A Dose Escalation Safety Study of Locally-Delivered Gemcitabine in Pancreatic Cancer

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.

Patients diagnosed with unresectable pancreatic cancer who may or may not have had prior chemotherapy or radiation therapy may be eligible to enroll in this dose escalation study to determine the maximum tolerated dose of gemcitabine to be delivered locally to the pancreatic tumors using the RenovoCath R120 catheter. Patients enrolled may receive up to 8 catheterizations for delivering gemcitabine directly to the pancreatic tumors starting at a reduced dose( 1/4 of standard i.v. gemcitabine dose), then every two doses, increase the dose by 25% if there are no toxicities up to a maximum dose of 1000 mg/m2. There are four cycles, with two doses per cycle. Imaging studies will be conducted as well as assessment for standard, myelosuppresive and gastric toxicities will be assessed. Pain will also be measured throughout the study.

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.