A Dose Escalation Safety Study of Locally-Delivered Gemcitabine in Pancreatic Cancer
Condition: Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: Gemcitabine, local delivery
Intervention description: Intra-arterial targeted drug delivery
Intervention MeSH terms: Gemcitabine
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Subjects receive a gradual increase of drug dose, until the full systemic dose is administered. Cycle 1: 250mg/m2. Cycle 2: 500mg/m2. Cycle 3: 750mg/m2. Cycle 4: 1000mg/m2.
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: pancreatic cancer; unresectable; gemcitabine; device; local delivery; chemoembolization

Summary:

      A dose escalation, safety study of local (intra-arterially) delivered gemcitabine to the
      pancreas using the RenovoCath R120 catheter to determine the maximum tolerated dose.
    

Eligibility criteria:

        Inclusion Criteria:

        Subjects will be eligible to participate in the study if all of the following criteria are
        met:

          1. Males and female subjects 18 years of age and older.

          2. Subjects with locally advanced unresectable adenocarcinoma (cytological or histologic
             proof required) of the pancreas.. Patients with islet cell tumors are not eligible.

          3. No clinical evidence of distant metastases, excluding single liver metastasis and
             local lymph node involvement. Patients with more than a single liver metastasis and/or
             other metastases who have already failed systemic chemotherapy and/or are on a break
             from systemic chemotherapy who are not surgical candidates can also qualify for this
             study.

          4. Karnofsky Performance Status (KPS) >60.

          5. Adequate renal, and bone marrow function described as:

               1. Leukocytes ≥ 3,000/uL

               2. Absolute neutrophil count ≥ 1,500/uL

               3. Platelets ≥100,000/uL

               4. Serum creatinine ≥2.0 mg/dL. Creatinine less than or equal to 1.5 mg/dL or
                  creatinine clearance greater than 40 mL/min/1.73 m2 for patients with creatinine
                  levels above institutional normal, as calculated by the Cockcroft Gault formula.

               5. Hemoglobin ≥8.5 g/dL (may be receiving supportive therapy)

               6. PT/PTT (WNL)

          6. Adequate Hepatic function (endoscopic or percutaneous drainage as needed) described
             as:

               1. Total bilirubin ≤3 times UNL (less than or equal to 2 mg/dL)

               2. AST (SGOT)/ALT (SGPT) ≤ 5 times ULN or ≤5 times ULN in the setting of liver
                  metastases.

               3. Lipase and Amylase within normal limits.

          7. Capable of understanding the purpose and risks of the study and willing to provide
             written informed consent and to comply with the procedures

        Exclusion Criteria:

        Subjects will be excluded from participation in the study if any of the following criteria
        are met:

          1. Have a known sensitivity to gemcitabine.

          2. Identification of metastatic disease, with the exception of single liver metastases or
             local lymph node involvement. Patients with more than a single liver metastasis and/or
             other metastases who have already failed systemic chemotherapy and/or are on a break
             from systemic chemotherapy who are not surgical candidates can also qualify for this
             study.

          3. Evidence of coagulopathy.

          4. Inability or unwillingness to comply with study procedures and/or follow-up
             procedures.

          5. Evidence of infection or other coexisting medical condition, which in the opinion of
             the investigator would preclude administration of gemcitabine.

          6. Patients with uncontrolled congestive heart failure, unstable angina and myocardial
             infarction within 3 months.

          7. Female patient who is pregnant, nursing or planning on becoming pregnant.

          8. Current enrollment and participation in another clinical study or prior exposure to an
             investigational agent within 12 weeks or 5 half-lives (whichever is longer) of
             anticipated dosing on Day 1 of this study.

          9. Have known brain metastases.

         10. Have had any major surgery within four weeks of enrollment.

         11. Have any clinically detectable ascites.

         12. Have uncontrolled concomitant illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac
             arrhythmia.

         13. Have serious medical or psychiatric illness that could, in the Investigator's opinion,
             potentially interfere with the completion of treatment according to this protocol.

         14. Other invasive malignancies within the past 3 years (with the exception of
             non-melanoma skin cancers, non-invasive bladder cancer or prostate cancer) not
             approved by the Medical Monitor (contact MM in event of prior diagnosis with
             malignancy to discuss enrollment status).

         15. Have had any chemotherapy or systemic corticosteroids within 2 weeks of study entry.

         16. Have acquired, hereditary or congenital immunodeficiency's including cellular
             immunodeficiencies, hypogammaglobulinemia and dysgammaglobulinemia or hepatitis.

         17. Have a prior history of a documented hemolytic event.

         18. Is HIV-positive or Hepatitis positive.