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

Nonsquamous Nonsmall Cell Neoplasm of Lung Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02259582
• Other study ID #: M18-007
• Status: Completed
• Phase: Phase 2
• Start date: February 2015
• Est. completion date: April 7, 2017

Study information

• Verified date: September 2020
• Source: Mereo BioPharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: April 7, 2017
• Est. primary completion date: April 7, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Neoplasms
• Nonsquamous Nonsmall Cell Neoplasm of Lung

Intervention

Drug:
• Pemetrexed

• Carboplatin

• demcizumab

Locations

Country	Name	City	State
Australia	Monash Health, Monash Cancer Centre-Moorabbin	Bentleigh East	Victoria
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	The Kinghorn Cancer Centre	Darlinghurst	New South Wales
Australia	Royall Brisbane & Women's Hospital	Herston	Queensland
Australia	Icon Cancer Foundation	Milton	Queensland
Australia	North Coast Cancer Institute Port Macquarie Base Hospital	Port Macquarie	New South Wales
Australia	St. John of God Subiaco Hospital	Subiaco	Western Australia
Australia	The Queen Elizabeth Hospital	Woodville South	South Australia
Belgium	Ziekenhuisnetwerk Antwerpen- Koningin Paola Kinderzickenhuis	Antwerpen
Belgium	Grand Hopital de Charleroi- Site Notre-Dame	Charleroi
Belgium	Centre Hospitalier Jolimont-Lobbes	La Louviere
Belgium	CHR de Ia Citadelle	Liege
Italy	Smilow Cancer Hospital at Yale-New Haven	Aviano	Pordenone
Italy	Azienda Ospedaliera Istituti Ospitalieri	Cremona	Lombardia
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa	Toscana
Italy	Azienda Ospedaliera Città della Salute e della Scienza di Torino	Torino	Piemonte
Spain	Hospital Nuestra Senora de Sonsoles	Avila
Spain	Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitari Germans Trias i Pujol	Barcelona
Spain	Hospital Universitari Vall D'Hebron	Barcelona
Spain	Institute Catalan de Oncologia (ICO L'Hospitalet)	Barcelona
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Madrid Universitario Sanchinarro	Madrid
Spain	Hospital Puerta de Hierro Majadahonda	Majadahonda	Madrid
Spain	Hospital Universitario Virgen del Rocio	Sevilla
United States	Anne Arundel Medical Center	Annapolis	Maryland
United States	Broome Oncology, LLC	Binghamton	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	University of Texas Medical Branch at Galveston	Galveston	Texas
United States	Gaston Hematology & Oncology	Gastonia	North Carolina
United States	Smilow Cancer Hospital at Yale-New Haven	New Haven	Connecticut
United States	Hematology Oncology Associates of Rockland	Nyack	New York
United States	Ocala Oncology Center	Ocala	Florida
United States	Desert Hematology Oncology Medical Group, Inc.	Rancho Mirage	California
United States	University of California, San Francisco	San Francisco	California
United States	Texas Oncology-Sherman	Sherman	Texas
United States	Edward H. Kaplan MD & Associates	Skokie	Illinois
United States	Compass Oncology	Vancouver	Washington

Sponsors (2)

Lead Sponsor	Collaborator
OncoMed Pharmaceuticals, Inc.	Celgene Corporation

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.