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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01189929




Registration number
NCT01189929
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 Gemcitabine and Demcizumab (OMP-21M18) With or Without Abraxane® as 1st-line Treatment in Subjects With Locally Advanced or Metastatic Pancreatic Cancer
Scientific title
A Phase 1b Study of Gemcitabine and Demcizumab (OMP-21M18) With or Without Abraxane® as 1st-line Treatment in Subjects With Locally Advanced or Metastatic Pancreatic Cancer
Secondary ID [1] 0 0
M18-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pancreatic Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Demcizumab
Treatment: Drugs - Abraxane®
Treatment: Drugs - Gemcitabine

Experimental: Gemcitabine and demcizumab With or Without Abraxane® - Gemcitabine and demcizumab With or Without Abraxane®


Treatment: Drugs: Demcizumab
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 you are enrolled in the study you will receive intravenous (in the vein) infusions of the demcizumab administered once every 2 weeks, and gemcitabine and Abraxane® administered weekly for 3 weeks, out of every 4 weeks. After 9 weeks, you will undergo assessments to determine the status of your disease. If there is no evidence of progression of your disease or if your tumor is smaller, you will continue to receive one additional infusion of demcizumab, and you will continue to receive infusions of gemcitabine and Abraxane® once weekly for 3 consecutive weeks out of every 4 weeks until it has been shown that your cancer has progressed. You will undergo assessments every 8 weeks thereafter to determine the status of your disease.

Treatment: Drugs: Abraxane®
Abraxane® which will be administered by IV infusion at a dose of 125 mg/m2 over 30 minutes once a week for 3 weeks in a row, followed by a week of rest.

Treatment: Drugs: Gemcitabine
Gemcitabine will be administered intravenously over 30 minutes initially at a dose of 1000 mg/m2 once a week for 3 weeks in a row, followed by a week of rest. If you develop side effects during this time period, your physician may decide to hold or reduce the dose of gemcitabine.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To determine the maximum tolerated dose of demcizumab (OMP-21M18) when combined with gemcitabine +/- Abraxane®
Timepoint [1] 0 0
Until disease progression
Secondary outcome [1] 0 0
To determine the safety of gemcitabine +/- Abraxane® plus demcizumab (OMP-21M18)
Timepoint [1] 0 0
Until disease progression
Secondary outcome [2] 0 0
To determine the rate of immunogenicity of gemcitabine +/- Abraxane® plus demcizumab (OMP-21M18)
Timepoint [2] 0 0
Until disease progression
Secondary outcome [3] 0 0
To determine the preliminary efficacy of gemcitabine +/- Abraxane® plus demcizumab (OMP-21M18)
Timepoint [3] 0 0
Until disease progression
Secondary outcome [4] 0 0
To determine population pharmacokinetics of demcizumab (OMP-21M18)
Timepoint [4] 0 0
Until disease progression
Secondary outcome [5] 0 0
To determine the exploratory biomarker changes of gemcitabine plus demcizumab (OMP-21M18)
Timepoint [5] 0 0
Until disease progression

Eligibility
Key inclusion criteria
Inclusion criteria

1. Subjects must have histologically or cytologically confirmed locally advanced or
metastatic pancreatic cancer. In addition, subjects must have a tumor that is at least
1 cm in a single dimension and is radiographically apparent on Computed Topography
(CT) or Magnetic Resonance Imaging (MRI). Prior chemotherapy or radiotherapy is not
allowed.

2. Age >21 years

3. Eastern Cooperative Oncology Group (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

- Creatinine <1.5 X institutional ULN OR

- 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 drug. 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 drug. 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 study drug, 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

11. Subjects with a blood pressure (BP) of >140/90 mmHg. Subjects taking antihypertensive
medications must be taking =2 medications to obtain this level of BP control.

12. Subjects with tumors that are currently involving the lumen of the gastrointestinal
tract

13. 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 of <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

14. Subjects with electrocardiogram (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
N/A
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
Single group
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
1/08/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2016
Sample size
Target
Accrual to date
Final
57
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [3] 0 0
The Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
Recruitment postcode(s) [3] 0 0
- Heidelberg
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Christchurch
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
experimental drug, demcizumab (OMP-21M18), when given in combination with gemcitabine with or
without (+/-) Abraxane®. Historically, single agent gemcitabine has been the standard
treatment for pancreatic cancer. However, recent data suggests that gemcitabine plus
Abraxane® may be superior to gemcitabine alone, thus this combination is emerging as the new
standard therapy for pancreatic cancer. However, Abraxane® has not been approved for the
treatment of pancreatic cancer at this time. Demcizumab is a humanized monoclonal antibody
and was developed to target cancer stem cells. This study is sponsored by OncoMed
Pharmaceuticals, which is referred to as OncoMed or the Sponsor in this consent form. The
study is designed to test the safety of demcizumab at different dose levels when given with
gemcitabine +/- Abraxane® and the effects, both good and bad, that it has on participants.
Demcizumab may block the growth of cancer stem cells, the remaining tumor cells, and it may
also prevent the growth of new blood vessels that tumors need to grow and spread. Although
demcizumab has been administered with gemcitabine to cancer patients, it has not been given
in combination with gemcitabine and Abraxane®; thus, it is not known if it will provide any
benefit to participants and may cause harmful side effects.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01189929
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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01189929