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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/NCT01189942




Registration number
NCT01189942
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 FOLFIRI Plus OMP-21M18 as 1st or 2nd-line Treatment in Subjects With Metastatic Colorectal Cancer
Scientific title
A Phase 1b Study of FOLFIRI Plus OMP-21M18 as 1st or 2nd-line Treatment in Subjects With Metastatic Colorectal Cancer
Secondary ID [1] 0 0
M18-003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - OMP-21M18

Treatment: Drugs: OMP-21M18
The first 6 participants will receive OMP21M18 2.5 mg/kg once every other week, the next 6 participants will receive 5 mg/kg once every other week, and the final 6 participants will receive 10 mg/kg once every other week. A Data Safety Monitoring Board (DSMB) will review the data for the 6 participants in each dose level after the last participant in that group has been treated for 56 days and decide whether it is safe to move up to the next highest dose level. After confirming the optimum dose, 14 additional participants will be treated at the highest dose level that the DSMB considers 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 OMP-21M18 plus FOLFIRI
Timepoint [1] 0 0
Will be done after each patient in dose cohort reaches Day 56
Secondary outcome [1] 0 0
To determine the safety of FOLFIRI plus OMP-21M18 at two dose levels
Timepoint [1] 0 0
Until disease progression plus 30 days after
Secondary outcome [2] 0 0
To determine the rates of immunogenicity of FOLFIRI plus OMP-21M18
Timepoint [2] 0 0
Up until 12 weeks after patient has Disease Progression
Secondary outcome [3] 0 0
To determine population pharmacokinetics
Timepoint [3] 0 0
Until Disease Progression
Secondary outcome [4] 0 0
To determine the exploratory biomarker changes of FOLFIRI plus OMP 21M18
Timepoint [4] 0 0
Until Disease Progression
Secondary outcome [5] 0 0
To determine the preliminary efficacy of FOLFIRI plus OMP-21M18
Timepoint [5] 0 0
Until Disease Progression

Eligibility
Key inclusion criteria
Inclusion criteria

1. Subjects must have histologically confirmed metastatic colorectal cancer. Subjects may
not have received more than 1 prior chemotherapy regimen for their metastatic disease
and may not have received irinotecan for treatment of their metastatic disease.

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

- 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 (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 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 >200 pg/mL, subjects with a LVEF < 45%, or
subjects that have received a total cumulative dose of =400 mg/m2 doxorubicin.

14. 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
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
1/09/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2011
Sample size
Target
Accrual to date
Final
18
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA
Recruitment hospital [1] 0 0
Sydney Cancer Centre - Camperdown
Recruitment hospital [2] 0 0
Royal Brisbane & Women's Hospital - Herston
Recruitment hospital [3] 0 0
Ashford Cancer Centre Research - Kurralta Park
Recruitment hospital [4] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Hamilton

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,
OMP-21M18, when given in combination with FOLFIRI, a standard drug treatment for advanced
colorectal cancer. Participants must not have had more than one chemotherapy regimen for
their metastatic disease. OMP-21M18 is a humanized monoclonal antibody (a protein made in the
laboratory) developed to target cancer stem cells. The way the body handles OMP-21M18 will
also be investigated.

Up to 32 participants, 21 years or older, at up to 6 centres in Australia and New Zealand,
will receive intravenous infusions of OMP-21M18 followed by FOLFIRI every two weeks, until
disease progression or limited by drug toxicity. After 8 weeks, participants will undergo
assessments to determine their disease status. If there is no evidence of disease progression
participants will continue to receive infusions of OMP-21M18 and FOLFIRI every second week,
until disease progression.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01189942
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/NCT01189942