OSI-774/Cisplatin/Taxotere in Head & Neck Squamous Cell Cancer

OSI-774 is a drug that helps to block the activity of an enzyme that is believed to play an
important role in cell growth. It is hoped that blocking these enzymes will slow tumor
growth. Both cisplatin and docetaxel are commonly used chemotherapy drugs. These drugs are
designed to target and destroy cancer cells.

Before the study, you will have a physical exam, blood tests (around 2 teaspoons), and an
electrocardiogram (ECG - a test that measures the electrical activity of the heart). You will
also have a chest x-ray and a CT scan. If the diagnosis has not yet been confirmed, a biopsy
of the tumor may need to be done. Women who are able to have children must have a negative
blood or urine pregnancy test.

During treatment, you will take OSI-774 by mouth once a day. Once every 3 weeks, you will be
given docetaxel and cisplatin. Docetaxel is given by a continuous infusion into a vein over 1
hour. This will be followed by an infusion into a vein of cisplatin over 2 hours. Treatment
with docetaxel and cisplatin is given every 3 weeks for 18 weeks. You will continue to take
OSI-774 until your disease worsens, until side effects become too severe, or until your
doctor thinks it is no longer benefiting you.

If at any time during the study the disease becomes worse or you experience any intolerable
side effects, you will be taken off the study and your doctor will discuss other treatment
options with you.

During the study, you will have blood drawn (around 2 teaspoons) once a week. These samples
will be used for routine lab tests. Every 3 weeks, you will have a physical exam and your
vital signs and weight will be measured. You will also be asked about any side effects you
may be experiencing. If your doctor feels it is necessary, you may have more frequent
check-up visits.

Every 6 weeks during treatment, you will have blood tests (around 2 teaspoons), and imaging
tests. The imaging tests include a chest x-ray and a CT scan of the head and neck area. You
may also have CT scans of other areas of the body. These tests are being done to check on the
status of the disease.

You may continue receiving OSI-774 for as long as your cancer responds to study treatment. If
you continue to receive OSI-774, every 3 months you will have a physical exam (including
measurement of vital signs), routine blood tests (about 2 teaspoons), a performance status
test (a test looking at the ability to perform everyday activities), a chest x-ray, and a CT
or MRI scan. Your doctor may decide to take you off this study if you experience significant
side effects or your medical condition worsens.

This is an investigational study. OSI-774 is approved by the FDA for treatment of NSCLC in
patients who have relapsed. Its use in this study is considered investigational. Docetaxel
and cisplatin are FDA approved and commercially available. There will be a total of 50
patients taking part in this study. There will be no cost for OSI-774 or for any tests and
procedures performed solely for this research study.

Inclusion Criteria:

1. Have histologically or cytologically confirmed metastatic or recurrent head and neck
squamous cell carcinoma from the primary lesion and/or lymph nodes of the oral cavity,
oropharynx, hypopharynx, or larynx.

2. Have measurable disease, defined as at least one lesion that can be accurately
measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with
conventional techniques or as >= 10 mm with spiral CT scan. See section 9.2 for the
evaluation of measurable disease.

3. Have not received any prior systemic chemotherapy for metastatic or recurrent head and
neck squamous cell carcinoma. If patients have received prior combined modality
therapy, they must be off therapy for at least 6 months.

4. Be >= 18 years of age.

5. No acute intercurrent illness or infection.

6. ECOG performance status =<2 (Karnofsky =>60%). Have normal organ and marrow function
defined as: leukocytes=>3,000/uL; absolute neutrophil count=>1,500/uL; platelets
=>100,000/uL hemoglobin >= 8g/dl; total bilirubin within normal institutional limits;
AST(SGOT)/ALT(SGPT) =<2.5 X institutional upper limit of normal if alkaline phosphate
is creatinine =<2.0 xULN OR creatinine clearance >60 mL/min/1.73 m**2 for patients with
creatinine levels above institutional normal

7. The effects of OSI-774 on the developing human fetus at the recommended therapeutic
dose are unknown. For this reason, 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, for the duration of study participation, and for 3 months after the
completion of therapy. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately.

8. History of non-melanoma skin cancer, or other malignancies treated 5 years or more
prior to the current tumor, from which the patient has remained continually
disease-free, are eligible.

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

10. Inclusion of women and minorities. Both men and women and members of all ethnic groups
are eligible for this trial. The proposed study population will consist of patients of
all ethnic backgrounds and either gender, treated at MD Anderson Cancer Center in
Houston, Texas.

Exclusion Criteria:

1. Patients who have had chemotherapy or non-palliative radiotherapy for their recurrent
or metastatic head and neck cancer.

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

3. Brain metastases should be excluded from this clinical trial because of their poor
prognosis and because they often develop progressive neurologic dysfunction that would
confound the evaluation of neurologic and other adverse events.

4. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to OSI-774 or other agents used in the study.

5. Patient has received prior biologic therapy targeting EGFR.

6. Signs or symptoms of acute infection requiring systemic therapy.

7. Exhibits confusion, disorientation, or has a history of major psychiatric illness that
may impair patient's understanding of the informed consent.

8. Requires total parenteral nutrition with lipids.

9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

10. Histology other than squamous cell carcinoma.

11. Refusing to sign the informed consent.

12. History of severe hypersensitivity reaction to Taxotere®.

13. Pre-existing peripheral neuropathy NCI CTC grade 2 or worse.

14. Pregnant or lactating women are excluded from this study because OSI-774 is an unknown
Class agent with the potential for teratogenic or abortifacient effects. Because there
is an unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with OSI-774, breastfeeding should be discontinued if the
mother is treated with OSI-774. These potential risks may also apply to other agents
used in this study.

15. Because patients with immune deficiency are at increased risk of lethal infections
when treated with marrow-suppressive therapy, HIV-positive patients receiving
combination anti-retroviral therapy are excluded from the study because of possible
pharmacokinetic interactions with OSI-774, cisplatin, or docetaxel or other agents
administered during the study. Appropriate studies will be undertaken in patients
receiving combination anti-retroviral therapy when indicated.