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

Sponsor

OHSU Knight Cancer Institute (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00244920

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	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	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2002

Actual Primary Completion Date :

Jun 1, 2007

Actual Study Completion Date :

Jun 1, 2007

Outcome Measures

Primary Outcome Measures

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

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

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