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)

September 7, 2020 updated by: OncoMed Pharmaceuticals, Inc.

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

82

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Chris O'Brien Lifehouse
      • Darlinghurst, New South Wales, Australia, 2010
        • The Kinghorn Cancer Centre
      • Port Macquarie, New South Wales, Australia, 2444
        • North Coast Cancer Institute Port Macquarie Base Hospital
    • Queensland
      • Herston, Queensland, Australia, 4029
        • Royall Brisbane & Women's Hospital
      • Milton, Queensland, Australia, 4064
        • Icon Cancer Foundation
    • South Australia
      • Woodville South, South Australia, Australia, 5011
        • The Queen Elizabeth Hospital
    • Victoria
      • Bentleigh East, Victoria, Australia, 3165
        • Monash Health, Monash Cancer Centre-Moorabbin
    • Western Australia
      • Subiaco, Western Australia, Australia, 6008
        • St. John of God Subiaco Hospital
  • Belgium
      • Antwerpen, Belgium, 2020
        • Ziekenhuisnetwerk Antwerpen- Koningin Paola Kinderzickenhuis
      • Charleroi, Belgium, 6000
        • Grand Hopital de Charleroi- Site Notre-Dame
      • La Louviere, Belgium, 7100
        • Centre Hospitalier Jolimont-Lobbes
      • Liege, Belgium, 4000
        • CHR de Ia Citadelle
  • Italy
    • Lombardia
      • Cremona, Lombardia, Italy, 26100
        • Azienda Ospedaliera Istituti Ospitalieri
    • Piemonte
      • Torino, Piemonte, Italy, 10126
        • Azienda Ospedaliera Città della Salute e della Scienza di Torino
    • Pordenone
      • Aviano, Pordenone, Italy, 33081
        • Smilow Cancer Hospital at Yale-New Haven
    • Toscana
      • Pisa, Toscana, Italy, 56126
        • Azienda Ospedaliero Universitaria Pisana
  • Spain
      • Avila, Spain, 05004
        • Hospital Nuestra Señora de Sonsoles
      • Barcelona, Spain, 08036
        • Hospital Clinic De Barcelona
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
      • Barcelona, Spain, 08916
        • Hospital Universitari Germans Trias i Pujol
      • Barcelona, Spain, 08908
        • Institute Catalan de Oncologia (ICO L'Hospitalet)
      • Madrid, Spain, 28040
        • Hospital Clinico San Carlos
      • Madrid, Spain, 28050
        • Hospital Madrid Universitario Sanchinarro
      • Madrid, Spain, 28009
        • Hospital General Universitario Gregorio Marañon
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio
    • Barcelona
      • Badalona, Barcelona, Spain, 08916
        • Hospital Universitari Germans Trias i Pujol
    • Madrid
      • Majadahonda, Madrid, Spain, 28222
        • Hospital Puerta de Hierro Majadahonda
  • United States
    • California
      • Rancho Mirage, California, United States, 92270
        • Desert Hematology Oncology Medical Group, Inc.
      • San Francisco, California, United States, . 94143-1705
        • University of California, San Francisco
    • Connecticut
      • New Haven, Connecticut, United States, 06510-3221
        • Smilow Cancer Hospital at Yale-New Haven
    • Florida
      • Ocala, Florida, United States, 34471
        • Ocala Oncology Center
    • Illinois
      • Skokie, Illinois, United States, 60076
        • Edward H. Kaplan MD & Associates
    • Maryland
      • Annapolis, Maryland, United States, 21401
        • Anne Arundel Medical Center
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
      • Detroit, Michigan, United States, 4820I
        • Karmanos Cancer Institute
    • New York
      • Binghamton, New York, United States, 13905
        • Broome Oncology, LLC
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • Nyack, New York, United States, 10960
        • Hematology Oncology Associates of Rockland
    • North Carolina
      • Gastonia, North Carolina, United States, 28054
        • Gaston Hematology & Oncology
    • Ohio
      • Canton, Ohio, United States, 44718
        • Gabrail Cancer Center Research
      • Cleveland, Ohio, United States, 44106
        • University Hospitals of Cleveland
    • Texas
      • Dallas, Texas, United States, 75246
        • Texas Oncology-Baylor Charles A. Sammons Cancer Center
      • Galveston, Texas, United States, 77555
        • University of Texas Medical Branch at Galveston
      • Sherman, Texas, United States, 75090-0504
        • Texas Oncology-Sherman
    • Washington
      • Vancouver, Washington, United States, 98684
        • Compass Oncology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Main Inclusion Criteria:

  1. Signed Informed Consent Form
  2. Histologically or cytologically confirmed Stage IV non-squamous NSCLC
  3. Availability of FFPE (formalin-fixed paraffin-embedded) tumor tissue, either fresh core-needle-biopsied or archived
  4. Age > or = to 21 years
  5. ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1
  6. Disease that is measurable per RECIST v1.1
  7. Adequate organ and marrow function
  8. For women of childbearing potential, agreement to use two effective forms of contraception

Main Exclusion Criteria:

  1. Histologically or cytologically documented, advanced, mixed non-small cell and small cell tumors or mixed adenosquamous carcinomas
  2. 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])
  3. 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
  4. Evidence of tumor invading major blood vessels, cavitation of one or more pulmonary tumor mass(es) or tracheo-esophageal fistula
  5. Brain metastases, leptomeningeal disease, uncontrolled seizure disorder, or active neurologic disease
  6. Malignancies other than non-squamous NSCLC successfully treated within 3 years prior to randomization (with the exception of certain early-stage cancers)
  7. History of a significant allergic reaction attributed to humanized or human monoclonal antibody therapy
  8. 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
  9. Recent hemoptysis >2.5 mL or serious bleeding from another site, known bleeding disorder or coagulopathy or therapeutic anti-coagulation
  10. 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Arm 1 Pem, carbo, placebo x 4 cycles
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
Drug: Pemetrexed
Drug: Carboplatin
Active Comparator: Arm 2 Pem, carbo x 4 cycles, one course of dem
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
Drug: Pemetrexed
Drug: Carboplatin
Drug: demcizumab
Active Comparator: Arm 3 pem, carbo, dem x 4 cycles, dem retreatment
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
Drug: Pemetrexed
Drug: Carboplatin
Drug: demcizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms.
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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

OncoMed Pharmaceuticals, Inc.

Collaborators

Celgene Corporation

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2015

Primary Completion (Actual)

April 7, 2017

Study Completion (Actual)

April 7, 2017

Study Registration Dates

First Submitted

September 17, 2014

First Submitted That Met QC Criteria

October 3, 2014

First Posted (Estimate)

October 8, 2014

Study Record Updates

Last Update Posted (Actual)

September 9, 2020

Last Update Submitted That Met QC Criteria

September 7, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M18-007

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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