Trial Information

Erlotinib Prevention of Oral Cancer (EPOC)

Erlotinib hydrochloride is designed to block the activity of an enzyme found on the surface
of many tumor cells that may control tumor growth and survival. This may keep tumors from
growing.

Before you can start treatment on this study, you will have what are called "screening
tests." These tests will help the doctor decide if you are eligible to take part in the
study. Your complete medical history will be recorded, including your smoking and alcohol
usage. You will have a physical exam performed, including measurement of vital signs (blood
pressure, heart rate, temperature, and breathing rate). A performance status evaluation (a
test looking at the ability to perform everyday activities) will be done. You will have a
careful examination of the inside of your mouth.

The first part of screening involves testing some of your tumor tissue. This can be done
with tissue samples that were already removed within the last 12 months for your original
diagnosis. However, if there is not enough of the existing tissue sample or your doctor
decides that you will need another biopsy for screening, you will have a biopsy taken (a
small piece of tissue about the size of a small seed) from the inside of your mouth. The
doctor will also count and measure any red or white patches on the inside of your mouth. If
you have multiple lesions in your mouth, each lesion may be biopsied at this time. This will
be used to find out if you have cells that might become cancerous and will be studied to
look for certain genetic "markers" that may help researchers determine your eligibility for
this study. Biopsies will be taken under local anesthesia (an injection into the area to
numb it). The injection takes a couple of minutes to work and means that the biopsy itself
will be painless. The doctor will use a small instrument with a sharp end (like a
cookie-cutter) to remove the tissue. The biopsy will be about as small as the end of a
pencil eraser. Once the tissue has been removed, the doctor will clean the area with
sterile gauze and apply a topical (surface) medication. The whole process (local anesthetic
injection and biopsy) usually takes no more than 15 minutes from start to finish. When the
local anesthetic wears off after a few hours, there is relatively little pain or swelling.
Do not eat anything until the anesthetic wears off.

Your biopsy sample(s) will be sent to the laboratory for testing. It will take several days
to complete the testing before researchers will be able to tell you if you can take part in
this study.If it is found that you have cells in your mouth that may develop into cancer and
contain the selected genetic marker(s), you will be re-contacted by phone and asked if you
would like to participate in this study. If your cells are not this type, you will be
re-contacted and informed that you are not eligible to participate in this study.

If you agree to participate in this study, you will have some additional screening tests
performed. You will have blood (about 2 teaspoons) drawn for routine tests, to check your
liver function (about 1-2 teaspoons), and for research testing and to measure the level of
study drug in the body (about 4 tablespoons). You will participate in a 90-minute interview
discussing your demographics (such as age and race), smoking and alcohol usage, and
nutrition. Women who are able to have children must have a negative blood (about 1 teaspoon)
pregnancy test before receiving the study drug.

If you are found to be eligible to participate in the study, you will be randomly assigned
(as in the toss of a coin) to receive either erlotinib hydrochloride or placebo. A placebo
is a substance that looks like the study drug but has no active ingredients. Neither you
nor the investigators will know which treatment group you have been assigned to. However, in
the event of a medical emergency, the study chair can find out which group you are in, if
necessary. You can be informed which of the groups you were assigned to, after the study has
ended. There is no certainty that you will have an effect from the treatment, or if you will
be placed in a group with the active study drug.

While on study, you will take the study dose (either erlotinib hydrochloride or placebo) by
mouth, in tablet form, once a day. Tablets should be taken in the morning 1 hour before or
2 hours after a meal, other medications, vitamins, and iron supplements, with no more than
7 ounces of water. You should take the study dose around the same time every day. Every
attempt should be made to keep from vomiting the dose, for at least 30 minutes after taking
it. For example, if you feel nauseated before or after taking the study dose, anti-nausea
medications should be used. If you vomit after taking the study dose, the dose can be taken
again only if the tablet(s) can actually be seen and counted (in other words, they have not
dissolved yet). You will need to note the time you take each dose of medication throughout
the study on a calendar that the study nurse will give to you.

At Months 1, 3, 6, 9, and 12, you will return to clinic. You will have a physical exam
including measurement of vital signs. You will have a careful examination of the inside of
your mouth.You will have blood (about 2 teaspoons) drawn for routine tests and to check your
liver function (about 1-2 teaspoons). At Months 3, 6, and 12, you will have blood (about 2
teaspoons) drawn for research testing and to measure the level of study drug in the body.

Your study doctor will ask you about any medications you are taking, how you are feeling
(symptoms), and your current smoking and alcohol usage.

The nurse or study coordinator will collect the medication you did not take, as well as your
completed pill diaries, at every clinic visit. At Months 1, 3, 6, and 9, you will also be
given new study medication and pill diaries.

You may also have another small biopsy performed from the inside of your mouth in the area
where the cells that might become cancerous are located. The biopsy will be performed by
your doctor and will be sent to a lab for testing. At months 3 and 12, the doctor will also
count and measure any red or white patches on the inside of your mouth. Biopsies will be
taken after 3 months of treatment and at the end of 12 months of treatment. The tissue will
be tested to see if there are any cells that might become cancerous.

Following the end of treatment, you will return to the clinic every 6 months for 2 years.
You will have a complete physical exam, including measurement of vital signs. You will have
a careful examination of the inside of your mouth. You will have blood drawn (about 2
teaspoons) for routine tests, to check your liver function, and for research testing. Your
study doctor will ask you about any medications you are taking and how you are feeling
(symptoms), and your current tobacco and alcohol use.

In addition, at the final clinic visit, you will also take part in a personal interview.
During the interview, you will be asked questions regarding socio-demographic information
(such as age and race), nutrition habits, current and earlier tobacco use, alcohol use
habits, family history of cancer, use of medications, and how you are feeling. The interview
will take about 90 minutes to complete. The purpose of the interview is to collect
information to learn if there is a relationship between certain factors and your risk of
developing cancer of the mouth. You may be contacted in the future in order to collect more
information.

You may be taken off study if you are not able to follow the doctors' instructions, serious
side effects occur, or the doctor thinks it is in your best interest to leave the study. If
you are taken off study for any reason, you will be asked to return to the clinic for a
final clinic visit, preferably within 14 days after leaving the study.

This is an investigational study. Erlotinib hydrochloride is approved by the FDA for
treatment of NSCLC. Its use in this study is considered investigational. Up to 150
patients will take part in this multicenter study. Up to 90 will be enrolled at M. D.
Anderson.