Gemcitabine Plus Albumin-bound Paclitaxel In Patients With Advanced Metastatic Pancreatic Cancer

A Phase I Trial of Gemcitabine (Gemzar) Plus ABI-007 (ABRAXANE) In Patients With Advanced Metastatic Pancreatic Cancer

To determine the maximum tolerated dose and dose-limiting toxicity of Gemcitabine plus Albumin-bound paclitaxel (ABI-007) in patients with advanced metastatic pancreatic cancer.

Albumin-bound paclitaxel is a novel, solvent-free, albumin-bound, 130 nanometer particle form of paclitaxel designed to avoid the problems associated with solvents used in Taxol(Abraxane prescribing information 2005). Albumin has a number of properties that make it an attractive molecule to combine with paclitaxel. Albumin is a natural transporter of endogenous hydrophobic molecules such as water-insoluble vitamins and hormones (Vorum 1999)and albumin binding to the gp-60 receptor (albondin) initiates the caveolae-mediated endothelial transport of protein-bound and unbound plasma constituents (John et al 2003, Minshall et al 2003, Tiruppathi et al 1997).

This study consisted of a Phase 1 dose escalation phase, a Phase 2 treatment phase and a 24-month follow-up phase.

Inclusion Criteria:

• Patient has histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas. Patients with islet cell neoplasms are excluded.

• Male or non-pregnant and non-lactating female, and age greater or equal to 18.

  • If a female patient is of child-bearing potential, as evidenced by regular menstrual periods, she must have a negative serum pregnancy test beta-human chorionic gonadotropin (B-hCG) documented within 72 hours of the first administration of study drug.
  • If sexually active, the patient must agree to use contraception considered adequate and appropriate by the investigator.

• Patient must have received no prior therapy for the treatment of metastatic disease. Prior treatment with 5-fluorouracil (5-FU) or gemcitabine administered as a radiation sensitizer during and up to 4 weeks after radiation therapy is allowed. If a patient received gemcitabine in the adjuvant setting, tumor recurrence must have occurred at least 6 months after completing the last dose of gemcitabine.

• Patient has the following blood counts at baseline

  • Absolute neutrophil count (ANC) equal or greater to 1.5 x 10^9/L;
  • Platelets equal or greater to 100 x 10^9/L
  • Hemoglobin equal or greater to 9 g/dL.
  • Patient has the following blood chemistry levels at baseline:
  • Aspartate aminotransferase (SGOT), Alanine aminotransferase (SGPT) equal or less than 2.5 x upper limit of normal range (ULN) is allowed
  • Bilirubin less than or equal to ULN
  • Serum creatinine within normal limits or calculated clearance equal or greater to 60 mL/min/1.73M^2 patients with serum creatinine levels above the institutional normal value

• Patient has no clinically significant abnormalities in urinalysis results

• Patient has acceptable coagulation status as indicated by a prothrombin time (PT) within normal limits (plus or minus 15%) and partial thromboplastin time (PTT) within normal limits (plus or minus 15%).

• Patient has a Karnofsky performance status (KPS) greater or equal to 70 (Eastern Cooperative Oncology Group [ECOG] PS 0-1).

• Patient has one or more metastatic tumors measurable by computed tomography (CT) scan.

• Patient has been informed about the nature of study, and has agreed to participate in the study, and signed the Informed Consent form prior to participation in any study-related activities.

Exclusion Criteria:

• Patient has known brain metastases unless previously treated and well controlled for at least 3 months (defined as stable clinically, no edema, no steroids and stable in two scans at least 4 weeks apart).
• Patient uses therapeutic coumadin for a history of pulmonary emboli and deep vein thrombosis (DVT).
• Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
• Patient has known infection with human immunodeficiency virus (HIV), hepatitis B, hepatitis C.
• Patient has undergone major surgery, other than diagnostic surgery i.e.-- done to obtain a biopsy for diagnosis without removal of an organ), with 4 weeks prior to Day 1 of treatment in this study.
• Patient received radiotherapy, surgery, chemotherapy, or an investigational therapy within 3 weeks prior to study entry weeks (6 weeks for nitrosureas or mitomycin C).
• Patient has a history of allergy or hypersensitivity to the study drug.
• Patient has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug.
• Patient is unwilling or unable to comply with study procedures.
• Patient is enrolled in any other clinical protocol or investigational trial.