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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Dose Escalation Safety Study of Locally-Delivered (Intra-Arterial) Gemcitabine in Unresectable Adenocarcinoma of the Pancreas

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Gemcitabine, local delivery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects will be eligible to participate in the study if all of the following criteria are met: Males and female subjects 18 years of age and older. Subjects with locally advanced unresectable adenocarcinoma (cytological or histologic proof required) of the pancreas.. Patients with islet cell tumors are not eligible. 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. Karnofsky Performance Status (KPS) >60. Adequate renal, and bone marrow function described as: Leukocytes ≥ 3,000/uL Absolute neutrophil count ≥ 1,500/uL Platelets ≥100,000/uL 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. Hemoglobin ≥8.5 g/dL (may be receiving supportive therapy) PT/PTT (WNL) Adequate Hepatic function (endoscopic or percutaneous drainage as needed) described as: Total bilirubin ≤3 times UNL (less than or equal to 2 mg/dL) AST (SGOT)/ALT (SGPT) ≤ 5 times ULN or ≤5 times ULN in the setting of liver metastases. Lipase and Amylase within normal limits. 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: Have a known sensitivity to gemcitabine. 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. Evidence of coagulopathy. Inability or unwillingness to comply with study procedures and/or follow-up procedures. Evidence of infection or other coexisting medical condition, which in the opinion of the investigator would preclude administration of gemcitabine. Patients with uncontrolled congestive heart failure, unstable angina and myocardial infarction within 3 months. Female patient who is pregnant, nursing or planning on becoming pregnant. 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. Have known brain metastases. Have had any major surgery within four weeks of enrollment. Have any clinically detectable ascites. Have uncontrolled concomitant illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. Have serious medical or psychiatric illness that could, in the Investigator's opinion, potentially interfere with the completion of treatment according to this protocol. 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). Have had any chemotherapy or systemic corticosteroids within 2 weeks of study entry. Have acquired, hereditary or congenital immunodeficiency's including cellular immunodeficiencies, hypogammaglobulinemia and dysgammaglobulinemia or hepatitis. Have a prior history of a documented hemolytic event. Is HIV-positive or Hepatitis positive.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional 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)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Gemcitabine, Local Delivery (Dose 1)<br>Gemcitabine; 1 cycle, two doses per cycle; 250mg/m2 dose | Drug: Gemcitabine, local delivery<br>* Intra-arterial targeted drug delivery<br>* Other names: Gemzar;|
| Other: Gemcitabine, Local Delivery (Dose 2)<br>Gemcitabine; 1 cycle, two doses per cycle; 500mg/m2 dose | Drug: Gemcitabine, local delivery<br>* Intra-arterial targeted drug delivery<br>* Other names: Gemzar;|
| Other: Gemcitabine, Local Delivery (Dose 3)<br>Gemcitabine; 1 cycle, two doses per cycle; 750mg/m2 dose | Drug: Gemcitabine, local delivery<br>* Intra-arterial targeted drug delivery<br>* Other names: Gemzar;|
| Other: Gemcitabine, Local Delivery (Dose 4)<br>Gemcitabine; 1 cycle, two doses per cycle; 1000mg/m2 dose | Drug: Gemcitabine, local delivery<br>* Intra-arterial targeted drug delivery<br>* Other names: Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the Maximum Tolerated Dose of Gemcitabine to be Delivered Locally to the Pancreas | Maximum Tolerated Dose (MTD) of gemcitabine administered intra-arterially to the pancreatic tumor(s) using the RenovoCath™ RC120 catheter. One week post treatment, toxicities will be assessed to determine if there is a pre-defined Dose Limiting Toxicity necessitating dose stopping or holding. | 1 week post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CA19-9 Tumor Reduction | Measurements of CA19-9 tumor marker are measured pre-treatment and at various time points (starting with one week) post treatment. | 1 week after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic cancer, unresectable, gemcitabine, device, local delivery, chemoembolization