Radiation Therapy, Docetaxel, and Hormone Therapy in High-Risk Locally Advanced Metastasized Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Specialized radiation therapy that delivers a high- dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as goserelin and bicalutamide, may lessen the amount of androgens made by the body. Giving radiation therapy together with chemotherapy and hormone therapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of docetaxel when given together with intensity-modulated radiation therapy and hormone therapy in treating patients with high-risk locally advanced prostate cancer with pelvic lymph node metastasis.

Detailed Description
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OBJECTIVES: Primary Determine, preliminarily, the grade III or IV toxicity rate of concurrent extended-field intensity-modulated radiotherapy (IMRT), docetaxel, and androgen deprivation therapy in patients with high-risk, locally advanced prostate cancer with pelvic lymph node metastasis. Secondary Determine, preliminarily, the progression-free survival of patients treated with this regimen. Determine the maximum tolerated dose of docetaxel when administered with concurrent IMRT in this patients. OUTLINE: This is a dose-escalation study of docetaxel. Patients receive combined androgen deprivation therapy (if not already on combined hormonal therapy) comprising goserelin acetate* subcutaneously once every 3 months for up to 2 years and oral bicalutamide once daily beginning on day 1 and continuing until the completion of radiotherapy. Beginning at approximately week 9 of androgen deprivation therapy, patients receive docetaxel IV over 1 hour once weekly for up to 9 weeks. Concurrently with chemotherapy, patients undergo intensity-modulated radiotherapy 5 days a week for up to 45 fractions (9 weeks). Cohorts of 3-6 patients receive escalating doses of docetaxel 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. Note: *Not required for patients who have undergone bilateral orchiectomy After completion of study therapy, patients are followed periodically for 5 years.

Official Title
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Phase I Study Evaluating Extended Field Intensity Modulated Radiation Therapy and Docetaxel in Patients With Prostate Cancer Associated With Pelvic Node Metastasis

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: bicalutamide
* Drug: docetaxel
* Drug: goserelin
* Radiation: intensity-modulated radiation therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed adenocarcinoma of the prostate o Locally advanced disease (T1 -T3b, N1 or N2, M0) at high risk for recurrence Biopsy-proven pelvic lymph node involvement No T4 lesion Prior androgen suppression within the past 14 months is allowed provided the following criterion is met: o No biochemical evidence of PSA progression after androgen withdrawal 1. PSA progression, defined as 2 consecutive rising PSA values > 4.0 ng/mL taken ≥ 2 weeks apart Karnofsky performance status 80-100% absolute neutrophil count (ANC) ≥ 1,500/mm³ Hemoglobin ≥ 10 g/dL Platelet count > 100,000/mm³ Bilirubin normal Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment Meets 1 of the following criteria: Alkaline phosphatase (AP) normal and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 5 times upper limit of normal (ULN) AP ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN AP ≤ 5 times ULN AND AST or ALT normal Exclusion Criteria: No evidence of distant metastasis, including any of the following: Bone metastasis Pathologic or radiographic evidence of lymph node involvement above the L4 - L5 interspace No peripheral neuropathy > grade 1 No significant comorbidity that would preclude radiotherapy No other prior malignancy except nonmelanoma skin cancer or any other cancer for which the patient has been disease-free for the past 5 years No hypersensitivity to docetaxel or other drugs formulated with polysorbate 80 No history of Crohn's disease, ulcerative colitis, or irritable bowel syndrome No unrepaired inguinal hernia No prior pelvic or abdominal radiotherapy or prostate brachytherapy implant No prior prostatectomy No prior pelvic or abdominal surgery that resulted in excessive amounts of small intestine located within the pelvis No other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 120 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: Docetaxel, intensity-modulated radiation therapy and hormone therapy<br>This phase I trial is studying the side effects and best dose of docetaxel when given together with intensity-modulated radiation therapy and hormone therapy in treating patients with high-risk locally advanced prostate cancer with pelvic lymph node metastasis. | Drug: bicalutamide<br> <br> * Other names: Casodex;Drug: docetaxel<br> <br> * Other names: Docefrez, Taxotere;Drug: goserelin<br> <br> * Other names: Zoladex;Radiation: intensity-modulated radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity rate | Toxicity rate as assessed by NCI CTCAE v3.0 | during therapy and follow-up, & for 5 years after radiation is completed | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Time to Prostate Specific Antigen (PSA) failure | From start of therapy up to 5 years after radiation is complete | 
| Maximum tolerated dose (MTD) of docetaxel | Maximum tolerated dose (MTD) of docetaxel (dose below which excess dose limiting toxicity, DLT, observed.) If 3 patients treated at that dose, then added 3 should be entered, that process proceeds down, so MTD becomes highest dose where no more than 1 toxicity observed in 6 patients. | From start of therapy up to 5 years after radiation is complete | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I prostate cancer, stage II prostate cancer, stage III prostate cancer, stage IV prostate cancer, adenocarcinoma of the prostate, recurrent prostate cancer