Hormone Therapy With or Without Squalamine Lactate in Treating Patients Who Are Undergoing a Radical Prostatectomy for Locally Advanced Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Androgens can cause the growth of prostate cancer cells. Drugs, such as leuprolide and bicalutamide, may stop the adrenal glands from making androgens. Squalamine lactate may stop the growth of prostate cancer by blocking blood flow to the tumor. Giving hormone therapy together with squalamine lactate before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This randomized phase II trial is studying how well giving hormone therapy together with squalamine lactate works compared to hormone therapy alone in treating patients who are undergoing a radical prostatectomy for locally advanced prostate cancer.

Detailed Description
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OBJECTIVES: Compare the effect of neoadjuvant androgen-ablation therapy with vs without squalamine lactate on induced tumor regression and grade migration in patients with locally advanced high-risk adenocarcinoma of the prostate undergoing a radical prostatectomy. Compare the duration of clinical disease-free survival of patients treated with these regimens. Determine the applicability of prostate-specific antigen (PSA) serology as an endpoint determinant in patients treated with these regimens. Compare the feasibility and potential safety effects on wound healing and recovery in patients treated with these regimens before and after a radical prostatectomy. OUTLINE: This is an open-label, randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive leuprolide intramuscularly once a month for 3 months and oral bicalutamide once a day for 2 weeks. Arm II: Patients receive leuprolide and bicalutamide as in arm I plus squalamine lactate IV over 4 hours once weekly for 6 weeks. Seven weeks after beginning treatment, patients in both arms undergo standard radical prostatectomy. Patients then continue to receive leuprolide and bicalutamide with or without squalamine lactate for up to 6 additional weeks. After completion of study treatment, patients are followed periodically for at least 3 years. PROJECTED ACCRUAL: A total of 132 patients (66 per treatment arm) will be accrued for this study.

Official Title
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An Open Label Randomized Phase 2 Study To Evaluate The Activity, Tolerability, And Toxicity Of Combined Neoadjuvant Anti-angiogenesis and Androgen Ablation Therapy in Men Undergoing Radical Prostatectomy

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: bicalutamide
* Drug: leuprolide acetate
* Drug: squalamine lactate
* Procedure: adjuvant therapy
* Procedure: antiandrogen therapy
* Procedure: antiangiogenesis therapy
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy
* Procedure: releasing hormone agonist therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate Locally advanced disease No metastatic disease High-risk characteristics, meeting ≥ 1 of the following criteria: Large, hard tumor on digital exam Aggressive-appearing cancer cells on biopsy Prostate-specific antigen > 10 ng/mL PATIENT CHARACTERISTICS: Performance status 0-1 Life expectancy Not specified Hematopoietic WBC > 1,500/mm^3 Platelet count > 100,000/mm^3 Hemoglobin > 11.0 g/dL Hepatic Bilirubin < 2 times upper limit of normal (ULN) SGOT and SGPT < 2 times ULN PT and PTT normal Renal Creatinine < 1.8 g/dL Cardiovascular No history of ventricular arrhythmia or dysfunction No congestive heart failure No symptomatic coronary artery disease No prior myocardial infarction No history of thromboembolic disease (e.g., deep vein thrombosis or stroke) within the past 12 months No other significant cardiovascular disease Pulmonary No pulmonary embolism within the past 12 months No exercise-limiting respiratory disease Other Fertile patients must use effective barrier method contraception No sexual intercourse for 6 weeks after surgery No uncontrolled diabetes No serious acute infection No other malignancy except nonmelanoma skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy No prior squalamine lactate Chemotherapy No prior chemotherapy for prostate cancer No concurrent anticancer chemotherapy Endocrine therapy No concurrent systemic corticosteroids Radiotherapy No prior radiotherapy for prostate cancer No concurrent radiotherapy Surgery No prior surgery for prostate cancer No other concurrent surgery Other At least 6 weeks since prior and no concurrent use of over-the-counter or herbal drugs that have estrogenic activity No participation in another investigational study within the past 3 months No concurrent participation in another investigational study

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: bicalutamide|nan|
|Drug: leuprolide acetate|nan|
|Drug: squalamine lactate|nan|
|Procedure: adjuvant therapy|nan|
|Procedure: antiandrogen therapy|nan|
|Procedure: antiangiogenesis therapy|nan|
|Procedure: conventional surgery|nan|
|Procedure: neoadjuvant therapy|nan|
|Procedure: releasing hormone agonist therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response in terms of tumor volume as measured by transrectal ultrasound before and after neoadjuvant treatment |  |  | 
| Tumor response in terms of conventional histopathology as measured by prostatectomy specimens and Gleason scores in comparison to pre-treatment biopsies |  |  | 
| Tumor response in terms of molecular markers as measured by changes in VEGF, VEGF-flt-1, and integrin Alpha6Beta4, AlphaVBeta3, and AlphaVBeta5 expression in pre-treatment biopsy and post-treatment prostatectomy specimens |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety, feasibility, and tolerability as measured by CTCAE v3.0 |  |  | 
| Prostate-specific antigen (PSA) serology as measured by PSA value during and after completion of study treatment |  |  | 
| Survival for up to 3 years after completion of study treatment |  |  | 

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