Bortezomib With or Without Hormone Therapy in Treating Patients With Relapsed Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
VELCADE® (Bortezomib) for Injection Therapy for Early Relapsed Prostate Cancer

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Drug: Velcade
* Drug: LH-RH Agonist
* Drug: Androgen Receptor Antagonists


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate Relapsed disease after definitive local therapy, as documented only by a rise in prostate-specific antigen (PSA) Experienced PSA relapse after definitive local therapy 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 ≥ 4 weeks apart) The first of these two PSA values must rise above a previously recorded post-therapy nadir value Ineligible for curative therapy 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 28 days 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 At least 6 months since prior hormonal therapy combined with radiation therapy as definitive therapy Neoadjuvant hormonal therapy prior to definitive therapy (e.g., surgery, radiation therapy, brachytherapy, or cryoablation) allowed 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Velcade<br>Patient will complete Part A (Velcade only). If the patient has a complete response, he will come off study. If the patient has progressive disease, he will start Part B (Velcade + antiandrogen). If the patient has a partial response or stable disease, he will start Part B after at least a 7-day break. | Drug: Velcade<br>* Part A: 1.3 mg/m2 administered on days 1, 4, 8 and 11 followed by 10 days rest. A second cycle will be given at the same schedule. Cycle 3 will include 3 weekly injections. Part B: 1.3mg/m2 administered weekly for 3 weeks followed by 1 week break<br>* Other names: bortezomib;|
| Experimental: Part B: Velcade+LH-RH antagonist+Androgen receptor antagonist<br>Patient will start Part B after completing Part A or may be enrolled to part B only. | Drug: Velcade<br>* Part A: 1.3 mg/m2 administered on days 1, 4, 8 and 11 followed by 10 days rest. A second cycle will be given at the same schedule. Cycle 3 will include 3 weekly injections. Part B: 1.3mg/m2 administered weekly for 3 weeks followed by 1 week break<br>* Other names: bortezomib;Drug: LH-RH Agonist<br>* given as a 3 month depo-injection<br>Drug: Androgen Receptor Antagonists<br>* given orally daily for 3 months<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prostate-specific Antigen (PSA) Response |  | 3 months after the start of treatment | 
| Time to PSA Progression | PSA progression is defined as a PSA increase of 50% over the nadir CR or CR/PR value on three successive PSA measurements two months apart to a value of >= 1.0 ng/ml. | From on study until time of PSA progression for up to two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Experienced an Adverse Event by CTCAE v. 2.0 |  | From start of treatment until end of study, up to 6 months | 
| Disease-free Interval | This will only be analyzed if sample size warrants the analysis. | 3 months after combined treatment | 

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