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Phase II Randomized Study of SIR-Spheres, Yttrium Microspheres With Cetuximab Plus Irinotecan for Patients With Advanced Colorectal Cancer Metastases to the Liver

Phase 2
18 Years
Not Enrolling
Colon Cancer, Colorectal Cancer

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Trial Information

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
from growing.

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
allergic reaction.

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.

Inclusion Criteria:

1. Patients must have histologically or cytologically confirmed adenocarcinoma of the
colon or rectum. Histology from the hepatic metastasis is not mandatory if the
morphological appearances on cross sectional imaging and tumor markers (CEA) are
indicative of a colorectal primary.

2. Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in two dimensions (longest diameter to be recorded) as greater
than or equal to 20 mm with conventional techniques or as greater than or equal to 10
mm with spiral CT scan.

3. Patients must have radiological evidence of disease progression of disease within 6
months of their most recent dose of chemotherapeutic regimens .

4. Age greater than or equal to 18 years.

5. ECOG performance status less than or equal to 2.

6. Patients must have normal organ and marrow function as defined below within 30 days
of receiving the investigational agent: - leukocytes greater than or equal to
3,000/mL - absolute neutrophil count greater than or equal to 1,500/mL - platelets
greater than or equal to 100,000/mL - total bilirubin less than or equal to 1.5 times
upper limits of normal institutional limits - AST(SGOT) less than or equal to 3 X ULN
and ALT(SGPT) less than or equal to 3 X ULN - Creatinine less than or equal to 1.5
times upper limits of normal institutional limits

7. Patients with a prior history of non-colorectal cancer who have no active disease may
be eligible if they are disease free for greater than or equal to 12 months prior to

8. The effects of SIR-Spheres, irinotecan or cetuximab on the developing human fetus at
the recommended therapeutic dose are unknown. For this reason and because radiation
as well as other therapeutic agents used in this trial are known to be teratogenic,
women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation. Should a woman become pregnant or suspect
she is pregnant while in this study, she should inform her treating physician

9. Ability to understand and the willingness to sign a written informed consent

10. Patients without evidence of local disease recurrence from colorectal cancer are

11. Patients with extrahepatic disease confined to the lung is permitted if < 4 lesions
are depicted on CTand all are < 3 cm in size

12. Patients with brain mets are eligible for this trial if those patients who have had
the area surgically resected or irradiated and have no evidence of active disease as
demonstrated by MRI of the brain. Patients must have no evidence of residual
neurological dysfunction as per baseline neurological exam. Patients with untreated
brain metastases will be considered ineligible.

Exclusion Criteria:

1. Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or
mitomycin C) prior to entering the study or those who have not recovered from adverse
events due to agents administered more than 4 weeks earlier will be excluded.
Patients who have had hepatic external beam radiotherapy will be excluded.

2. Patients may not be receiving any other investigational agents.

3. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to SIR-Spheres, irinotecan or cetuximab or other agents used in the

4. Evidence of ascites, biopsy proven cirrhosis or portal hypertension suggested by the
presence of characteristic imaging features on cross sectional imaging or esophageal
varicosities demonstrated on endoscopy or barium swallow. A diagnostic study to rule
out the presence of portal hypertension will not be required unless the findings on
cross sectional imaging are suggestive but not confirmatory.

5. Hepatic arterial anatomy that would prevent catheterization and the administration of
SIR-Spheres into the liver.

6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection requiring hospital admission or antibiotics,symptomatic congestive heart
failure (class III and IV), unstable angina pectoris, cardiac arrhythmia, or
psychiatric illness/social situations would exclude patients from this study.

7. Contraindications to angiography and selective visceral catheterization: History of
severe allergy or intolerance to any contrast media, or atropine. Bleeding diathesis,
not correctable by usual forms of therapy that would include medical coagulopathy but
not limited to the administration of blood products.

8. Utilization of capecitabine for the 6 weeks preceding SIR-Sphere therapy and
indefinitely following SIR-Sphere therapy as per manufacturer's recommendations due
to the increased risk of radiation hepatitis.

9. Patients exhibiting the mutant variety for kras will be excluded for participation in
the study.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Outcome Measure:

Progression Free Survival

Outcome Time Frame:

4 Months

Safety Issue:


Principal Investigator

Ravi Murthy, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

October 2009

Completion Date:

January 2012

Related Keywords:

  • Colon Cancer
  • Colorectal Cancer
  • Colon
  • Liver
  • Colorectal cancer
  • Colorectal cancer metastases to the liver
  • Metastases to the liver
  • Colorectal cancer mets to liver
  • Colon cancer metastasized to liver
  • Yttrium microspheres
  • SIR-Spheres
  • Yttrium-90
  • Cetuximab
  • C225
  • Erbitux
  • IMC-C225
  • Irinotecan
  • CPT-11
  • Liver directed therapy
  • Colonic Neoplasms
  • Colorectal Neoplasms