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
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Prostate Cancer
- Sponsor
- OHSU Knight Cancer Institute
- Primary Endpoint
- Tumor response in terms of tumor volume as measured by transrectal ultrasound before and after neoadjuvant treatment
- Status
- Withdrawn
- Last Updated
- 13 years ago
Overview
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.
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
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 Outcomes
- Survival for up to 3 years after completion of study treatment
- 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