Back to resultsA 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)
Primary Purpose
Nonsquamous Nonsmall Cell Neoplasm of Lung
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Pemetrexed
Carboplatin
demcizumab
Sponsored by
About this trial
This is an interventional treatment trial for Nonsquamous Nonsmall Cell Neoplasm of Lung focused on measuring Phase 2, histologically, confirmed, malignancy, metastatic, pemetrexed, carboplatin, carcinoma, non small cell lung, lung neoplasms, lung diseases
Eligibility Criteria
Main Inclusion Criteria:
- 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
Main Exclusion Criteria:
- 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
Sites / Locations
- Desert Hematology Oncology Medical Group, Inc.
- University of California, San Francisco
- Smilow Cancer Hospital at Yale-New Haven
- Ocala Oncology Center
- Edward H. Kaplan MD & Associates
- Anne Arundel Medical Center
- Henry Ford Health System
- Karmanos Cancer Institute
- Broome Oncology, LLC
- Roswell Park Cancer Institute
- Hematology Oncology Associates of Rockland
- Gaston Hematology & Oncology
- Gabrail Cancer Center Research
- University Hospitals of Cleveland
- Texas Oncology-Baylor Charles A. Sammons Cancer Center
- University of Texas Medical Branch at Galveston
- Texas Oncology-Sherman
- Compass Oncology
- Chris O'Brien Lifehouse
- The Kinghorn Cancer Centre
- North Coast Cancer Institute Port Macquarie Base Hospital
- Royall Brisbane & Women's Hospital
- Icon Cancer Foundation
- The Queen Elizabeth Hospital
- Monash Health, Monash Cancer Centre-Moorabbin
- St. John of God Subiaco Hospital
- Ziekenhuisnetwerk Antwerpen- Koningin Paola Kinderzickenhuis
- Grand Hopital de Charleroi- Site Notre-Dame
- Centre Hospitalier Jolimont-Lobbes
- CHR de Ia Citadelle
- Azienda Ospedaliera Istituti Ospitalieri
- Azienda Ospedaliera Città della Salute e della Scienza di Torino
- Smilow Cancer Hospital at Yale-New Haven
- Azienda Ospedaliero Universitaria Pisana
- Hospital Universitari Germans Trias i Pujol
- Hospital Puerta de Hierro Majadahonda
- Hospital Nuestra Senora de Sonsoles
- Hospital Universitari Vall D'Hebron
- Hospital Clinic de Barcelona
- Institute Catalan de Oncologia (ICO L'Hospitalet)
- Hospital Universitari Germans Trias i Pujol
- Hospital General Universitario Gregorio Marañon
- Hospital Clinico San Carlos
- Hospital Madrid Universitario Sanchinarro
- Hospital Universitario Virgen del Rocio
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Active Comparator
Active Comparator
Arm Label
Arm 1 Pem, carbo, placebo x 4 cycles
Arm 2 Pem, carbo x 4 cycles, one course of dem
Arm 3 pem, carbo, dem x 4 cycles, dem retreatment
Arm Description
Pemetrexed (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
Pemetrexed (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
Pemetrexed (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
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT02259582
First Posted
September 17, 2014
Last Updated
September 7, 2020
Sponsor
OncoMed Pharmaceuticals, Inc.
Collaborators
Celgene Corporation
1. Study Identification
Unique Protocol Identification Number
NCT02259582
Brief Title
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
Acronym
DENALI
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
February 2015 (Actual)
Primary Completion Date
April 7, 2017 (Actual)
Study Completion Date
April 7, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
OncoMed Pharmaceuticals, Inc.
Collaborators
Celgene Corporation
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed Description
Patients will be enrolled at centers in North America, Western Europe, Australia and New Zealand. Up to 28 days (4 weeks) prior to treatment.
If enrolled in the study, you will receive intravenous (in the vein) infusions of demcizumab (or placebo), carboplatin, and pemetrexed administered on the same day, every 21 days for 4 cycles, or until it has been shown that your cancer has gotten worse. If your physician decides to delay treatment with one of the agents due to side effects, the other agents may still be administered as scheduled. After 4 cycles, if you have stable or improved disease, you will continue to receive pemetrexed once every 21 days as maintenance therapy. After 8 cycles, if you have stable or improved disease, you may receive demcizumab (or placebo), every 21 days for 4 more cycles.
You will undergo assessments every 6 weeks to determine the status of your disease.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nonsquamous Nonsmall Cell Neoplasm of Lung
Keywords
Phase 2, histologically, confirmed, malignancy, metastatic, pemetrexed, carboplatin, carcinoma, non small cell lung, lung neoplasms, lung diseases
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
82 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1 Pem, carbo, placebo x 4 cycles
Arm Type
Placebo Comparator
Arm Description
Pemetrexed (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 Title
Arm 2 Pem, carbo x 4 cycles, one course of dem
Arm Type
Active Comparator
Arm Description
Pemetrexed (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 Title
Arm 3 pem, carbo, dem x 4 cycles, dem retreatment
Arm Type
Active Comparator
Arm Description
Pemetrexed (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
Intervention Type
Drug
Intervention Name(s)
Pemetrexed
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Type
Drug
Intervention Name(s)
demcizumab
Primary Outcome Measure Information:
Title
To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms.
Description
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.
Time Frame
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Main Inclusion Criteria:
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
Main Exclusion Criteria:
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
Facility Information:
Facility Name
Desert Hematology Oncology Medical Group, Inc.
City
Rancho Mirage
State/Province
California
ZIP/Postal Code
92270
Country
United States
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
. 94143-1705
Country
United States
Facility Name
Smilow Cancer Hospital at Yale-New Haven
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510-3221
Country
United States
Facility Name
Ocala Oncology Center
City
Ocala
State/Province
Florida
ZIP/Postal Code
34471
Country
United States
Facility Name
Edward H. Kaplan MD & Associates
City
Skokie
State/Province
Illinois
ZIP/Postal Code
60076
Country
United States
Facility Name
Anne Arundel Medical Center
City
Annapolis
State/Province
Maryland
ZIP/Postal Code
21401
Country
United States
Facility Name
Henry Ford Health System
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
4820I
Country
United States
Facility Name
Broome Oncology, LLC
City
Binghamton
State/Province
New York
ZIP/Postal Code
13905
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Hematology Oncology Associates of Rockland
City
Nyack
State/Province
New York
ZIP/Postal Code
10960
Country
United States
Facility Name
Gaston Hematology & Oncology
City
Gastonia
State/Province
North Carolina
ZIP/Postal Code
28054
Country
United States
Facility Name
Gabrail Cancer Center Research
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Facility Name
University Hospitals of Cleveland
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Texas Oncology-Baylor Charles A. Sammons Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
University of Texas Medical Branch at Galveston
City
Galveston
State/Province
Texas
ZIP/Postal Code
77555
Country
United States
Facility Name
Texas Oncology-Sherman
City
Sherman
State/Province
Texas
ZIP/Postal Code
75090-0504
Country
United States
Facility Name
Compass Oncology
City
Vancouver
State/Province
Washington
ZIP/Postal Code
98684
Country
United States
Facility Name
Chris O'Brien Lifehouse
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
The Kinghorn Cancer Centre
City
Darlinghurst
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
North Coast Cancer Institute Port Macquarie Base Hospital
City
Port Macquarie
State/Province
New South Wales
ZIP/Postal Code
2444
Country
Australia
Facility Name
Royall Brisbane & Women's Hospital
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
Icon Cancer Foundation
City
Milton
State/Province
Queensland
ZIP/Postal Code
4064
Country
Australia
Facility Name
The Queen Elizabeth Hospital
City
Woodville South
State/Province
South Australia
ZIP/Postal Code
5011
Country
Australia
Facility Name
Monash Health, Monash Cancer Centre-Moorabbin
City
Bentleigh East
State/Province
Victoria
ZIP/Postal Code
3165
Country
Australia
Facility Name
St. John of God Subiaco Hospital
City
Subiaco
State/Province
Western Australia
ZIP/Postal Code
6008
Country
Australia
Facility Name
Ziekenhuisnetwerk Antwerpen- Koningin Paola Kinderzickenhuis
City
Antwerpen
ZIP/Postal Code
2020
Country
Belgium
Facility Name
Grand Hopital de Charleroi- Site Notre-Dame
City
Charleroi
ZIP/Postal Code
6000
Country
Belgium
Facility Name
Centre Hospitalier Jolimont-Lobbes
City
La Louviere
ZIP/Postal Code
7100
Country
Belgium
Facility Name
CHR de Ia Citadelle
City
Liege
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Azienda Ospedaliera Istituti Ospitalieri
City
Cremona
State/Province
Lombardia
ZIP/Postal Code
26100
Country
Italy
Facility Name
Azienda Ospedaliera Città della Salute e della Scienza di Torino
City
Torino
State/Province
Piemonte
ZIP/Postal Code
10126
Country
Italy
Facility Name
Smilow Cancer Hospital at Yale-New Haven
City
Aviano
State/Province
Pordenone
ZIP/Postal Code
33081
Country
Italy
Facility Name
Azienda Ospedaliero Universitaria Pisana
City
Pisa
State/Province
Toscana
ZIP/Postal Code
56126
Country
Italy
Facility Name
Hospital Universitari Germans Trias i Pujol
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Hospital Puerta de Hierro Majadahonda
City
Majadahonda
State/Province
Madrid
ZIP/Postal Code
28222
Country
Spain
Facility Name
Hospital Nuestra Senora de Sonsoles
City
Avila
ZIP/Postal Code
05004
Country
Spain
Facility Name
Hospital Universitari Vall D'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clinic de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Institute Catalan de Oncologia (ICO L'Hospitalet)
City
Barcelona
ZIP/Postal Code
08908
Country
Spain
Facility Name
Hospital Universitari Germans Trias i Pujol
City
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Hospital General Universitario Gregorio Marañon
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Facility Name
Hospital Clinico San Carlos
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Hospital Madrid Universitario Sanchinarro
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocio
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
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
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