Docetaxel and Erlotinib in Treating Older Patients With Prostate Cancer

OBJECTIVES:

Primary

- Determine the response rate and response duration in older patients with progressive
hormone refractory prostate cancer treated with docetaxel and erlotinib.

Secondary

- Determine the safety of this regimen in these patients.

- Evaluate the quality of life of patients treated with this regimen.

OUTLINE: This is a multicenter study.

- Initial combination therapy: Patients receive docetaxel IV over 1 hour on day 1 and
oral erlotinib once daily on days 1-21. Treatment repeats every 21 days for up to 9
courses in the absence of disease progression or unacceptable toxicity. Patients with
responding disease receive 3 additional courses beyond maximal response.

- Extension phase: After 9 courses of initial combination therapy, patients achieving a
complete response, partial response, or stable disease receive 8 courses of erlotinib
alone (total of 17 courses of study treatment).

Quality of life is assessed at baseline, day 1 of each course, and at the end of study
treatment. For patients in the extension phase, quality of life is also assessed on day 1 of
courses 10, 12, 14, and 16.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 22 patients will be accrued for this study within 24 months.

Inclusion Criteria

- Histologically confirmed adenocarcinoma of the prostate.

- Disease progression following primary or secondary hormonal therapy.

- All patients must be maintained on GnRH analog during this study.

- Serum PSA must be > 20 ng/mL in patients without bidimensionally measurable disease
or bone disease.

- Age > 65 years.

- Karnofsky performance status of > 70%.

- Life Expectancy of > 12 weeks.

- Peripheral neuropathy, if present must be < grade 1 by NCI criteria.

- Radionuclide bone scan and chest /abdominal/pelvic CT scan must be obtained in all
patients within 4 weeks prior to cycle 1/day 1.

- Sexually active men must be willing to consent to using effective contraception while
on treatment and for 6 months following treatment.

- No concomitant use of prostata or saw palmetto.

- Testosterone must be castrate levels(< 50 ng/ml).

- WBC > 2.8 x 109/L

- Granulocytes > 1.5 x 109/L

- Platelets > 100 x 109/L

- Hemoglobin > 8.0 g/dL

- Serum creatinine < 2.1

- Total bilirubin < ULN

- Alkaline Phosphatase < 2.5 ULN AND ALT/AST < 2.0 ULN OR Alkaline Phosphatase 2.6-3.9
ULN, AND ALT/AST <1.5 ULN OR Patients with known bone involvement may be included
with alkaline phosphatase > 4.0 ULN, IF ALT and AST and total bilirubin are within
the normal range and the bone involvement is thought to account for elevated alkaline
phosphatase.

- PT, INR should be within physiologic limits, i.e. INR 0.7 - 1.5. If patient is
receiving anticoagulation therapy then INR should be within the range of 2.0 - 3.5.

Exclusion Criteria

- Any major surgery or radiotherapy, within 4 weeks prior to cycle 1/day 1 (within 12
weeks for previous treatment with strontium-89, rhenium, or sumarium).

- Hormonal therapy, with the exception of androgen deprivation therapy and stable
regimens of prednisone and dexamethasone, (no change within 2 weeks prior to
cycle1/day 1). Prior prostate hormonal treatment must have been discontinued at least
four weeks (6 weeks for Casodex) prior to cycle1/day 1.

- Cardiovascular: Uncontrolled hypertension (resting blood pressure >160/100 mm/Hg);
clinical episodes of congestive heart failure, angina pectoris, or myocardial
infarction within the last year.

- Any active infections (requiring IV antibiotics).

- Any prior chemotherapy.

- Not reliable for adequate follow-up.

- History of severe hypersensitivity reaction to drugs formulated with polysorbate 80.

- Brain metastases or (clinical signs of) brain involvement or leptomeningeal disease.

- Patients with a history of another malignancy during the last 5 years other than
prostate cancer, nonmelanomatous skin cancer or in situ bladder cancer (Stage T1a).

- Concurrent commercial or investigational antineoplastic therapy.