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
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
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
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
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
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
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
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
Apostolia M. Tsimberidou, MD, PhD
M.D. Anderson Cancer Center
United States: Institutional Review Board
|U.T.M.D. Anderson Cancer Center||Houston, Texas 77030|