RATIONALE: 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. Radiation therapy uses high energy x-rays to kill tumor cells. Docetaxel may also make tumor cells more sensitive to radiation therapy. Androgens can cause the growth of prostate cancer cells. Drugs, such as leuprolide, goserelin, or bicalutamide, may stop the adrenal glands from making androgens. Giving chemotherapy with radiation therapy 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 with radiation therapy and hormone therapy in patients with locally advanced prostate cancer.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the prostate stage II prostate cancer stage III prostate cancer stage IV prostate cancer	Drug: bicalutamide  Drug: docetaxel  Drug: goserelin  Drug: leuprolide  Procedure: adjuvant therapy  Procedure: antiandrogen therapy  Procedure: chemotherapy  Procedure: endocrine therapy  Procedure: hormone therapy  Procedure: neoadjuvant therapy  Procedure: radiation therapy  Procedure: radiosensitization  Procedure: releasing factor agonist therapy	Phase I

Further Study Details: 

OBJECTIVES: Primary

• Determine the maximum tolerated dose of docetaxel, when given in combination with radiotherapy and hormonal therapy, in patients with high-risk clinically locally advanced prostate cancer.

Secondary

• Determine progression-free survival and time to prostate-specific antigen failure in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of docetaxel.

Patients receive goserelin subcutaneously (SC) OR leuprolide intramuscularly (IM) once monthly AND oral bicalutamide once daily for 2 months. Patients then receive docetaxel IV over 30 minutes on days 1, 8, 15, 22, 29, 36, 43, 50, and 57. Concurrent with chemotherapy, patients undergo radiotherapy on days 1-5 weekly for 8.6 weeks (43 fractions). Patients continue to receive goserelin SC OR leuprolide IM once monthly during chemotherapy and radiotherapy and then every 3 months for 2 years. Treatment continues in the absence of disease progression or unacceptable toxicity.

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.

Patients are followed every 3 months for 2 years, every 6 months for 4 years, and then annually therafter.

PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate
• Clinically locally advanced disease, defined as 1 of the following:
• T_xN_0M_0 AND prostate-specific antigen (PSA) ≥ 20 ng/mL AND Gleason score ≥ 7
• T_3b,4N_0M_0 AND any PSA and Gleason score
• T_xN_0M_0 AND any PSA AND Gleason score ≥ 8
• No pelvic lymph node disease that would necessitate pelvic radiotherapy
• No radiologic evidence of metastatic disease on bone scan or on CT scan or MRI of the abdomen or pelvis

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin normal
• Meets 1 of the following criteria:
• AST or ALT ≤ 5 times upper limit of normal (ULN) AND alkaline phosphatase ≤ ULN
• AST or ALT ≤ 1.5 times ULN AND alkaline phosphatase ≤ 2.5 times ULN
• AST or ALT ≤ ULN AND alkaline phosphatase ≤ 5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No uncontrolled cardiac disease

Other

• Fertile patients must use effective contraception during and for 3 months after study participation
• HIV negative
• No peripheral neuropathy > grade 1
• No uncontrolled infection
• No uncontrolled diabetes mellitus
• No psychiatric illness that would preclude patient from giving informed consent
• No history of severe hypersensitivity reaction to docetaxel or other drugs formulated with Polysorbate 80

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior immunotherapy for prostate cancer
• No concurrent sargramostim (GM-CSF) or filgrastim (G-CSF)

Chemotherapy

• No prior chemotherapy for prostate cancer
• No other concurrent chemotherapy

Endocrine therapy

• Prior androgen deprivation therapy allowed for up to 4 weeks before study entry
• No concurrent hormone therapy except for the following:
• Steroids for adrenal insufficiency
• Hormones for non-disease-related conditions (e.g., insulin for diabetes)
• Intermittent dexamethasone as an antiemetic or as premedication for docetaxel administration

Radiotherapy

• No prior radiotherapy for prostate cancer
• No concurrent radiotherapy, including palliative radiotherapy

Surgery

• At least 4 weeks since prior major surgery

Other

• No prior alternative therapy for prostate cancer

South Carolina
      Hollings Cancer Center at Medical University of South Carolina, Charleston,  South Carolina,  29425-2225,  United States; Recruiting

Study chairs or principal investigators

Uzair B. Chaudhary, MD,  Study Chair,  Medical University of South Carolina   

Study ID Numbers:  CDR0000387959; MUSC-100783; MUSC-HR-11326; AVENTIS-MUSC-100783; NCT00099086
Record last reviewed:  November 2004
Last Updated:  February 4, 2005
Record first received:  December 8, 2004
ClinicalTrials.gov Identifier:  NCT00099086
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08