Phase III Study of ABI-007(Albumin-bound Paclitaxel) Plus Gemcitabine Versus Gemcitabine in Metastatic Adenocarcinoma of the Pancreas

A Phase III, open-label randomized, multicenter trial to compare ABI-007(Albumin-bound Paclitaxel)in combination with gemcitabine administered weekly to standard treatment (gemcitabine monotherapy) with respect to overall survival, objective tumor response rate and Progression Free Survival (PFS) in patients diagnosed with metastatic adenocarcinoma of the pancreas.

Inclusion criteria

A participant will be eligible for inclusion in this study only if all of the following criteria are met:

• Participant has definitive histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas. The definitive diagnosis of metastatic pancreatic adenocarcinoma will be made by integrating the histopathological data within the context of the clinical and radiographic data. Participants with islet cell neoplasms are excluded.
• Initial diagnosis of metastatic disease must have occurred ≤6 weeks prior to randomization in the study.
• Patient has one or more metastatic tumors measurable by Computed Tomography (CT) scan or Magnetic resonance imaging (MRI), if patient is allergic to CT contrast media).
• Male or non-pregnant and non-lactating female, and ≥ 18 years of age. 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 (β-hCG) documented 72 hours prior to the first administration of study drug.

If sexually active, the patient must agree to use contraception considered adequate and appropriate by the Investigator during the period of administration of study drug. In addition, male and female patients must utilize contraception after the end of treatment as recommended in the product's Summary of Product Characteristics or Prescribing Information provided in the study manual.

• Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. Prior treatment with 5-Fluorouracil (5-FU) or gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present. Patients having received cytotoxic doses of gemcitabine or any other chemotherapy in the adjuvant setting are not eligible for this study.
• Patient has adequate biological parameters as demonstrated by the following blood counts at Baseline (obtained ≤14 days prior to randomization):

Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L; Platelet count ≥ 100,000/mm^3 (100 × 10^9/L); Hemoglobin (Hgb) ≥ 9 g/dL.

• Patient has the following blood chemistry levels at Baseline (obtained ≤14 days prior to randomization):

Aspartate Transaminase (AST), Serum Glutamic-Oxaloacetic Transaminase (SGOT), Alanine Transaminase ( ALT) Serum Glutamic-Pyruvic Transaminase (SGPT) ≤ 2.5 × upper limit of normal range (ULN), unless liver metastases are clearly present, then ≤ 5 × ULN is allowed Total bilirubin ≤ ULN Serum creatinine within normal limits or calculated clearance ≥ 60 mL/min/1.73 m^2 for patients with serum creatinine levels above or below the institutional normal value. If using creatinine clearance, actual body weight should be used for calculating creatinine clearance (e.g., using the Cockroft-Gault formula). For patients with a Body Mass Index (BMI) >30 kg/m^2, lean body weight should be used instead.

• Patient has acceptable coagulation studies (obtained ≤14 days prior to randomization) as demonstrated by prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits (± 15%).
• Patient has no clinically significant abnormalities in urinalysis results (obtained ≤14 days prior to randomization).
• Patient has a Karnofsky performance status (KPS) ≥ 70. Two observers will be required to assess KPS. If discrepant, the one with the lowest assessment will be considered true.
• Patients should be asymptomatic for jaundice prior to Day 1. Significant or symptomatic amounts of ascites should be drained prior to Day 1. Pain symptoms should be stable and should not require modifications in analgesic management prior to Day 1.
• Patient has been informed about the nature of the study, and has agreed to participate in the study, and signed the Informed Consent Form (ICF) prior to participation in any study-related activities.

Exclusion criteria

A patient will not be eligible for inclusion in this study if any of the following criteria apply:

• Patient has known brain metastases, unless previously treated and well-controlled for at least 3 months (defined as clinically stable, no edema, no steroids and stable in 2 scans at least 4 weeks apart).
• Patient has only locally advanced disease.
• Patient has experienced a ≥10% decrease in KPS between baseline visit and within 72 hours prior to randomization.
• Patient has a ≥20% decrease in serum albumin level between baseline visit and within 72 hours prior to randomization.
• History of malignancy in the last 5 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Patients with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease-free for at least 5 years.
• Patient uses Coumadin.
• Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
• Patient has known historical or active infection with Human Immunodeficiency Virus (HIV), hepatitis B, or hepatitis C.
• Patient has undergone major surgery, other than diagnostic surgery (i.e.--surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of treatment in this study.
• Patient has a history of allergy or hypersensitivity to any of the study drugs or any of their excipients, or the patient exhibits any of the events outlined in the Contraindications or Special Warnings and Precautions sections of the product or comparator Summary of Product Characteristics (SmPC) or Prescribing Information.
• History of connective tissue disorders (e.g., lupus, scleroderma, arteritis nodosa).
• Patients with a history of interstitial lung disease.
• History of chronic leukemias (e.g., chronic lymphocytic leukemia).
• Patients with high cardiovascular risk, including, but not limited to, recent coronary stenting or myocardial infarction in the past year.
• History of Peripheral Artery Disease (e.g,. claudication, Leo Buerger's disease).
• Patient has serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders, which could compromise the patient's safety or the study data integrity.
• Patient is enrolled in any other clinical protocol or investigational trial.
• Patient is unwilling or unable to comply with study procedures, or is planning to take vacation for 7 or more consecutive days during the course of the study.