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.

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. Approximately 491
patients will be screened for this study. Up to 120 will be enrolled at MD Anderson.

Inclusion Criteria:

1. Male or female patients with one of the following: (a) loss of heterozygosity (LOH) at
3p14 and/or 9p21 in the oral IEN of patients with a history of curatively treated oral
cancer or (b) LOH at 3p14 and/or 9p21 plus at one other chromosomal region in the IEN
of patients with no oral cancer history.

2. Participants must have confirmed diagnosis of oral IEN lesion with LOH. (Note:The
initial screening biopsy of oral IEN lesion with LOH must be obtained within 12 months
of study enrollment. If initial diagnostic biopsy for LOH is > 3 months prior to study
enrollment, investigators may use clinical judgment to order an additional screening
biopsy to assess histopathological changes).

3. Age >/= 18 years

4. ECOG performance status <2

5. Participants must have normal organ & marrow function as defined below w/in 30 days of
randomization:CBC w/ differential white cell count-acceptable results must include:WBC
>3,000ul, hemoglobin>10 g/dl, platelet count > 125,000ul, LFTs-total bilirubin &
alkaline phosphatase, AST (SGOT) & ALT (SPGT) all w/in <1.5xULN.Note:At the discretion
of the attending physician,participants w/ Gilbert's disease may still be eligible to
participate in the event the total bilirubin value is >1.5xULN. Kidney function-serum
creatinine< 1.5xULN Chemistry-Sodium & potassium all w/in normal institutional limits.

6. The effects of the study agent on the developing human fetus are unknown.For this
reason,WOCBP & men must agree to use adequate contraception (hormonal or barrier
method of birth control;abstinence)prior to study entry& for the duration of active
treatment.Neg.serum pregnancy test in WOCBP.Childbearing potential will be defined as
women who have had menses w/in the past 12 mths,who have not had tubal ligation or
bilateral oophorectomy.Should a woman become pregnant or suspect she is pregnant while
participating in this study,she should inform her study physician immediately

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

Exclusion Criteria:

1. Patients with active cancer or any cancer within the previous two years, excluding
oral and non-melanoma skin cancer.

2. Patients with acute intercurrent illness or who have had surgery, radiation therapy,
or chemotherapy within the preceding 4 weeks unless they have fully recovered.

3. Patients with a documented history of coagulopathy and/or those taking warfarin or
warfarin-derivative anticoagulants

4. Women who are pregnant (confirmed by b-HCG if applicable) or breastfeeding

5. Any medical or psychological condition or any reason that, according to the
investigator's judgment, makes the patient unsuitable for participation in the study

6. Patients who have participated in other experimental therapy studies within 3 months
of enrollment to this trial

7. Patients with a history of inflammatory bowel disease

8. Patients with a documented history of interstitial lung disease