A Study of Carboplatin, Pemetrexed Plus Placebo vs Carboplatin, Pemetrexed Plus 1 or 2 Truncated Courses of Demcizumab in Subjects With Non-Squamous Non-Small Cell Lung Cancer
DENALI
A 2-Arm Phase 2 Double-Blind Randomized Study of Carboplatin, Pemetrexed Plus Placebo Versus Carboplatin, Pemetrexed Plus Truncated Demcizumab as First-Line Treatment in Subjects With Stage IV Non-Squamous Non-Small Cell Lung Cancer
1 other identifier
interventional
82
5 countries
45
Brief Summary
A randomized, double-blind, 3-arm (1:1:1) study in subjects with first-line Stage IV non-squamous NSCLC. The purpose is to test the efficacy and safety of demcizumab, when given in combination with carboplatin and pemetrexed compared to placebo. The administration of carboplatin and pemetrexed is a standard treatment for patients with non-squamous non-small cell lung cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Feb 2015
45 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 17, 2014
CompletedFirst Posted
Study publicly available on registry
October 8, 2014
CompletedStudy Start
First participant enrolled
February 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 7, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
April 7, 2017
CompletedResults Posted
Study results publicly available
August 20, 2018
CompletedSeptember 9, 2020
September 1, 2020
2.2 years
September 17, 2014
May 21, 2018
September 7, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms.
Investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 response rate (unconfirmed) in placebo/placebo arm to demcizumab/placebo arm and demcizumab/demcizumab arm combined in subjects with first-line stage IV non-small cell lung cancer (NSCLC). Response rate was based on Investigator-assessed best-overall-response (BOR) and was defined as the best unconfirmed response determined by RECIST version 1.1 recorded from the start of the treatment until disease progression in the following order of importance: CR, PR , SD, progressive disease (PD), not evaluable, or missing.
Response assessment data was collected until the subject started alternative anti-cancer treatment or developed progressive disease, whichever occurred first, assessed up to approximately 26 months.
Study Arms (3)
Arm 1 Pem, carbo, placebo x 4 cycles
PLACEBO COMPARATORPemetrexed (500 mg/m2),carboplatin (area under the concentration-time curve of 6 mg/mL x min) once every 21 days X 4 cycles, pemetrexed maintenance and placebo starting at Day 84
Arm 2 Pem, carbo x 4 cycles, one course of dem
ACTIVE COMPARATORPemetrexed (500 mg/m2), carboplatin (area under the concentration-time curve of 6 mg/mL x min) x 4 cycles, one course of demcizumab 5mg/kg, maintenance pemetrexed + placebo starting on Day 84
Arm 3 pem, carbo, dem x 4 cycles, dem retreatment
ACTIVE COMPARATORPemetrexed (500 mg/m2), carboplatin (area under the concentration-time curve of 6 mg/mL x min) x 4 cycles, maintenance pemetrexed starting on Day 84. 2 courses of demcizumab 5 mg/kg
Interventions
Eligibility Criteria
You may qualify if:
- Signed Informed Consent Form
- Histologically or cytologically confirmed Stage IV non-squamous NSCLC
- Availability of FFPE (formalin-fixed paraffin-embedded) tumor tissue, either fresh core-needle-biopsied or archived
- Age \> or = to 21 years
- ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1
- Disease that is measurable per RECIST v1.1
- Adequate organ and marrow function
- For women of childbearing potential, agreement to use two effective forms of contraception
You may not qualify if:
- Histologically or cytologically documented, advanced, mixed non-small cell and small cell tumors or mixed adenosquamous carcinomas
- NSCLC with known EGFR (epidermal growth factor receptor ) mutation or anaplastic lymphoma kinase (ALK) gene translocation (such as EML4 \[echinoderm microtubule-associated protein-like 4\]-ALK \[anaplastic lymphoma kinase\])
- Prior or ongoing therapy (including chemotherapy, antibody therapy, tyrosine kinase inhibitors, radiotherapy, immunotherapy, hormonal therapy, or investigational therapy) for the treatment of Stage IV non-squamous NSCLC
- Evidence of tumor invading major blood vessels, cavitation of one or more pulmonary tumor mass(es) or tracheo-esophageal fistula
- Brain metastases, leptomeningeal disease, uncontrolled seizure disorder, or active neurologic disease
- Malignancies other than non-squamous NSCLC successfully treated within 3 years prior to randomization (with the exception of certain early-stage cancers)
- History of a significant allergic reaction attributed to humanized or human monoclonal antibody therapy
- Significant intercurrent illness defined as an illness that may result in the subject's death prior to their death from non-squamous NSCLC and/or significantly limit their ability to comply with the requirements of this study
- Recent hemoptysis \>2.5 mL or serious bleeding from another site, known bleeding disorder or coagulopathy or therapeutic anti-coagulation
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization, or anticipation of need for major surgical procedure during the course of the study
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- OncoMed Pharmaceuticals, Inc.lead
- Celgene Corporationcollaborator
Study Sites (45)
Desert Hematology Oncology Medical Group, Inc.
Rancho Mirage, California, 92270, United States
University of California, San Francisco
San Francisco, California, . 94143-1705, United States
Smilow Cancer Hospital at Yale-New Haven
New Haven, Connecticut, 06510-3221, United States
Ocala Oncology Center
Ocala, Florida, 34471, United States
Edward H. Kaplan MD & Associates
Skokie, Illinois, 60076, United States
Anne Arundel Medical Center
Annapolis, Maryland, 21401, United States
Henry Ford Health System
Detroit, Michigan, 48202, United States
Karmanos Cancer Institute
Detroit, Michigan, 4820I, United States
Broome Oncology, LLC
Binghamton, New York, 13905, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Hematology Oncology Associates of Rockland
Nyack, New York, 10960, United States
Gaston Hematology & Oncology
Gastonia, North Carolina, 28054, United States
Gabrail Cancer Center Research
Canton, Ohio, 44718, United States
University Hospitals of Cleveland
Cleveland, Ohio, 44106, United States
Texas Oncology-Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246, United States
University of Texas Medical Branch at Galveston
Galveston, Texas, 77555, United States
Texas Oncology-Sherman
Sherman, Texas, 75090-0504, United States
Compass Oncology
Vancouver, Washington, 98684, United States
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050, Australia
The Kinghorn Cancer Centre
Darlinghurst, New South Wales, 2010, Australia
North Coast Cancer Institute Port Macquarie Base Hospital
Port Macquarie, New South Wales, 2444, Australia
Royall Brisbane & Women's Hospital
Herston, Queensland, 4029, Australia
Icon Cancer Foundation
Milton, Queensland, 4064, Australia
The Queen Elizabeth Hospital
Woodville South, South Australia, 5011, Australia
Monash Health, Monash Cancer Centre-Moorabbin
Bentleigh East, Victoria, 3165, Australia
St. John of God Subiaco Hospital
Subiaco, Western Australia, 6008, Australia
Ziekenhuisnetwerk Antwerpen- Koningin Paola Kinderzickenhuis
Antwerp, 2020, Belgium
Grand Hopital de Charleroi- Site Notre-Dame
Charleroi, 6000, Belgium
Centre Hospitalier Jolimont-Lobbes
La Louvière, 7100, Belgium
CHR de Ia Citadelle
Liège, 4000, Belgium
Azienda Ospedaliera Istituti Ospitalieri
Cremona, Lombardy, 26100, Italy
Azienda Ospedaliera Città della Salute e della Scienza di Torino
Turin, Piedmont, 10126, Italy
Smilow Cancer Hospital at Yale-New Haven
Aviano, Pordenone, 33081, Italy
Azienda Ospedaliero Universitaria Pisana
Pisa, Tuscany, 56126, Italy
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, 08916, Spain
Hospital Puerta de Hierro Majadahonda
Majadahonda, Madrid, 28222, Spain
Hospital Nuestra Senora de Sonsoles
Ávila, 05004, Spain
Hospital Universitari Vall D'Hebron
Barcelona, 08035, Spain
Hospital Clinic de Barcelona
Barcelona, 08036, Spain
Institute Catalan de Oncologia (ICO L'Hospitalet)
Barcelona, 08908, Spain
Hospital Universitari Germans Trias i Pujol
Barcelona, 08916, Spain
Hospital General Universitario Gregorio Marañon
Madrid, 28009, Spain
Hospital Clinico San Carlos
Madrid, 28040, Spain
Hospital Madrid Universitario Sanchinarro
Madrid, 28050, Spain
Hospital Universitario Virgen del Rocio
Seville, 41013, Spain
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Manager, Regulatory Affairs
- Organization
- OncoMed Pharmaceuticals, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 17, 2014
First Posted
October 8, 2014
Study Start
February 1, 2015
Primary Completion
April 7, 2017
Study Completion
April 7, 2017
Last Updated
September 9, 2020
Results First Posted
August 20, 2018
Record last verified: 2020-09