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
- Conditions
- Nonsquamous Nonsmall Cell Neoplasm of Lung
- Interventions
- Registration Number
- NCT02259582
- Lead Sponsor
- OncoMed Pharmaceuticals, Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 82
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 3 pem, carbo, dem x 4 cycles, dem retreatment Carboplatin 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 Arm 1 Pem, carbo, placebo x 4 cycles Pemetrexed 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 3 pem, carbo, dem x 4 cycles, dem retreatment Pemetrexed 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 Arm 1 Pem, carbo, placebo x 4 cycles Carboplatin 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 2 Pem, carbo x 4 cycles, one course of dem Carboplatin 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 2 Pem, carbo x 4 cycles, one course of dem Pemetrexed 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 3 pem, carbo, dem x 4 cycles, dem retreatment demcizumab 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 Arm 2 Pem, carbo x 4 cycles, one course of dem demcizumab 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
- Primary Outcome Measures
Name Time Method To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms. 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. 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
Name Time Method
Trial Locations
- Locations (43)
Centre Hospitalier Jolimont-Lobbes
🇧🇪La Louviere, Belgium
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Gabrail Cancer Center Research
🇺🇸Canton, Ohio, United States
Ziekenhuisnetwerk Antwerpen- Koningin Paola Kinderzickenhuis
🇧🇪Antwerpen, Belgium
CHR de Ia Citadelle
🇧🇪Liege, Belgium
Desert Hematology Oncology Medical Group, Inc.
🇺🇸Rancho Mirage, California, United States
Ocala Oncology Center
🇺🇸Ocala, Florida, United States
Smilow Cancer Hospital at Yale-New Haven
🇮🇹Aviano, Pordenone, Italy
Edward H. Kaplan MD & Associates
🇺🇸Skokie, Illinois, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Anne Arundel Medical Center
🇺🇸Annapolis, Maryland, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Broome Oncology, LLC
🇺🇸Binghamton, New York, United States
Hematology Oncology Associates of Rockland
🇺🇸Nyack, New York, United States
Gaston Hematology & Oncology
🇺🇸Gastonia, North Carolina, United States
Texas Oncology-Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Texas Oncology-Sherman
🇺🇸Sherman, Texas, United States
Compass Oncology
🇺🇸Vancouver, Washington, United States
Chris O'Brien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
University of Texas Medical Branch at Galveston
🇺🇸Galveston, Texas, United States
North Coast Cancer Institute Port Macquarie Base Hospital
🇦🇺Port Macquarie, New South Wales, Australia
The Kinghorn Cancer Centre
🇦🇺Darlinghurst, New South Wales, Australia
Royall Brisbane & Women's Hospital
🇦🇺Herston, Queensland, Australia
The Queen Elizabeth Hospital
🇦🇺Woodville South, South Australia, Australia
Icon Cancer Foundation
🇦🇺Milton, Queensland, Australia
Monash Health, Monash Cancer Centre-Moorabbin
🇦🇺Bentleigh East, Victoria, Australia
St. John of God Subiaco Hospital
🇦🇺Subiaco, Western Australia, Australia
Hospital Universitari Germans Trias i Pujol
🇪🇸Barcelona, Spain
Azienda Ospedaliera Città della Salute e della Scienza di Torino
🇮🇹Torino, Piemonte, Italy
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Toscana, Italy
Hospital Puerta de Hierro Majadahonda
🇪🇸Majadahonda, Madrid, Spain
Azienda Ospedaliera Istituti Ospitalieri
🇮🇹Cremona, Lombardia, Italy
Hospital Nuestra Senora de Sonsoles
🇪🇸Avila, Spain
Hospital Universitari Vall D'Hebron
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Institute Catalan de Oncologia (ICO L'Hospitalet)
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Madrid Universitario Sanchinarro
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Grand Hopital de Charleroi- Site Notre-Dame
🇧🇪Charleroi, Belgium
University Hospitals of Cleveland
🇺🇸Cleveland, Ohio, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States