater with an Eastern Cooperative Oncology Group (ECOG) 0-2

        -  Laboratory and physical examination parameters within acceptable limits by standard of
           practice guidelines prior to surgery or chemotherapy.

        -  No extra-pancreatic disease except regional lymph nodes.

      Design:

        -  This is a dose escalation phase-I study.

        -  Patients considered unresectable due to locally-advanced pancreatic cancer will receive
           selective arterial perfusion of gemcitabine over 24 hours via a subcutaneous indwelling
           port.

        -  Treatment will be given on Days 1 and 14. One cycle = 4 weeks for up to six cycles.

        -  Three to six patients will be enrolled per dose cohort.

        -  18 to 36 patients in 7 cohorts will be accrued plus 6 more patients at the maximum
           tolerated dose (MTD over 36 months. Patients will be evaluated every 2 cycles (8 weeks).
           Upon progression patients will be taken off study. If no progressive disease (PD),
           patients will continue up to 6 cycles.

        -  Chemotherapy na(SqrRoot) ve patients and patients who received previously chemotherapy
           including gemcitabine will be allowed, as this mode of administration has better
           bioavailability, offer potential for better biological effect and less systemic toxicity
           profiles.
    

Intervention name(s): Gemcitabine
Intervention type(s): Drug
Intervention description(s): 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.
Other intervention name(s): Gemzar
Intervention MeSH terms: Gemcitabine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Pancreatic Cancer; Regional Therapy; Selective Arterial Infusion; Locally Advanced Disease