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 (YOSEMITE)

Study Description

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Brief 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.

Condition or disease	Intervention/treatment	Phase
Pancreatic Cancer	Drug: Demcizumab; Drug: Abraxane®; Drug: gemcitabine; Drug: Placebo	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	207 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	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
Actual Study Start Date :	April 20, 2015
Actual Primary Completion Date :	May 2017
Actual Study Completion Date :	September 2017

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Abraxane® and gemcitabine plus placebo; 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; administered intravenously; Drug: Abraxane®; administered intravenously; Drug: gemcitabine; administered intravenously; Drug: Placebo
Experimental: Abraxane® and gemcitabine plus demcizumab plus placebo; 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; administered intravenously; Drug: Abraxane®; administered intravenously; Drug: gemcitabine; administered intravenously
Experimental: Abraxane® and gemcitabine plus demcizumab; 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; administered intravenously; Drug: Abraxane®; administered intravenously; Drug: gemcitabine; administered intravenously

Outcome Measures

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Primary Outcome Measures :

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

Eligibility Criteria

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Ages Eligible for Study:	21 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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  Show 42 Study Locations

Sponsors and Collaborators

OncoMed Pharmaceuticals, Inc.

Celgene Corporation

  Study Documents (Full-Text)

Documents provided by OncoMed Pharmaceuticals, Inc.:

Statistical Analysis Plan  [PDF] March 8, 2017

Study Protocol and Informed Consent Form  [PDF] December 19, 2016

More Information

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Responsible Party:	OncoMed Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT02289898 History of Changes
Other Study ID Numbers:	M18-006
First Posted:	November 13, 2014
Results First Posted:	August 8, 2018
Last Update Posted:	August 8, 2018
Last Verified:	July 2018

Keywords provided by OncoMed Pharmaceuticals, Inc.:

1st-line metastatic pancreatic ductal adenocarcinoma

Additional relevant MeSH terms:

Adenocarcinoma; Pancreatic Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Gemcitabine; Albumin-Bound Paclitaxel; Paclitaxel	Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents, Phytogenic; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators