Phase I/II Study of Celebrex and EPO906 in Patients With Metastatic Colorectal Cancer
This study is for people with advanced colorectal cancer. This study uses the drugs Celebrex and EPO906. EPO906 is an experimental drug that has not been approved by the FDA. EPO906 is a drug that has been shown in the laboratory to cause cancer cells to die and prevents them from growing and reproducing. Celebrex is a drug that is approved by the FDA for the treatment of arthritis and prevention of colon polyps. Colon polyps are small growths in the colon. If not surgically removed, some colon polyps can become cancerous. Some studies have shown that Celebrex may reduce the side effects of chemotherapy. Other studies have shown that it may increase the effectiveness of some chemotherapy. Celebrex is not approved by the FDA for reducing the side effects of chemotherapy or improving the effectiveness of chemotherapy. The combination of EPO906 and Celebrex in this study is experimental.
The main goal of this study is to see if adding the drug Celebrex to the drug EPO906 will decrease the amount of diarrhea seen in patients that receive EPO906.
The goal of the first phase of this study is to find the highest dose of EPO906 that can be given safely with Celebrex. The dose of Celebrex will remain the same for the whole study. Higher doses of EPO906 will be given to each group of patients. The increase of EPO906 will stop once more than one patient has serious side effects. The highest dose of EPO906 that can be given with Celebrex (without serious side effects) will be called the pilot dose.
The goal of the second phase of this study is to find out how tumors respond to these doses of the drugs. Another purpose of this study is to see how the body processes the EPO906 and Celebrex. This study will also look at the side effects of these drugs. In this study, we will measure how long subjects live, how often tumors shrink after receiving the study drugs, and how long it takes for tumors to increase in size after receiving the study drugs. This study will also measure the levels of genes, which are the cell's blueprint, in participant's tumors. Several genes can affect how people's bodies react to the cancer drugs. Genes will also be measured in participant's blood. We want to see if these predict response to the study drugs.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Celebrex and EPO906 in Patients With Metastatic Colorectal Cancer (CEPO906AUS10)|
- To determine the maximum tolerated dose (MTD) of Celebrex in combination with EPO906 in patients with metastatic colorectal cancer. [ Time Frame: One month ] [ Designated as safety issue: Yes ]
- Once MTD is established we propose to expand the dose level of the MTD to 62 new patients to evaluate whether the addition of Celebrex to EPO906 can reduce the incidence of grade 3-4 diarrhea to 6% or less. [ Time Frame: Until 30 days after patient receives last study drug ] [ Designated as safety issue: Yes ]
- To estimate the time to progression, survival and response rate in patients with metastatic colorectal cancer who failed 5-FU/LV, CPT-11 and/or oxaliplatin based hemotherapy and receive Celebrex in combination with EPO906. [ Time Frame: Until Patient goes off study ] [ Designated as safety issue: No ]
- To further assess toxicity of this regimen. [ Time Frame: 30 days after patient receives last dose ] [ Designated as safety issue: Yes ]
- To investigate whether the molecular biomarkers including protein expression changes from plasma, the expression levels of VEGF, E-cadherin, TP, COX-2, and β-tubulin in tumor tissue associated with clinical outcome for this regimen. [ Time Frame: Until Patient Death ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 2004|
|Estimated Study Completion Date:||January 2014|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Drug: EPO906, celecoxib
EPO906 IV, every three weeks, celecoxib by mouth twice a day every day
|United States, California|
|U.S.C./Norris Comprehensive Cancer Center|
|Los Angeles, California, United States, 90033|
|Principal Investigator:||Heinz-Josef Lenz, M.D.||U.S.C/Norris Cancer Center|