Docetaxel and Erlotinib in Treating Patients With Advanced Non-Small Cell Lung Cancer or Other Solid Tumors

OBJECTIVES:

Primary

- Determine the safety and feasibility of two different schedules of erlotinib
hydrochloride and docetaxel in patients with advanced solid tumors. (Phase I [completed
as of 12/01/2004])

- Determine the response rate in patients with advanced non-small cell lung cancer treated
with second-line docetaxel and erlotinib hydrochloride. (Phase II)

Secondary

- Compare the toxicity of two different schedules of erlotinib hydrochloride and docetaxel
in these patients. (Phase I [completed as of 12/01/2004])

- Determine the maximum tolerated dose of two different schedules of erlotinib
hydrochloride and docetaxel. (Phase I [completed as of 12/01/2004])

- Assess the overall survival and progression-free survival. (Phase II)

- Determine the frequency and severity of toxicities associated with this treatment
regimen. (Phase II)

Tertiary

- Perform laboratory correlative studies on patient tissue and blood samples to
investigate potential predictors of response.

OUTLINE: This is a phase I, dose-escalation study of erlotinib hydrochloride (phase I
completed as of 12/01/2004) followed by a phase II, open-label study.

- Phase I (completed as of 12/01/2004): Patients will be assigned in alternating fashion
to 1 of 2 treatment groups.

- Group I: Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib
hydrochloride once on days 2, 9, and 16.

- Group II: Patients receive docetaxel as in group I and oral erlotinib hydrochloride
once daily on days 2-16.

In both groups, treatment repeats every 21 days for up to 6 courses in the absence of
unacceptable toxicity or disease progression. Patients may then continue to receive erlotinib
hydrochloride alone in the absence of unacceptable toxicity or disease progression.

In both groups, cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride
until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

- Phase II: Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib
hydrochloride at the MTD determined in group II of phase I once daily on days 2-16.
Treatment repeats every 21 days for up to 6 courses in the absence of disease
progression or unacceptable toxicity. Patients may then continue to receive erlotinib
hydrochloride alone in the absence of disease progression or unacceptable toxicity.

Blood samples, buccal mucosal cells, and tumor tissue are obtained before and after
treatment. Epidermal growth factor receptor (EGFR) expression and polymorphisms and p27
protein expression are assessed by immunohistochemistry. Immunofluorescence (by
laser-scanning cytometry) is used to detect EGFR and p27.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 87 patients will be accrued for this study.

Inclusion Criteria:

- For the phase II portion patients must have cytologically or histologically proven
NSCLC. (Completed 12/1/04 - For the phase I portion of the study patients must have
cytologically or histologically proven advanced solid tumors for which there is no
standard therapy of curative intent).

- For the phase II portion patients must have disease that has progressed or recurred
after treatment with platinum based therapy. Patients that have stable disease after
front line platinum based therapy is also eligible.

- No more than 1 previous treatment for metastatic disease is allowed for the phase II
portion. (Completed 12/1/04 - Any number of prior chemotherapy regimens for metastatic
disease are allowed for the phase I portion).

- Patients must have measurable disease by RECIST criteria. Disease in previously
irradiated sites is considered measurable if there is clear disease progression
following radiation therapy. (Completed 12/1/04 - Patients with evaluable disease may
be included in the phase I portion of the trial.

- Patients must be 18 years of age or older.

- Patients must have a performance status of 0-1 for the phase II portion of the trial.
(Completed 12/1/04 - performance status of 0-2 for is allowed for the phase I portion
of study

- Patients must have an estimated survival of at least 3 months.

- Any prior chemotherapy that patients have received has to have been completed at least
4 weeks prior to start of OSI-774/Docetaxel. For prior mitomycin chemotherapy a 6-week
interval is required. Prior radiation must have been completed at least 2 weeks prior
to start of therapy. All side effects must have resolved prior to start of
OSI-774/Docetaxel.

- Patients must have adequate renal function as documented by a serum creatinine < 1.5
mg/dl or a calculated creatinine clearance of > 50 ml/min (see appendix for formula
for calculating creatinine clearance).

- Patients must have adequate liver function as documented by serum bilirubin < ULN. AST
must be < 2.5 x institutional upper limit of normal.

- Patients must have a pretreatment granulocyte count of >1500/mm3 and platelet count of
>100 000/mm3.

- Patients with asymptomatic treated brain metastasis (surgical resection or
radiotherapy) may be included if they are neurologically stable and have been off
steroids and anticonvulsants for at least 4 weeks. Because of the possibility of
treatment related neurological toxicity it is difficult to evaluate for toxicity in
the presence of symptomatic brain metastasis.

- All patients must give written informed consent.

- Able to take and retain oral medication.

- Patients of reproductive potential must agree to use effective contraceptive method
while on treatment and for 3 months afterwards as the effects of these drugs on the
unborn fetus are unknown.

- Patients on Coumadin should have their INR monitored at least once per week or more
frequently depending on the investigators judgment. There have been some case reports
of increased INR when Coumadin is co-administered with OSI-774/placebo.

Exclusion Criteria:

- May not have previously received docetaxel; OSI-774 or any prior EGFR targeted
therapy.

- Females can not be pregnant or breastfeeding as the effects of these drugs on the
unborn fetus are unknown. Documentation of a negative pregnancy test is required for
all women of reproductive potential.

- Patients with symptomatic brain metastasis or still requiring steroids may not be
included.

- Clinically significant ophthalmologic abnormalities will be excluded. This includes
severe dry eye syndrome, keratoconjunctivitis sicca, Sjogren's syndrome, severe
exposure keratopathy, or other disorders that might increase the risk of corneal
epithelial injury.

- A history of severe hypersensitivity reaction to docetaxel or other drugs formulated
with polysorbate 80.

- Pre-existing neuropathy > grade 2 may not participate

- No other prior malignancy is allowed for the phase II portion except for the
following: adequately treated basal cell or squamous cell skin cancer, in situ
cervical cancer, adequately treated stage I or II cancer from which the patient is
currently in complete remission, or any other cancer from which the patient has been
disease-free for over five years.