ZD6474, Cetuximab, and Irinotecan in Patients With Metastatic Colorectal Cancer
This research study will test the safety of the investigational drug, ZD6474, in combination with 2 other drugs that are standard in the treatment of colon and rectal cancer (cetuximab and irinotecan). ZD6474 blocks the action of two substances in the body: vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR). VEGFR stimulates the formation of new blood vessels. When cancer cells produce VEGFR, new blood vessels are made that provide blood to the cancer cells. The blood carries nutrients and oxygen, allowing the cancer cells to live and grow. EGFR controls how quickly cells grow and multiply. Both of these substances are found on normal cells, but they are found in much higher levels on cancer cells.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of ZD6474, Cetuximab, and Irinotecan in Patients With Metastatic Colorectal Cancer|
- To determine the tolerability and maximum tolerated dose of combining ZD6474, cetuximab and irinotecan in patients with metastatic colorectal cancer refractory to prior cytotoxic chemotherapy. [ Time Frame: Years ] [ Designated as safety issue: Yes ]
- Determine response rate, progression-free survival and overall survival of adding ZD6474 to cetuximab and irinotecan in this patient population. [ Time Frame: Years ] [ Designated as safety issue: No ]
|Study Start Date:||February 2007|
|Study Completion Date:||August 2012|
|Primary Completion Date:||February 2012 (Final data collection date for primary outcome measure)|
- The main purpose is to find the highest dose of ZD6474 that is safe to give in combination with cetuximab and irinotecan. We will also be collecting information on how the body responds to the study drugs and what effects, good or bad, it has on treatment of colon and rectal cancer.
- Initially we plan to add ZD6474 to cetuximab alone. Small groups of participants will be enrolled in steps. The first group will be given a certain dose of ZD6474 and cetuximab. If the participants have few or manageable side effects, the next small group of people will receive a higher dose of ZD6474. This increase will continue until the study doctors find the highest dose that can be given.
- Once we determine the highest dose of ZD6474 with cetuximab, we will add irinotecan at increasing doses to determine the safety of all three drugs combined. The participant will know whether they are receiving the two or three drug combination.
- In order to confirm the safety of combining these drugs and to understand more how they work and interact with each other, some participants on this study will take just the ZD6474 for 2 weeks prior to starting the cetuximab and/or irinotecan.
- Each cycle of treatment is 8 weeks long. All participants will start taking ZD6474 orally, on day one and continue taking it at home thereafter. Cetuximab and irinotecan are given intravenously. Cetuximab is given once a week. Irinotecan will be given to participants that enter the trial once the safe dose of ZD6474 and cetuximab is determined. Irinotecan is given on Day 15 of cycle one, then every other week.
- Participants will be asked to visit the clinic every week for the first three weeks they are on the study. After the first three weeks, they will be required to visit with the doctor every other week. These visits will include physical exams, routine blood tests, scans, and other tests or procedures to monitor health.
- In addition to routine blood tests, blood tests for research will be done on the last 10 subjects on the trial. Test results from this sample will be used to evaluate the participants condition.
- In order to be treated on this study, a tumor tissue specimen must ba available for research testing. The specimen will be taken from a biopsy that was done before the participant enrolled on the study.
- Participants can continue on the study drug as long as they tolerate the drug and the cancer does not grow.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00436072
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02215|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||Jeffrey Meyerhardt, MD||Dana-Farber Cancer Institute|