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Phase I Trial of Cetuximab and Erlotinib (EGFR Inhibitors) and SIR-Spheres (Yttrium Microspheres) in Patients With Advanced Malignancies and Liver Metastases

Phase 1
18 Years
Not Enrolling
Advanced Cancers

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Trial Information

Phase I Trial of Cetuximab and Erlotinib (EGFR Inhibitors) and SIR-Spheres (Yttrium Microspheres) in Patients With Advanced Malignancies and Liver Metastases

Study Groups:

If you are found to be eligible to take part in this study, your doctor will decide which
group you will be in based on your medical history.

- Group 1 will receive SIR-Spheres with yttrium-90 attached and cetuximab.

- Group 2 will receive SIR-Spheres with yttrium-90 attached, cetuximab, and erlotinib.

Once it is decided which combination you will receive, you will be assigned to a dose level
of cetuximab based on when you join the study. Up to 3 dose levels of cetuximab will be
tested. Three (3) to 6 participants will be enrolled at each dose level. The first group
of participants will receive the lowest dose level. Each new group will receive a higher
dose than the group before it, if no intolerable side effects were seen. This will continue
until the highest tolerable doses of the combinations are found.

All study participants will receive a dose level of the SIR-Spheres with yttrium-90 attached
based on the results of the "break-through" scan (described below).

If you are assigned to Group 2, you will also receive erlotinib. If you are tolerating
erlotinib well after 1 cycle, you may begin receiving a higher dose of erlotinib in Cycle 3
and beyond.

Break-through Scan:

You will have a "break-through" scan within 29 days before receiving the SIR-Spheres with
yttrium-90 microspheres. This scan will measure the supply of blood in your lungs and will
also be used to check your liver. For this test, a small amount of radioactive material will
be injected into your liver and images will be taken to see how the material moves through
your lungs and liver. The radioactive material will be given through a catheter in a vein in
your groin. A catheter is a sterile, flexible tube that will be placed through your groin
artery into the artery leading to your liver while you are under local anesthesia. Your
doctor will explain this procedure to you in more detail.

The results of this test will be used to determine if you will receive a full or partial
dose of SIR-Spheres with yttrium-90 microspheres.

Radiation and Study Drug Administration:

Each study cycle is 28 days.

You will receive the SIR-Spheres with yttrium-90 microspheres on Day 1 of Cycle 1 only.
Before you receive the SIR-Spheres with Yttrium-90 microspheres, you will receive sedative
drugs by vein to put you to sleep. SIR-Spheres with yttrium-90 microspheres will then be
given to you through a catheter in a vein in your groin.

After you are given the yttrium-90 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 for any side effects. If needed, you will be given pain medication after the
infusion. Your study doctor will decide which pain medications to give you.

Cetuximab will be given by vein 1 time each week during Weeks 2-4 of Cycle 1, and then 1
time every week for Cycles 2 and beyond. The first time you receive cetuximab, it will be
given over 2 hours. Every time you receive cetuximab after that, it will be given over 1

If you are assigned to receive erlotinib, you will take it by mouth 1 time each day starting
on Day 1 of Cycle 2. You should take it at the same time each day . You should take it on
an empty stomach either 1 hour before or 2 hours after eating. The study staff will give you
more instructions for taking erlotinib.

Study Visits:

On Day 1 of Cycle 1:

- Before you receive the SIR-Spheres with yttrium-90 microspheres, your blood vessels
will be checked. For this test, you will receive an x-ray dye through the catheter that
will help the study staff look at the arteries leading to your liver and surrounding

- You will have a physical exam and your medical history will be recorded.

- Blood (about 2 teaspoons) will be drawn for routine tests.

During Weeks 2 and 4 of Cycle 1:

- You will have a physical exam and your medical history will be recorded.

- Blood (about 2 teaspoons) will be drawn for routine tests.

Every 8 weeks, you will have an x-ray, CT scan, MRI scan, and/or PET/CT scan to check the
status of the disease.

About every 4 weeks starting at the beginning of Cycle 2:

- You will have a physical exam and your medical history will be recorded

- Blood (about 2 teaspoons) will be drawn for routine tests. This routine blood draw will
include a pregnancy test if you are able to become pregnant.

Length of Study:

You receive the study drugs for as long as you are benefitting. You will no longer be able
to take the study drug if the disease gets worse, if intolerable side effects occur, or if
you are unable to follow study directions.

This is an investigational study. SIR-Spheres are FDA-approved and commercially available
to treat metastatic colorectal cancer that has spread to the liver. Yttrium-90 microspheres
are FDA-approved for hepatic arterial therapy and the treatment of liver metastases.
Cetuximab is FDA-approved and commercially available to treat head and neck and colorectal
cancer. Erlotinib is FDA-approved and commercially available to treat non-small cell lung
cancer (NSCLC) and pancreatic cancer. The use of this combination to treat advanced cancer
is investigational.

Up to 136 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Patients with advanced or metastatic cancer in the liver, with measureable or
evaluable disease, that is refractory to standard therapy, relapsed after standard
therapy, or who have no standard therapy available that improves survival by at least
three months

2. Patients must be >/= 3 weeks beyond treatment with a cytotoxic chemotherapy regimen,
or therapeutic radiation, or major surgery. Patients may have received palliative
localized radiation immediately before or during treatment providing radiation is not
delivered to the only site of disease being treated under this protocol

3. ECOG performance status
4. Patients must have organ and marrow function defined as: • Absolute neutrophil count
>/= 500/mL; • Platelets >/=50,000/mL; creatinine 2.0; ALT(SGPT)
5. Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence).

6. Patients must be able to understand and be willing to sign a written informed consent

Exclusion Criteria:

1. Pregnant or lactating women.

2. Patients who have had hepatic external beam radiotherapy.

3. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to SIR-Spheres, cetuximab, or erlotinib.

4. Patients with colorectal cancer with known kRAS mutation

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

6. Greater than 20% arterio-venous shunting of SIR-Spheres to the lungs estimated from a
Technetium-99m-macro-aggregated albumin (99mTc-MAA) nuclear medicine break-through

7. Contraindication to angiography and selective visceral catheterization: History of
severe allergy or intolerance to any contract 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-Spheres therapy and
indefinitely following SIR-Spheres therapy as per manufacturer's recommendations due
to the increased risk of radiation hepatitis.

9. 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD)

Outcome Description:

Maximum tolerated dose (MTD) is defined as the highest dose studied in which the incidence of dose limiting toxicities (DLT) was less than 33% of treated population.

Outcome Time Frame:

8 weeks

Safety Issue:


Principal Investigator

Aung Naing, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

December 2012

Completion Date:

Related Keywords:

  • Advanced Cancers
  • Advanced Cancers
  • Advanced Malignancies
  • Liver Metastases
  • SIR-Spheres
  • Selective internal radiation
  • Yttrium-90
  • Cetuximab
  • C225
  • Erbitux
  • Erlotinib
  • Erlotinib Hydrochloride
  • Tarceva
  • OSI-774
  • Neoplasms