This trial is active, not recruiting.

Condition oral cancer
Treatments erlotinib, placebo
Phase phase 3
Target EGFR
Sponsor M.D. Anderson Cancer Center
Collaborator National Cancer Institute (NCI)
Start date November 2006
End date November 2017
Trial size 150 participants
Trial identifier NCT00402779, 2003-0824, EPOC, NCI-2009-00873, P01CA106451



This study will test the ability of an epidermal growth factor receptor (EGFR) inhibitor (erlotinib) to reduce the incidence of oral cancer in the high-risk setting of oral leukoplakia with LOH in two cohorts, oral IEN (Intraepithelial neoplasia) patients with LOH in 3p and/or 9p and one other specific chromosomal locus but without cancer or oral IEN patients with LOH in 3p and/or 9p associated with curatively treated oral cancer. Researchers will test this treatment in a randomized clinical trial with 2 treatment arms: Erlotinib 150mg orally each day or placebo.

Primary Aim:

The primary endpoint of the trial will be the oral cancer-free survival in patients receiving erlotinib as compared with the control or placebo group.

Secondary Aims:

1. The size, number, and appearance of oral IEN will be assessed and correlated with cancer risk. A > 50% reduction in the bidimensional measurements of IEN lesions is considered a treatment response. Researchers hypothesize that patients with IEN lesions and loss of heterozygosity (LOH) of the oral cavity will respond to erlotinib.

2. To examine toxicity associated with erlotinib. Researchers hypothesis that patients with oral lesions will tolerate treatment with erlotinib.

3. To assess a panel of molecular markers for correlations with oral cancer development in oral IEN patients.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose prevention
Balanced randomization: Erlotinib 150 mg continuous administration for 1 year.
erlotinib Tarceva
150 mg by mouth daily
(Placebo Comparator)
Balanced randomization: Placebo continuous administration for 1 year.
Tablet by mouth daily

Primary Outcomes

Oral cancer-free survival
time frame: 3 Months

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title Erlotinib Prevention of Oral Cancer (EPOC)
Principal investigator Vassiliki Papadimitrakopoulou, M.D.
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by M.D. Anderson Cancer Center.