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

 1. 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.

 2. Initial diagnosis of metastatic disease must have occurred ≤6 weeks prior to
 randomization in the study.

 3. 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).

 4. 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.

 5. 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.

 6. 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.

 7. 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.

 8. 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%).

 9. Patient has no clinically significant abnormalities in urinalysis results (obtained
 ≤14 days prior to randomization).

 10. 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.

 11. 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.

 12. 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:

 1. 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).

 2. Patient has only locally advanced disease.

 3. Patient has experienced a ≥10% decrease in KPS between baseline visit and within 72
 hours prior to randomization.

 4. Patient has a ≥20% decrease in serum albumin level between baseline visit and within
 72 hours prior to randomization.

 5. 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.

 6. Patient uses Coumadin.

 7. Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring
 systemic therapy.

 8. Patient has known historical or active infection with Human Immunodeficiency Virus
 (HIV), hepatitis B, or hepatitis C.

 9. 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.

 10. 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.

 11. History of connective tissue disorders (e.g., lupus, scleroderma, arteritis nodosa).

 12. Patients with a history of interstitial lung disease.

 13. History of chronic leukemias (e.g., chronic lymphocytic leukemia).

 14. Patients with high cardiovascular risk, including, but not limited to, recent coronary
 stenting or myocardial infarction in the past year.

 15. History of Peripheral Artery Disease (e.g,. claudication, Leo Buerger's disease).

 16. 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.

 17. Patient is enrolled in any other clinical protocol or investigational trial.

 18. 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.