Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, Leucovorin, and Avastin
- To determine the toxicity and tolerability of intra-arterial hepatic oxaliplatin every three weeks administered in combination with systemic intravenous Fluorouracil, Leucovorin and bevacizumab to patients with advanced solid tumors metastatic to the liver.
- To document in a descriptive fashion the antitumor efficacy of this combination regimen.
- To evaluate the feasibility and accuracy of an alternate radiographic assessment tool and compare with available tumor markers and RECIST guidelines.
- To estimate in a descriptive fashion the development of extrahepatic tumor recurrences.
Advanced Solid Tumors
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Hepatic Arterial Infusion of Oxaliplatin in Combination With Systemic Fluorouracil, Leucovorin and Avastin for Patients With Advanced Solid Tumors Metastatic to the Liver|
- To study the highest tolerable dose of oxaliplatin used in combination with 5-fluorouracil, leucovorin, and Avastin® (bevacizumab) for patients with advanced cancer that has spread to the liver. [ Time Frame: 5 Years ] [ Designated as safety issue: Yes ]
|Study Start Date:||June 2006|
|Study Completion Date:||January 2010|
|Primary Completion Date:||January 2010 (Final data collection date for primary outcome measure)|
|Experimental: Oxaliplatin + Fluorouracil + Leucovorin + Avastin||
300 mg/m^2 IV over 10 Minutes, then 600 mg/m^2 IV over 22 Hours repeated every 3 weeks (1 Cycle).
Other Names:Drug: Avastin
10 mg/m^2 IV Over 90 Minutes repeated every 3 weeks (1 Cycle).
Other Name: BevacizumabDrug: Leucovorin
200 mg/m^2 IV Over 2 Hours repeated every 3 weeks (1 Cycle).Drug: Oxaliplatin
60 mg/m^2 IV Over 2 Hours repeated every 3 weeks (1 Cycle).
Hide Detailed Description
Oxaliplatin is designed to interfere with the growth of cancer cells (which slows their growth and spreading), eventually destroying them.
5-fluorouracil is designed to interfere with the growth of cells that reproduce rapidly.
Leucovorin is designed to strengthen the effect of 5-fluorouracil by reducing tumor cell resistance to the 5-fluorouracil.
Bevacizumab is designed to interfere with blood flow to your tumors, which may cause tumors to be "starved" of the oxygen and nutrients they need to grow.
Before you can start on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. You will have your complete medical history recorded and a physical exam, including measurement of your vital signs (blood pressure, temperature, breathing rate, and heart rate). You will have a neurological evaluation (a test to evaluate your strength and nerve functioning). You will have blood drawn (about 1 teaspoon or less) and urine collected for routine tests. Women who are able to have children must have a negative urine pregnancy test.
If you are found to be eligible to take part in this study, you will be hospitalized to receive the study drug combination. On the day of your admission to the hospital, you will have a catheter in your hepatic artery placed in your right groin. After your catheter has been placed, you will receive the study drugs. The catheter will be placed and removed during each cycle. A catheter is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your physician will explain this procedure to you in more detail, and you will be required to sign a separate consent form for this procedure.
You must lay in bed for the entire time that the catheter is in place. In some cases, the catheter will be removed immediately after your chemotherapy is complete. In some cases, the catheter may remain in overnight. Therefore, you must remain in bed until the catheter is removed.
During each cycle (on Days 1 and 2), you will receive 5-fluorouracil by vein continuously over 24 hours, leucovorin by vein over 1 hour, oxaliplatin by your hepatic artery over 2 hours, and bevacizumab by vein (only on Day 1) over about 1 1/2 hours. This study drug combination will be repeated about every 3 weeks, which is considered 1 cycle (about every 21 days).
To learn the highest tolerable dose of oxaliplatin when given in combination with the other study drugs, there will be a dose escalation process that will go as follows. The dose of oxaliplatin that you receive will depend on when you are enrolled in this study. The dose of the other 3 study drugs that you receive will be the same for each participant on this study. At first, 6 participants will be enrolled at the first dose level of oxaliplatin. If their disease does not get worse and no intolerable side effects occur, there will be another 6 patients enrolled at the next higher dose level. This dose escalation process will continue in this way until 8 dose levels have been reached without intolerable side effects occurring.
You will have blood drawn (about 2 teaspoons each) for blood counts and liver function tests before each dose of the study drug combination. This is so your doctor can check the safety of the drug combination. You will also have blood drawn (about 2 teaspoons each) before each cycle. The doctor will evaluate your disease and health before you receive the study drugs. Your tumors will be evaluated by the imaging scans (such as computed tomography [CT] and magnetic resonance imaging [MRI]) needed for your type of cancer. Imaging scans will be performed every 2 cycles.
You may continue to receive the study drug combination indefinitely as mentioned above unless your disease gets worse or you experience any intolerable side effects. If your disease gets worse or you experience any intolerable side effects, you will be removed from this study.
If your participation ends for any reason on this study (such as those mentioned above), you will have imaging scans (CT and MRI) to see if your tumors are growing or shrinking. You will have blood drawn (about 3 teaspoons) for routine tests. These end-of-study tests can be performed at your regular doctor's office, and the results will be sent to the study's research staff.
This is an investigational study. Oxaliplatin is authorized by the FDA for systemic use only. (Systemic therapies affect the body as a whole.) Giving oxaliplatin directly into the liver is investigational. 5-fluorouracil, leucovorin, and bevacizumab are FDA-approved for treatment of colorectal cancer. The use of these drugs in combination is authorized by the FDA for use in research only. Bevacizumab is not FDA-approved for all cancer types included in this study. Up to 163 patients will take part in this study. All patients will be enrolled at M. D. Anderson.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00507585
|United States, Texas|
|U.T.M.D. Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Apostolia M. Tsimberidou, MD, PhD||M.D. Anderson Cancer Center|