Clinical trial NCT00769795: Study of Effectiveness of IMC-A12 Antibody Combined With Hormone Therapy Prior to Surgery to Treat Prostate Cancer
Official title: Phase II Study of Neoadjuvant IMC-A12 Combined With Androgen Deprivation Prior to Prostatectomy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: prostate cancer
prostatic neoplasm
androgen deprivation therapy
insulin-like growth factor receptor I
neoadjuvant
prostatectomy
Lead sponsor: University of Washington
Sponsor class: OTHER
First posted: 2008-10-09
Enrollment: 29
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: 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).
timeFrame: At the time of prostatectomy after 3 months of treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: University of Washington and Seattle Cancer Care Alliance
name: Bruce Montgomery, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Washington and Seattle Cancer Care Alliance
name: James P Dean, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Washington
name: Stephen Plymate, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Virginia Mason Medical Center
name: John M Corman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dean JP, Sprenger CC, Wan J, Haugk K, Ellis WJ, Lin DW, Corman JM, Dalkin BL, Mostaghel E, Nelson PS, Cohen P, Montgomery B, Plymate SR. Response of the insulin-like growth factor (IGF) system to IGF-IR inhibition and androgen deprivation in a neoadjuvant prostate cancer trial: effects of obesity and androgen deprivation. J Clin Endocrinol Metab. 2013 May;98(5):E820-8. doi: 10.1210/jc.2012-3856. Epub 2013 Mar 26.