Docetaxel and Erlotinib in Treating Older Patients With Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Combining docetaxel with erlotinib may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving docetaxel together with erlotinib works in treating older patients with progressive prostate cancer that has not responded to hormone therapy.

Detailed Description
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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.

Official Title
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Phase II Trial Of TAXOTERE + TARCEVA™ To Treat HRPC In Men ≥ 65 Years Of Age

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: docetaxel
* Drug: erlotinib hydrochloride


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Taxotere plus Tarceva<br>Patients receive Tarceva 150 mg daily for 21 consecutive days (one treatment cycle). In addition, all patients will receive single agent Taxotere 60 mg/m2 IV over 1 hour infusion every 21 ± 2 days and have it administered on day 1. Taxotere + Tarceva to be taken for three cycles past maximal response or until one of the following occurs: 1) a drug-related toxicity requiring discontinuation, 2) disease progression, or 3) for a maximum of 9 cycles. Upon completion of 9 cycles of Taxotere plus Tarceva, patients showing evidence of objective response (CR, PR or stable disease) may continue in the extension phase of the study and receive treatment with Tarceva alone. Treatment response evaluated after four cycles of Tarceva treatment(immediately prior to cycle 14). Patients with progression of disease will be taken off study. Responding and stable disease patients will remain on study for up to 8 extension-phase cycles for a total of 17 cycles. | Drug: docetaxel<br>* Administered as an IV infusion of 60m/m2 over a 1-hour period, once every 21 ± 2 days<br>* Other names: Taxotere;Drug: erlotinib hydrochloride<br>* Will be taken at a starting daily dose of 150mg<br>* Other names: Tarceva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response | During the primary phase of the study (cycles 1-9), response to the combination of Taxotere® and Tarceva™ treatment will be assessed at the end of every 3 treatment cycles (9 weeks) with the standard procedures such as physical examination, CT scans, bone scans, MRI and laboratory results. For those patients that continue on in the extension phase of the study (cycles 10 -17), response to Tarceva™ is to be assessed at the end of 4 treatment cycles (end of cycle 13). | 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability based on adverse events, laboratory tests and physical exams |  | 9 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, recurrent prostate cancer