A Study of FOLFIRI Plus OMP-21M18 as 1st or 2nd-line Treatment in Subjects With Metastatic Colorectal Cancer
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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1b Study of FOLFIRI Plus OMP-21M18 as 1st or 2nd-line Treatment in Subjects With Metastatic Colorectal Cancer|
- To the determine the maximum tolerated dose of OMP-21M18 plus FOLFIRI [ Time Frame: Will be done after each patient in dose cohort reaches Day 56 ] [ Designated as safety issue: Yes ]
- To determine the safety of FOLFIRI plus OMP-21M18 at two dose levels [ Time Frame: Until disease progression plus 30 days after ] [ Designated as safety issue: Yes ]
- To determine the rates of immunogenicity of FOLFIRI plus OMP-21M18 [ Time Frame: Up until 12 weeks after patient has Disease Progression ] [ Designated as safety issue: No ]
- To determine population pharmacokinetics [ Time Frame: Until Disease Progression ] [ Designated as safety issue: No ]
- To determine the exploratory biomarker changes of FOLFIRI plus OMP 21M18 [ Time Frame: Until Disease Progression ] [ Designated as safety issue: No ]
- To determine the preliminary efficacy of FOLFIRI plus OMP-21M18 [ Time Frame: Until Disease Progression ] [ Designated as safety issue: No ]
|Study Start Date:||September 2010|
|Study Completion Date:||February 2011|
|Primary Completion Date:||February 2011 (Final data collection date for primary outcome measure)|
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 testing.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01189942
|Australia, New South Wales|
|Sydney Cancer Centre|
|Camperdown, New South Wales, Australia, 2050|
|Royal Brisbane & Women's Hospital|
|Herston, Queensland, Australia, 4029|
|Australia, South Australia|
|Ashford Cancer Centre Research|
|Kurralta Park, South Australia, Australia, 5037|
|Australia, Western Australia|
|Sir Charles Gairdner Hospital|
|Nedlands, Western Australia, Australia, 6009|
|Hamilton, New Zealand, 3240|