The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02259582




Registration number
NCT02259582
Ethics application status
Date submitted
17/09/2014
Date registered
8/10/2014
Date last updated
20/08/2018

Titles & IDs
Public 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
Scientific 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
Secondary ID [1] 0 0
M18-007
Universal Trial Number (UTN)
Trial acronym
DENALI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Nonsquamous Nonsmall Cell Neoplasm of Lung 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pemetrexed
Treatment: Drugs - Carboplatin
Treatment: Drugs - demcizumab

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

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

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


Treatment: Drugs: Pemetrexed


Treatment: Drugs: Carboplatin


Treatment: Drugs: demcizumab


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
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.

Eligibility
Key inclusion criteria
Main

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
Minimum age
21 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
The Kinghorn Cancer Centre - Darlinghurst
Recruitment hospital [3] 0 0
North Coast Cancer Institute Port Macquarie Base Hospital - Port Macquarie
Recruitment hospital [4] 0 0
Royall Brisbane & Women's Hospital - Herston
Recruitment hospital [5] 0 0
Icon Cancer Foundation - Milton
Recruitment hospital [6] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment hospital [7] 0 0
Monash Health, Monash Cancer Centre-Moorabbin - Bentleigh East
Recruitment hospital [8] 0 0
St. John of God Subiaco Hospital - Subiaco
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [4] 0 0
4029 - Herston
Recruitment postcode(s) [5] 0 0
4064 - Milton
Recruitment postcode(s) [6] 0 0
5011 - Woodville South
Recruitment postcode(s) [7] 0 0
3165 - Bentleigh East
Recruitment postcode(s) [8] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
Belgium
State/province [12] 0 0
Antwerpen
Country [13] 0 0
Belgium
State/province [13] 0 0
Charleroi
Country [14] 0 0
Belgium
State/province [14] 0 0
La Louviere
Country [15] 0 0
Belgium
State/province [15] 0 0
Liege
Country [16] 0 0
Italy
State/province [16] 0 0
Lombardia
Country [17] 0 0
Italy
State/province [17] 0 0
Piemonte
Country [18] 0 0
Italy
State/province [18] 0 0
Pordenone
Country [19] 0 0
Italy
State/province [19] 0 0
Toscana
Country [20] 0 0
Spain
State/province [20] 0 0
Barcelona
Country [21] 0 0
Spain
State/province [21] 0 0
Madrid
Country [22] 0 0
Spain
State/province [22] 0 0
Avila
Country [23] 0 0
Spain
State/province [23] 0 0
Sevilla

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
OncoMed Pharmaceuticals, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Celgene Corporation
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/show/NCT02259582
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications