Study of Effectiveness of IMC-A12 Antibody Combined With Hormone Therapy Prior to Surgery to Treat Prostate Cancer
|Prostate Cancer||Drug: IMC-A12 Drug: Bicalutamide Drug: Goserelin||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase II Study of Neoadjuvant IMC-A12 Combined With Androgen Deprivation Prior to Prostatectomy|
- The primary endpoint of the study is to determine the effects of combining androgen deprivation with IMC-A12 on pathologic tumor stage (pathologic complete response). [ Time Frame: At the time of prostatectomy after 3 months of treatment ]
|Study Start Date:||October 2008|
|Study Completion Date:||November 2011|
|Primary Completion Date:||August 2011 (Final data collection date for primary outcome measure)|
Bicalutamide 50 mg daily for 12 weeks Goserelin 10.8 mg SC once IMC-A12 10 mg/kg IV every three weeks for 12 weeks
IMC-A12 will be administered every 2 weeks for a total of 6 doses at 10 mg/kg per dose. The last dose of IMC-A12 will be at least 2 weeks prior to prostatectomy.
Other Name: CixutumumabDrug: Bicalutamide
Bicalutamide 50 mg daily orally for 12 weeksDrug: Goserelin
10.8 mg subcutaneous once
Androgen deprivation has long been the principal means of controlling advanced prostate cancer, but it does not cure the disease and all patients ultimately progress if tumor is not eliminated with definitive local therapy. Neoadjuvant androgen deprivation prior to radical prostatectomy can downstage localized disease and reduce the likelihood of residual disease at the margins, but does not improve failure free survival. It has been demonstrated that despite androgen deprivation with luteinizing hormone releasing hormone (LHRH) agonists or orchiectomy, prostate tissue and prostate cancer maintain levels of androgens which are more than adequate to continue to stimulate the androgen receptor and downstream signaling. These levels of androgen may continue to allow both survival of tumor cells and induction of resistance by overexpression of receptor.
The anti-insulin-like growth factor type I receptor (IGF-IR) antibody IMC-A12 blocks translocation of the androgen receptor to the nucleus, dramatically augmenting efficacy of androgen deprivation in human prostate xenograft models. The combination of androgen deprivation with IMC-A12 is anticipated to more effectively treat cancer within the prostate, optimizing local control, while potentially eliminating micrometastatic disease. We propose to test this hypothesis in this phase II study, administering neoadjuvant androgen deprivation therapy IMC-A12 prior to radical prostatectomy for patients with clinically localized, high risk prostate cancer for 3 months.
Patients with clinically localized, and surgically resectable (cT1-T3) prostate cancer, at high risk for relapse who are candidates for radical prostatectomy will be treated with LHRH agonist and androgen receptor antagonist combined with IMC-A12, 10 mg/kg given intravenously every 14 days for 12 weeks. Patients will undergo biopsy of the prostate prior to treatment and radical prostatectomy 12 weeks after initiation of treatment.
The primary endpoint of the study is to evaluate the ability of LHRH agonist with IMC-A12 to induce a complete pathologic remission
Samples from the current study will be compared to control, untreated prostatectomy specimens from the Northwest Prostate SPORE Tissue Core and a concurrent set of specimens from patients treated with 12 weeks of combined androgen deprivation.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00769795
|United States, Washington|
|Virginia Mason Medical Center|
|Seattle, Washington, United States, 98101|
|Seattle Cancer Care Alliance|
|Seattle, Washington, United States, 98109|
|University of Washington Medical Center|
|Seattle, Washington, United States, 98195|
|Principal Investigator:||Bruce Montgomery, M.D.||University of Washington and Seattle Cancer Care Alliance|
|Principal Investigator:||James P Dean, M.D., Ph.D.||University of Washington and Seattle Cancer Care Alliance|
|Principal Investigator:||Stephen Plymate, M.D.||University of Washington|
|Principal Investigator:||John M Corman, MD||Virginia Mason Medical Center|