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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01189968




Registration number
NCT01189968
Ethics application status
Date submitted
25/08/2010
Date registered
27/08/2010
Date last updated
9/09/2020

Titles & IDs
Public title
A Study of Carboplatin and Pemetrexed Plus Demcizumab (OMP-21M18) in Subjects With Non-Squamous Non-Small Cell Lung Cancer
Scientific title
A Phase 1b Study of Carboplatin and Pemetrexed Plus Demcizumab (OMP-21M18) as 1st-line Treatment in Subjects With Non-Squamous Non-Small Cell Lung Cancer
Secondary ID [1] 0 0
M18-004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non Small Cell Lung Cancer 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 - Demcizumab

Experimental: Carboplatin and Pemetrexed plus demcizumab - Carboplatin and Pemetrexed plus demcizumab

Experimental: Pemetrexed plus demcizumab - Pemetrexed plus demcizumab


Treatment: Drugs: Demcizumab
The 6 subjects in the first cohort will receive demcizumab 5 mg/kg once every 3 weeks; the 6 subjects in the subsequent cohort will be treated with 10 mg/kg once every 3 weeks; and the 6 subjects in the final cohort will be treated with 15 mg/kg once every 3 weeks. A Data Safety Monitoring Board (DSMB) will review the data for the 6 subjects in each dose cohort after the last subject in that cohort has been on study for 56 days and then decide whether it is safe to escalate to the next highest dose cohort. Once the dose-escalation portion of the study has been completed, 14 additional subjects will be treated at the highest dose level that the DSMB deems as safe.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To the determine the maximum tolerated dose of demcizumab (OMP-21M18) plus carboplatin and pemetrexed
Timepoint [1] 0 0
When each patient in the dose cohort reaches Day 56
Secondary outcome [1] 0 0
To determine the safety of carboplatin and pemetrexed plus demcizumab (OMP-21M18)
Timepoint [1] 0 0
until treatment termination plus 30 days
Secondary outcome [2] 0 0
To determine the rates of immunogenicity of carboplatin and pemetrexed plus demcizumab (OMP-21M18)
Timepoint [2] 0 0
Up to 12 weeks post treatment termination
Secondary outcome [3] 0 0
To determine the preliminary efficacy of carboplatin and pemetrexed plus demcizumab (OMP-21M18)
Timepoint [3] 0 0
Until disease progression
Secondary outcome [4] 0 0
To determine population pharmacokinetics
Timepoint [4] 0 0
Day 21 and 63
Secondary outcome [5] 0 0
To determine the exploratory biomarker changes of carboplatin and pemetrexed plus demcizumab (OMP-21M18)
Timepoint [5] 0 0
Until Day 112

Eligibility
Key inclusion criteria
Inclusion criteria

1. Subjects must have histologically confirmed unresectable, locally advanced, recurrent, or metastatic non-squamous NSCLC. Subjects may not have received prior therapy for their unresectable, locally advanced, recurrent, or metastatic non-squamous NSCLC. Subjects may have received prior surgery, prior radiotherapy, and/or prior neoadjuvant or adjuvant chemotherapy (they must have discontinued prior neoadjuvant or adjuvant chemotherapy at least 12 weeks prior to study entry).
2. Age >21 years
3. ECOG performance status <2 (see Appendix B)
4. Life expectancy of more than 3 months
5. Subjects must have normal organ and marrow function as defined below:

* Leukocytes >3.5 x 109/L
* Absolute neutrophil count >1.25 x 109/L Hemoglobin >100 g/L
* Platelets >125 X 109/L
* Total bilirubin <2 X institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) <5 X institutional ULN
* Alkaline phosphatase <5 X institutional ULN
* International normalized ratio (INR) and activated partial thromboplastin time (aPTT) within institutional ULN
* Calculated creatinine clearance >60 mL/min using the Cockcroft and Gault formula as follows:

Creatinine clearance (mL/min) = (140 - age) x ideal body weight [kg] 0.814 x serum creatinine [µmol/L] For women multiply the value from the equation above by 0.85. Where age is in years, weight is in kg, and serum creatinine is in µmol/L.
6. Women of childbearing potential must have had a prior hysterectomy or have a negative serum pregnancy test and be using adequate contraception prior to study entry and must agree to use adequate contraception from study entry through at least 6 months after discontinuation of study drugs. Men must also agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and from study entry through at least 6 months after discontinuation of study drugs. Should a woman enrolled in the study or a female partner of a man enrolled in the study become pregnant or suspect she is pregnant while participating in this study or within 6 months after discontinuation of the study drugs, the Investigator should be informed immediately.
7. Ability to understand and the willingness to sign a written informed consent document
Minimum age
21 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

Subjects who meet any of the following criteria will not be eligible for participation in the study:

1. Subjects receiving any other investigational agents or anti-cancer therapy.
2. Subjects with brain metastases (subjects must have a CT scan or MRI of the head within 28 days prior to enrollment to rule out brain metastases), uncontrolled seizure disorder, or active neurologic disease
3. History of a significant allergic reaction attributed to humanized or human monoclonal antibody therapy
4. Significant intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
5. Pregnant women or nursing women
6. Subjects with known HIV infection
7. Known bleeding disorder or coagulopathy
8. Subjects receiving heparin, warfarin, or other similar anticoagulants. Note: Subjects may be receiving low-dose aspirin and/or non-steroidal anti-inflammatory agents.
9. Subjects with known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease
10. New York Heart Association Classification II, III, or IV (See Appendix D)
11. Subjects with a blood pressure of >140/90 mmHg. The BP should be taken using the method described in Section 9.3. Subjects taking antihypertensive medications must be taking = 2 medications to obtain this level of BP control.
12. Subjects with metastases that are currently involving the lumen of the gastrointestinal tract
13. Subjects with squamous cell carcinoma of the lung
14. Subjects with recent (within the last 8 weeks) hemoptysis >2.5 mL and subjects with serious bleeding from another site within this timeframe
15. Subjects with current evidence of cardiac ischemia or heart failure within the last 6 months, subjects who are receiving any medications for cardiac ischemia, subjects with a B-type natriuretic peptide (BNP) value of >100 pg/mL, subjects with a LVEF <50%, subjects with pulmonary hypertension defined as a peak tricuspid velocity >3.4 m/s on doppler echocardiogram or subjects that have received a total cumulative dose of =400 mg/m2 doxorubicin.
16. Subjects with ECG evidence of ischemia or = Grade 2 ventricular arrhythmia, subjects who have a history of acute myocardial infarction within 6 months, or subjects with unstable angina.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
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
1/09/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2016
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Brisbane & Women's Hospital - Herston
Recruitment hospital [2] 0 0
Ashford Cancer Centre Research - Kurralta Park
Recruitment hospital [3] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [4] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Hamilton
Country [3] 0 0
Spain
State/province [3] 0 0
Madrid

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
Novotech (Australia) Pty Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to test the safety and determine the optimal dose of a new drug, demcizumab (OMP-21M18), when given in combination with carboplatin and pemetrexed, a standard drug treatment regimen for non-squamous non-small cell lung cancer (NSCLC). Participants must not have received prior chemotherapy for their NSCLC. Demcizumab is a humanized monoclonal antibody (a protein made in the laboratory) developed to target cancer stem cells. The way the body handles demcizumab will also be investigated.

Up to 50 subjects will be enrolled at up to 8 centers in Australia, New Zealand, and Spain. Up to 28 days (4 weeks) prior to treatment you will undergo testing to determine your eligibility to take part in this study, and then if enrolled in the study you will receive intravenous (in the vein) infusions of the demcizumab, carboplatin, and pemetrexed administered on the same day, every 21 days for 4 cycles, or until it has been shown that your cancer has progressed. 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. You will undergo assessments every 8 weeks to determine the status of your disease.
Trial website
https://clinicaltrials.gov/study/NCT01189968
Trial related presentations / publications
McKeage MJ, Kotasek D, Markman B, Hidalgo M, Millward MJ, Jameson MB, Harris DL, Stagg RJ, Kapoun AM, Xu L, Hughes BGM. Phase IB Trial of the Anti-Cancer Stem Cell DLL4-Binding Agent Demcizumab with Pemetrexed and Carboplatin as First-Line Treatment of Metastatic Non-Squamous NSCLC. Target Oncol. 2018 Feb;13(1):89-98. doi: 10.1007/s11523-017-0543-0.
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01189968