RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Androgens can cause the growth of prostate cancer cells. Drugs, such as goserelin, leuprolide, flutamide, or bicalutamide, may stop the adrenal glands from making androgens. Giving bortezomib with hormone therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving bortezomib with or without hormone therapy works in treating patients with relapsed prostate cancer.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the prostate recurrent prostate cancer	Drug: bicalutamide  Drug: bortezomib  Drug: flutamide  Drug: goserelin  Drug: leuprolide  Procedure: antiandrogen therapy  Procedure: endocrine therapy  Procedure: enzyme inhibitor therapy  Procedure: hormone therapy  Procedure: releasing factor agonist therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the prostate-specific antigen (PSA) response in patients with early relapsed adenocarcinoma of the prostate treated with bortezomib.
• Determine time to PSA relapse in patients treated with this drug.

Secondary

• Determine the safety of this drug in combination with combined androgen blockade therapy in these patients.
• Determine the disease-free interval in patients treated with this regimen.

OUTLINE: This is a 2-part, open-label, multicenter study.

• Part A (bortezomib only): Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for 3 courses. Patients then receive bortezomib once weekly for 3 weeks. Patients achieving complete response, partial response, or stable disease are observed monthly for prostate-specific antigen (PSA) relapse. Patients with PSA progression during or after treatment with bortezomib proceed to part B.
• Part B (bortezomib and combined androgen blockade therapy): Patients receive androgen blockade therapy comprising a 3-month subcutaneous injection of goserelin OR leuprolide OR other FDA-approved method of primary androgen suppression AND oral flutamide or bicalutamide once daily for 3 months. Patients also receive bortezomib IV over 3-5 seconds on days 1, 8, and 15. Treatment with bortezomib repeats every 28 days for 3 courses. Patients with a PSA level of less than 0.2 ng/mL enter the follow-up phase of the study. Patients with a PSA level that has not dropped receive additional combined androgen blockade therapy and 3 additional courses of bortezomib as above. Patients are followed monthly for 1 year and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 21-42 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
• Relapsed disease after definitive radiotherapy or surgery, as documented only by a rise in prostate-specific antigen (PSA)*
• Rising PSA (≥ 1.0 ng/mL after nadir < 1.0 ng/mL)
• PSA increase of ≥ 0.3 ng/mL (increase occurred between 2 separate measurements taken ≥ 1 month apart)
• PSA increase ≥ 25% above the nadir for patients who received prior androgen ablation therapy for a previous PSA relapse NOTE: *PSA relapse must not have occurred while on androgen ablation therapy
• Ineligible for curative radiotherapy or surgery
• No clinical evidence of local recurrence (i.e., palpable induration or mass in the prostatic fossa) other than PSA elevation
• No evidence of palpable disease in the prostatic bed
• No metastatic disease (M0)
• No non-nodal (> N1) metastasis
• No evidence of osseous metastasis on bone scan within the past month

PATIENT CHARACTERISTICS: Age

• Over 18

Performance status

• ECOG 0-1

Life expectancy

• At least 1 year

Hematopoietic

• Platelet count ≥ 30,000/mm^3
• Absolute neutrophil count ≥ 1,000/mm^3

Hepatic

• No known hepatitis B or C positivity

Renal

• Creatinine clearance ≥ 30 mL/min

Immunologic

• No known human T-cell lymphotropic virus positivity
• No hypersensitivity to bortezomib, boron, or mannitol
• No known HIV 1 or 2 positivity
• No active, ongoing bacterial, viral, or fungal infection

Other

• Fertile patients must use effective contraception
• No peripheral neuropathy ≥ grade 2
• No other disease, condition, or social or geographic constraint that would preclude study participation
• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• No concurrent chemotherapy

Endocrine therapy

• See Disease Characteristics
• No prior hormonal therapy
• No other concurrent hormonal therapy

Radiotherapy

• See Disease Characteristics
• More than 12 months since prior radioactive seed therapy
• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• More than 4 weeks since prior surgery
• No concurrent surgery

Other

• No concurrent second-line herbal preparations, including PC-SPES
• No other concurrent investigational agents

California
      Loma Linda University Cancer Institute at Loma Linda University Medical Center, Loma Linda,  California,  92354,  United States; Recruiting
Colorado
      University of Colorado Cancer Center at University of Colorado Health Sciences Center, Denver,  Colorado,  80262,  United States; Recruiting
South Carolina
      Hollings Cancer Center at Medical University of South Carolina, Charleston,  South Carolina,  29425,  United States; Recruiting

Study chairs or principal investigators

Andrew S. Kraft, MD,  Principal Investigator,  Medical University of South Carolina   

Study ID Numbers:  CDR0000406013; MUSC-031218; MUSC-HR-11357; NCT00103376
Record last reviewed:  January 2005
Last Updated:  February 15, 2005
Record first received:  February 7, 2005
ClinicalTrials.gov Identifier:  NCT00103376
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08