Study of Effectiveness of IMC-A12 Antibody Combined With Hormone Therapy Prior to Surgery to Treat Prostate Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Washington
ClinicalTrials.gov Identifier:
NCT00769795
First received: October 7, 2008
Last updated: May 8, 2013
Last verified: May 2013
  Purpose

The purpose of this study is to determine whether combination treatment of prostate cancer with IMC-A12 (an antibody which blocks insulin-like growth factor receptor activity) with hormonal therapy (testosterone lowering) before prostatectomy, will be more effective than prior results with hormonal therapy alone.


Condition Intervention Phase
Prostate Cancer
Drug: IMC-A12 in combination with androgen deprivation therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Neoadjuvant IMC-A12 Combined With Androgen Deprivation Prior to Prostatectomy

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 29
Study Start Date: October 2008
Study Completion Date: November 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Experimental Drug: IMC-A12 in combination with androgen deprivation therapy
All participants will begin bicalutamide 50 mg p.o. daily, one week prior to goserelin administration. On study day 1 the patients will be administered a single dose of goserelin 10.8 mg s.q. and continue on bicalutamide 50 mg daily for the duration of the trial. Total treatment length is 13 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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men 18 years or older with clinically localized prostate cancer who have chosen surgery (prostatectomy) and are at high risk of cancer relapse due to clinical stage, Gleason Score, PSA level, or a combination of the three.
  • Good health and laboratory values within reasonable limits

Exclusion Criteria:

  • Patients with prostate cancer that has spread outside the prostate.
  • Patients who have low testosterone
  • Patients who have received hormonal therapies or drugs which affect hormone metabolism
  • Patients with serious medical conditions such as diabetes, other cancers, stroke, cardiovascular disease.
  • Patients who are receiving other investigational therapy or chemotherapy.
  • Patients who are unwilling to use contraceptives during and for a short time after the study
  • Inability to give informed consent for any reason
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00769795

Locations
United States, Washington
University of Washington Medical Center
Seattle, Washington, United States, 98195
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Virginia Mason Medical Center
Seattle, Washington, United States, 98101
Sponsors and Collaborators
University of Washington
Investigators
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
  More Information

Additional Information:
No publications provided by University of Washington

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT00769795     History of Changes
Other Study ID Numbers: 6857, NIH P50 CA097186, 6857
Study First Received: October 7, 2008
Last Updated: May 8, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Washington:
prostate cancer
prostatic neoplasm
androgen deprivation therapy
insulin-like growth factor receptor I
neoadjuvant
prostatectomy

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014