Phase III Study of ABI-007(Albumin-bound Paclitaxel) Plus Gemcitabine Versus Gemcitabine in Metastatic Adenocarcinoma of the Pancreas
Condition: Metastatic Pancreatic Cancer
MeSH terms: Adenocarcinoma
Intervention: Albumin-bound paclitaxel (ABI-007); Gemcitabine
Intervention description: ABI-007 125 mg/m^2 administered by intravenous infusion; Gemcitabine, 1000 mg/m2 administered weekly for 7 weeks, Day 1 through Day 43 followed by a week of rest (Cycle 1), followed by cycles of weekly administration for 3 weeks, Days 1, 8, and 15 followed by a week of rest (Cycle 2 onward).
Intervention MeSH terms: Paclitaxel; Gemcitabine; Albumin-Bound Paclitaxel
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 861.0
Sex: All
Minimum age: 18 Years
Maximum age: 79 Years
Healthy volunteers: No

Summary:

      Phase III Metastatic Pancreatic Cancer
    

Eligibility criteria:

        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.