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

Study Overview
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Brief Summary
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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.

Official Title
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A 3-Arm Phase 2 Double-Blind Randomized 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

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Demcizumab
* Drug: Abraxane®
* Drug: gemcitabine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. 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. Age ≥21 years Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 5. Measurable disease per RECIST v1.1 Adequate organ and marrow function Signed Informed Consent Form For women of childbearing potential, agreement to use two effective forms of contraception Exclusion Criteria: Subjects with a neuroendocrine tumor of the pancreas, an acinar tumor of the pancreas or a pancreatic tumor with mixed histologies. 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. Subjects with brain metastases, leptomeningeal disease, uncontrolled seizure disorder, or active neurologic disease Subjects with Grade >2 peripheral neuropathy Subjects with clinically significant ascites 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 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 History of a significant allergic reaction attributed to humanized or human monoclonal antibody therapy Subjects with known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease Pregnant women or nursing women Subjects with known HIV infection Known bleeding disorder or coagulopathy

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abraxane® and gemcitabine plus placebo<br>Abraxane® and gemcitabine plus placebo (3 cycles), Abraxane® and gemcitabine (3 cycles), Abraxane® and gemcitabine plus placebo (3 cycles) and then Abraxane® and gemcitabine until disease progression | Drug: Demcizumab<br>* administered intravenously<br>Drug: Abraxane®<br>* administered intravenously<br>Drug: gemcitabine<br>* administered intravenously<br>Drug: Placebo<br> <br> |
| Experimental: Abraxane® and gemcitabine plus demcizumab plus placebo<br>Abraxane® and gemcitabine plus demcizumab (3 cycles), Abraxane® and gemcitabine (3 cycles), Abraxane® and gemcitabine plus placebo (3 cycles) and then Abraxane® and gemcitabine until disease progression | Drug: Demcizumab<br>* administered intravenously<br>Drug: Abraxane®<br>* administered intravenously<br>Drug: gemcitabine<br>* administered intravenously<br>|
| Experimental: Abraxane® and gemcitabine plus demcizumab<br>Abraxane® and gemcitabine plus demcizumab (3 cycles), Abraxane® and gemcitabine (3 cycles), Abraxane® and gemcitabine plus demcizumab (3 cycles) and then Abraxane® and gemcitabine until disease progression | Drug: Demcizumab<br>* administered intravenously<br>Drug: Abraxane®<br>* administered intravenously<br>Drug: gemcitabine<br>* administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hazard of Progression in the Placebo/Placebo Arm and the Pooled Demcizumab Arms | Investigator assessed Kaplan-Meier estimates of progression-free survival for placebo/placebo arm and pooled demcizumab arm. | Investigator-assessed progression-free survival time through duration of the study (2 years, 23 days). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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1st-line metastatic pancreatic ductal adenocarcinoma