Study of Gemcitabine, Abraxane® Plus Placebo Versus Gemcitabine, Abraxane® Plus 1 or 2 Truncated Courses of Demcizumab in Subjects With 1st-Line Metastatic Pancreatic Ductal Adenocarcinoma
Condition: Pancreatic Cancer
MeSH terms: Adenocarcinoma
Intervention: Demcizumab; Abraxane®; gemcitabine; Placebo
Intervention description: administered intravenously; administered intravenously; administered intravenously
Intervention MeSH terms: Gemcitabine; Albumin-Bound Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 207.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: No
Keywords: 1st-line metastatic pancreatic ductal adenocarcinoma

Summary:

      This is a randomized, double blind, 3 arm (1:1:1) study in subjects with 1st-line metastatic
      pancreatic ductal adenocarcinoma.

      The purpose is to test the efficacy and safety of demcizumab, when given in combination with
      gemcitabine and Abraxane® compared to placebo. The administration of gemcitabine and
      Abraxane® is a standard treatment for patients with metastatic pancreatic ductal
      adenocarcinoma.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects must have histologically confirmed metastatic pancreatic ductal
             adenocarcinoma.. Prior chemotherapy and/or radiotherapy either in the adjuvant or
             neoadjuvant setting or for metastatic disease is not allowed.

          2. Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue (from either the
             primary tumor, locoregional disease or a metastatic site), either fresh
             core-needle-biopsied or archived (two FFPE cores preferred whenever possible). If
             fresh tissue is obtained, the core biopsy must be done at least 7 days prior to
             randomization.

          3. Age ≥21 years

          4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 5. Measurable
             disease per RECIST v1.1

          5. Adequate organ and marrow function

          6. Signed Informed Consent Form

          7. For women of childbearing potential, agreement to use two effective forms of
             contraception

        Exclusion Criteria:

          1. Subjects with a neuroendocrine tumor of the pancreas, an acinar tumor of the pancreas
             or a pancreatic tumor with mixed histologies.

          2. Subjects receiving heparin, warfarin, factor Xa inhibitors or other similar
             anticoagulants. Note: Subjects may be receiving low-dose aspirin and/or non-steroidal
             anti-inflammatory agents.

          3. Subjects with brain metastases, leptomeningeal disease, uncontrolled seizure disorder,
             or active neurologic disease

          4. Subjects with Grade >2 peripheral neuropathy

          5. Subjects with clinically significant ascites

          6. Malignancies other than pancreatic cancer successfully treated within 3 years prior to
             randomization, except for adequately treated carcinoma in situ of the cervix, basal or
             squamous cell skin cancer, treated superficial bladder cancer, localized prostate
             cancer treated surgically with curative intent, ductal carcinoma in situ treated
             surgically with curative intent

          7. Significant intercurrent illness that will limit the patient's ability to participate
             in the study or may result in their death over the next 18 months

          8. History of a significant allergic reaction attributed to humanized or human monoclonal
             antibody therapy

          9. Subjects with known clinically significant gastrointestinal disease including, but not
             limited to, inflammatory bowel disease

         10. Pregnant women or nursing women

         11. Subjects with known HIV infection

         12. Known bleeding disorder or coagulopathy