A Randomized Phase III Study of Weekly ABI-007 Plus Gemcitabine Versus Gemcitabine Alone in Patients With Metastatic Adenocarcinoma of the Pancreas

Inclusion Criteria

Inclusion Criteria

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

1. Patient 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. Patients 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 CT scan (or 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 (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-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 × 109/L; Platelet count ≥ 100,000/mm3 (100 ×
109/L); Hemoglobin (Hgb) ≥ 9 g/dL.

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

AST (SGOT), ALT (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 m2 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/m2, 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%). (See also Section 6.2 for Baseline PT/PTT analysis).

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 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 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.