Phase II Randomized Study of SIR-Spheres, Yttrium Microspheres With Cetuximab Plus Irinotecan for Patients With Advanced Colorectal Cancer Metastases to the Liver
Yttrium microspheres are designed to treat cancer that has metastasized to the liver by
giving radiation directly to the tumor. SIR-spheres are designed to deliver radiation
directly to the tumor. This radiation kills the tumor cells.
Cetuximab is a drug that blocks epidermal growth factor receptor (EGFR). EGFR may be
involved in certain types of cancer, including non small-cell lung cancer (NSCLC). When
EGFR is stimulated, a series of chemical reactions start that result in a tumor being "told"
to grow. Cetuximab tries to stop these reactions by blocking EGFR. This may stop tumors
Irinotecan is designed to block cell growth by blocking an enzyme that repairs DNA, the
building blocks of cells.
If you agree to take part in this study, you will be randomly assigned (as in the toss of a
coin) to 1of 2 groups. Participants in one group will receive the SIR-spheres with
Cetuximab and Irinotecan therapy. Participants in the other group will just have the
Cetuximab and Irinotecan therapy without the SIR-spheres. There is an equal chance of
being assigned to either group.
If you are found to be eligible to take part in this study, you will have a blood vessel
study (given with x-ray dye) performed. This will help researchers look at the arteries
leading to your liver and the surrounding areas. You will receive Versed and Fentanyl,
sedative drugs to put you to sleep, intravenously (IV--through a needle in a vein) in your
arm. A catheter will be placed through your groin artery into the artery leading to your
liver. A catheter is a sterile flexible tube that will be placed into a large artery while
you are under local anesthesia and IV sedation. 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. X-ray dye will be injected through the catheter.
If randomly selected to receive the SIR-Spheres with Cetuximab and Irinotecan therapy, a
small amount of radioactive albumin injection (a part of a scan test used to measure the
supply of blood through the lungs) will be given to your liver. Images will then be taken
to learn if too much of this material (radioactive particles) shows up in your lungs and if
your liver anatomy is normal. If everything appears normal, the yttrium microspheres will be
given slowly through the catheter in 1 dose. If your liver anatomy is abnormal, the yttrium
microspheres will be given slowly through the catheter in 2 doses. After you are given the
yttrium microspheres, the catheter will be removed, and pressure will be applied to your
groin to stop any bleeding. You will then be monitored for 6 hours to check on your well
being. You will be given pain medication, if needed (the same sedative drugs used before).
You will be given standard doses of Zantac (ranitidine) to help to protect the stomach
during treatment. Chemotherapy with cetuximab and irinotecan will be given on an outpatient
basis. A catheter (PICC line, port-a-cath) may be inserted through a vein in your arm or
chest to ensure that the chemotherapy is given without interruption. Irinotecan will be
given by IV over 90 minutes, once every 3 weeks. Cetuximab will be given once a week. On
Day 1 of treatment, you will be given a test dose of cetuximab, to check for any allergic
reactions. After that, cetuximab will be given by IV over 2 hours. Before every dose of
cetuximab, you will be given a dose of diphenhydramine by IV, to keep from having any
allergic reactions. You will also receive medication to prevent nausea, vomiting, or an
You will have a single-photon emission computerized tomography (SPECT) scan within 1 week
after your treatment. A SPECT scan lets your doctor study the function of your internal
organs. You will have blood (about 2 tablespoons) drawn every week for the first 2 months
and then once a month on an outpatient basis. This is so researchers can check the function
of your kidneys and liver. You will also have a routine physical exam and a computerized
tomography (CT) scan performed once a month to check the growth of your tumor. Researchers
will check to see if your tumor is responding to the study treatment by looking at the
imaging on CT scans every 8 weeks.
You may be taken off this study if your disease gets worse, if you experience intolerable
side effects, or if there is not enough of the study drug supply to continue treating your
You will be followed-up by telephone for as long as you have cancer.
This is an investigational study. Yttrium microspheres are FDA approved for hepatic
arterial therapy and treatment of liver metastases. Sir-Sphere therapy has been approved
for treating colorectal cancer with liver metastases. The combination of cetuximab and
irinotecan is FDA approved for metastatic colorectal cancer. Up to 60 patients will take
part in this study. All will be enrolled at M. D. Anderson.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment
Progression Free Survival
Ravi Murthy, MD
UT MD Anderson Cancer Center
United States: Food and Drug Administration