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A Phase 1b Study of FOLFIRI Plus OMP-21M18 as 1st or 2nd-line Treatment in Subjects With Metastatic Colorectal Cancer

Phase 1
21 Years
Open (Enrolling)
Colorectal Cancer

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Trial Information

A Phase 1b Study of FOLFIRI Plus OMP-21M18 as 1st or 2nd-line Treatment in Subjects With Metastatic Colorectal Cancer

Current cancer therapies often produce an initial reduction in tumour size but may not have
longterm benefits. One possible explanation for this is the presence cancer cells known as a
cancer stem cells. Cancer stem cells represent a small part of the tumour but are believed
to be responsible for much of the growth and spread of the cancer. They may also be more
resistant to traditional types of therapy, such as chemotherapy and radiation therapy.

The purpose of this study is to test the safety and determine the optimal dose of a new
experimental drug, OMP-21M18, when given in combination with FOLFIRI, a chemotherapy regimen
consisting of the following three medications: folinic acid (leucovorin), 5fluorouracil and
irinotecan. The administration of these three medications is a standard treatment for
advanced colorectal cancer. OMP-21M18 is a humanized monoclonal antibody (a protein made in
the laboratory) developed to target cancer stem cells. The way the body handles OMP21M18
will also be investigated.

Up to 32 participants, 21 years or older, will be enrolled at up to 6 centres in Australia
and New Zealand. Following informed consent and screening, FOLFIRI will be administered once
every 14 days (or until toxicity necessitates reducing or delaying a dose). OMP-21M18 will
be administered by intravenous (IV) infusion once every 14 days on the same day as FOLFIRI.
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.

Participants will be assessed for disease status every 8 weeks and for safety at every visit
and for 30 days after the end of study drug treatment. Safety will be assessed by adverse
event monitoring, physical examination, vital signs, blood tests, cardiac monitoring, and
participant interview. Response rates, duration of response, time to progression, and
survival will be evaluated requiring CT or MRI scans and CEA (tumour marker) levels at
baseline and then every 8 weeks. The development of antibodies to treatment will be assessed
throughout the study and up to 12 weeks after the end of study drug treatment. During the
study blood samples will be taken to assess whether OMP21M18 is producing desired changes to
the genes and proteins related to the cancer (biomarkers). The study includes an optional
part which will investigate how variations in people's genetic makeup affect their response
to medications. This involves the collection of one blood sample just before participants
receive their first dose of study treatment. DNA will be extracted from the blood sample for

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

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

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

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

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

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

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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To the determine the maximum tolerated dose of OMP-21M18 plus FOLFIRI

Outcome Time Frame:

Will be done after each patient in dose cohort reaches Day 56

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

September 2010

Completion Date:

May 2013

Related Keywords:

  • Colorectal Cancer
  • Phase 1
  • dose escalation
  • histologically
  • confirmed
  • malignancy
  • metastatic
  • Colorectal Neoplasms