Bicalutamide and Goserelin or Leuprolide Acetate With or Without Cixutumumab in Treating Patients With Newly Diagnosed Metastatic Prostate Cancer

A Randomized Phase II Study of Androgen Deprivation Combined With IMC-A12 Versus Androgen Deprivation Alone for Patients With New Hormone Sensitive Metastatic Prostate Cancer

This randomized phase II trial is studying bicalutamide, goserelin, or leuprolide acetate to see how well they work when given with or without cixutumumab in treating patients with newly diagnosed metastatic prostate cancer. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide, goserelin, or leuprolide acetate, may lessen the amount of androgens made by the body. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether bicalutamide, goserelin, or leuprolide acetate are more effective when given with or without cixutumumab in treating prostate cancer.

Study Overview

• Status: Completed
• Conditions: Prostate Adenocarcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Cixutumumab; Drug: Bicalutamide; Drug: Goserelin Acetate; Drug: Leuprolide Acetate

Detailed Description

PRIMARY OBJECTIVES:

I. To compare the undetectable prostate-specific antigen (PSA) rate (PSA < 0.2 ng/mL) after seven cycles (28 weeks) of protocol treatment between those randomized to a luteinizing hormone-releasing hormone (LHRH) agonist and bicalutamide and those randomized to a LHRH agonist, bicalutamide and IMC-A12 (cixutumumab).

SECONDARY OBJECTIVES:

I. To assess the safety and tolerability of the combination of IMC-A12 with a LHRH agonist and bicalutamide.

II. To compare the proportion of men who do not achieve a PSA of < 4 ng/mL between the two groups.

III. To assess the accuracy of the prognostic model of undetectable PSA that was developed from Southwest Oncology Group (SWOG)-9346 using current trial data from each arm.

IV. To assess serum samples and peripheral blood mononuclear cells (PBMNC) for pharmacodynamic activity with potential biomarkers for IMC-A12 (including, but not limited to: insulin-like growth factor [IGF]-I, free IGF-I, IGF-II, IGF binding protein [IGFBP]2, IGFBP3, growth hormone, insulin and C-peptide) obtained from optional blood specimens both before initiation of androgen deprivation therapy and twelve weeks after initiation of combined therapy.

V. To determine baseline pre-treatment circulating tumor cell (CTC) quantities and response to therapy (for those patients with detectable CTC levels >= 1) twelve weeks later.

VI. In the same subset of patients where CTC levels are obtained, determine baseline serum levels of micro-ribonucleic acids (RNAs) to include but not limited to microRNA (mi)-141 both before initiation of androgen deprivation therapy and twelve weeks after combined therapy.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive androgen deprivation therapy comprising bicalutamide orally (PO) once daily (QD) on days 1-28 and either goserelin acetate subcutaneously (SC) or leuprolide acetate intramuscularly (IM) every 1, 3, 4, 6, or 12 months. Patients also receive cixutumumab intravenously (IV) over 1 hour on days 1 and 15. Treatment repeats every 28 days for 7 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive androgen deprivation therapy comprising bicalutamide and either goserelin acetate or leuprolide acetate as in arm I.

After completion of study treatment, patients are followed up every 6 months for 2 years and then annually for 3 years.

• Study Type: Interventional
• Enrollment (Actual): 211
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA-Vancouver Cancer Centre
• United States
  • Alaska
    • Fairbanks, Alaska, United States, 99701
      • Fairbanks Memorial Hospital
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
    • Rogers, Arkansas, United States, 72758
      • Highlands Oncology Group-Rogers
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Marysville, California, United States, 95901
      • Fremont - Rideout Cancer Center
    • Pleasanton, California, United States, 94588
      • Valley Medical Oncology Consultants
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
    • Truckee, California, United States, 96161
      • Tahoe Forest Cancer Center
  • Colorado
    • Alamosa, Colorado, United States, 81101
      • San Luis Valley Regional Medical Center
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center - Anschutz Cancer Pavilion
    • Edwards, Colorado, United States, 81632
      • The Shaw Regional Cancer Center
    • Fort Collins, Colorado, United States, 80524
      • Poudre Valley Hospital
    • Fort Collins, Colorado, United States, 80528
      • Front Range Cancer Specialists
    • Glenwood Springs, Colorado, United States, 81601
      • Valley View Hospital Cancer Center
    • Grand Junction, Colorado, United States, 81502
      • Saint Mary's Hospital and Regional Medical Center
    • Montrose, Colorado, United States, 81401
      • Montrose Memorial Hospital
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • Smilow Cancer Hospital Care Center at Saint Francis
  • Florida
    • Orlando, Florida, United States, 32806
      • UF Cancer Center at Orlando Health
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Hawaii
    • 'Aiea, Hawaii, United States, 96701
      • Pali Momi Medical Center
    • 'Aiea, Hawaii, United States, 96701
      • Oncare Hawaii Inc-Pali Momi
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
    • Honolulu, Hawaii, United States, 96813
      • Straub Clinic and Hospital
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii Cancer Center
    • Honolulu, Hawaii, United States, 96817
      • Kuakini Medical Center
    • Honolulu, Hawaii, United States, 96826
      • Kapiolani Medical Center for Women and Children
    • Honolulu, Hawaii, United States, 96859
      • Tripler Army Medical Center
    • Honolulu, Hawaii, United States, 96813
      • Oncare Hawaii Inc-POB II
    • Honolulu, Hawaii, United States, 96817
      • OnCare Hawaii-Kuakini
    • Kailua, Hawaii, United States, 96734
      • Castle Medical Center
    • Lihue, Hawaii, United States, 96766
      • Wilcox Memorial Hospital and Kauai Medical Clinic
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
    • Lewiston, Idaho, United States, 83501
      • Saint Joseph Regional Medical Center
  • Illinois
    • Alton, Illinois, United States, 62002
      • Saint Anthony's Health
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Heartland Cancer Research NCORP
    • Hines, Illinois, United States, 60141
      • Hines Veterans Administration Hospital
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Springfield, Illinois, United States, 62781
      • Memorial Medical Center
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • Franciscan Saint Francis Health-Beech Grove
    • Richmond, Indiana, United States, 47374
      • Reid Health
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas - El Dorado
    • Fort Scott, Kansas, United States, 66701
      • Cancer Center of Kansas - Fort Scott
    • Independence, Kansas, United States, 67301
      • Cancer Center of Kansas-Independence
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas-Kingman
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Liberal, Kansas, United States, 67905
      • Cancer Center of Kansas-Liberal
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas - Newton
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas - Parsons
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas - Pratt
    • Salina, Kansas, United States, 67401
      • Cancer Center of Kansas - Salina
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas - Wellington
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas-Wichita Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Wichita
    • Wichita, Kansas, United States, 67208
      • Associates In Womens Health
    • Wichita, Kansas, United States, 67214
      • Wichita NCI Community Oncology Research Program
    • Wichita, Kansas, United States, 67214
      • Via Christi Regional Medical Center
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas - Winfield
  • Louisiana
    • Monroe, Louisiana, United States, 71202
      • University Health-Conway
    • Shreveport, Louisiana, United States, 71103
      • Louisiana State University Health Sciences Center Shreveport
    • Shreveport, Louisiana, United States, 71105
      • Highland Clinic
  • Michigan
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Hospital
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
    • Ann Arbor, Michigan, United States, 48106
      • Michigan Cancer Research Consortium NCORP
    • Battle Creek, Michigan, United States, 49017
      • Bronson Battle Creek
    • Big Rapids, Michigan, United States, 49307
      • Spectrum Health Big Rapids Hospital
    • Dearborn, Michigan, United States, 48124
      • Beaumont Hospital-Dearborn
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48236
      • Saint John Hospital and Medical Center
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • Flint, Michigan, United States, 48502
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Grand Rapids, Michigan, United States, 49503
      • Mercy Health Saint Mary's
    • Grand Rapids, Michigan, United States, 49503
      • Cancer Research Consortium of West Michigan NCORP
    • Jackson, Michigan, United States, 49201
      • Allegiance Health
    • Lansing, Michigan, United States, 48912
      • Sparrow Hospital
    • Livonia, Michigan, United States, 48154
      • Saint Mary Mercy Hospital
    • Muskegon, Michigan, United States, 49444
      • Mercy Health Mercy Campus
    • Pontiac, Michigan, United States, 48341
      • Saint Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • Saint Joseph Mercy Port Huron
    • Reed City, Michigan, United States, 49677
      • Spectrum Health Reed City Hospital
    • Saginaw, Michigan, United States, 48601
      • Saint Mary's of Michigan
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Warren, Michigan, United States, 48093
      • Saint John Macomb-Oakland Hospital
    • Wyoming, Michigan, United States, 49519
      • Metro Health Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Kansas City Veterans Affairs Medical Center
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
    • Billings, Montana, United States, 59101
      • Saint Vincent Healthcare
    • Billings, Montana, United States, 59102
      • Frontier Cancer Center and Blood Institute-Billings
    • Billings, Montana, United States, 59101
      • Montana Cancer Consortium NCORP
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Cancer Center
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Great Falls, Montana, United States, 59405
      • Benefis Healthcare- Sletten Cancer Institute
    • Helena, Montana, United States, 59601
      • Saint Peter's Community Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology PLLC
    • Missoula, Montana, United States, 59802
      • Saint Patrick Hospital - Community Hospital
    • Missoula, Montana, United States, 59802
      • Montana Cancer Specialists
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
    • Las Vegas, Nevada, United States, 89106
      • Nevada Cancer Research Foundation CCOP
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital
    • Hendersonville, North Carolina, United States, 28791
      • Margaret R Pardee Memorial Hospital
    • Statesville, North Carolina, United States, 28677
      • Iredell Memorial Hospital
    • Winston-Salem, North Carolina, United States, 27104
      • Southeast Clinical Oncology Research (SCOR) Consortium NCORP
  • Ohio
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital - Dayton
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Health Center
    • Dayton, Ohio, United States, 45420
      • Dayton NCI Community Oncology Research Program
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Hospital
    • Franklin, Ohio, United States, 45005-1066
      • Atrium Medical Center-Middletown Regional Hospital
    • Greenville, Ohio, United States, 45331
      • Wayne Hospital
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Troy, Ohio, United States, 45373
      • Upper Valley Medical Center
    • Wilmington, Ohio, United States, 45177
      • Clinton Memorial Hospital
    • Wright-Patterson Air Force Base, Ohio, United States, 45433-5529
      • Wright-Patterson Medical Center
    • Xenia, Ohio, United States, 45385
      • Greene Memorial Hospital
  • Oregon
    • Bend, Oregon, United States, 97701
      • Saint Charles Medical Center-Bend
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health Cancer Center
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Center
  • Texas
    • Fort Sam Houston, Texas, United States, 78234
      • Brooke Army Medical Center
    • Galveston, Texas, United States, 77555-0565
      • University of Texas Medical Branch
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Regional Medical Center
  • Washington
    • Anacortes, Washington, United States, 98221
      • Cancer Care Center at Island Hospital
    • Bellingham, Washington, United States, 98225
      • PeaceHealth Saint Joseph Medical Center
    • Bremerton, Washington, United States, 98310
      • Harrison HealthPartners Hematology and Oncology-Bremerton
    • Burien, Washington, United States, 98166
      • Highline Medical Center-Main Campus
    • Centralia, Washington, United States, 98531
      • Providence Regional Cancer System-Centralia
    • Everett, Washington, United States, 98201
      • Providence Regional Cancer Partnership
    • Federal Way, Washington, United States, 98003
      • Saint Francis Hospital
    • Issaquah, Washington, United States, 98029
      • Swedish Cancer Institute-Issaquah
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology
    • Kirkland, Washington, United States, 98033
      • EvergreenHealth Medical Center
    • Lakewood, Washington, United States, 98499
      • Saint Clare Hospital
    • Mount Vernon, Washington, United States, 98274
      • Skagit Valley Hospital
    • Olympia, Washington, United States, 98506-5166
      • Providence - Saint Peter Hospital
    • Poulsbo, Washington, United States, 98370
      • Harrison HealthPartners Hematology and Oncology-Poulsbo
    • Puyallup, Washington, United States, 98372
      • MultiCare Good Samaritan Hospital
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98104
      • Minor and James Medical PLLC
    • Seattle, Washington, United States, 98112
      • Group Health Cooperative-Seattle
    • Seattle, Washington, United States, 98122-4307
      • Swedish Medical Center-First Hill
    • Seattle, Washington, United States, 98122
      • The Polyclinic
    • Seattle, Washington, United States, 98104
      • Pacific Medical Center-First Hill
    • Seattle, Washington, United States, 98101
      • Virginia Mason CCOP
    • Seattle, Washington, United States, 98112
      • Group Health Cooperative of Puget Sound Oncology Consortium
    • Sedro-Woolley, Washington, United States, 98284
      • United General Hospital
    • Spokane, Washington, United States, 99218
      • Evergreen Hematology and Oncology PS
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Spokane, Washington, United States, 99220
      • Rockwood Clinic
    • Tacoma, Washington, United States, 98405
      • MultiCare Allenmore Hospital
    • Tacoma, Washington, United States, 98405
      • Northwest NCI Community Oncology Research Program
    • Tacoma, Washington, United States, 98405
      • Saint Joseph Medical Center
    • Tacoma, Washington, United States, 98415
      • MultiCare Health System
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospital and Clinics
  • Wyoming
    • Casper, Wyoming, United States, 82609
      • Rocky Mountain Oncology
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• All patients must have a histologically or cytologically proven diagnosis of adenocarcinoma of the prostate; note: If there is no formal biopsy report documenting the diagnosis of prostate cancer, the patient can be allowed on trial if the PSA level is at least 20, and there are at least three definitive metastatic lesions seen on scan; all patients must have had metastatic (M1) disease as evidenced by soft tissue and/or bony metastases prior to androgen deprivation therapy initiation; patients must have at least one of the following at the time they started androgen deprivation therapy:

  • Visceral disease (liver, lung, or other viscera)
  • Bone metastases to sites in either the axial (spine, pelvis, ribs, or skull) and/or the appendicular (clavicle, humerus, or femur) skeleton
  • Lymph node disease not considered to be encompassed within a single radiotherapy port (e.g., above the aortic bifurcation, etc.)
• Patients who have measurable disease must have radiographic assessment (at least an abdominal/pelvic computed tomography [CT]) within 28 days prior to registration; non-measurable disease must also be assessed (e.g., bone scan) in all patients within 56 days prior to registration; all disease must be assessed and documented on the Baseline Tumor Assessment Form
• Patients must have a PSA >= 5 ng/mL obtained within 90 days prior to initiation of androgen deprivation therapy
• Patients with known brain metastases are not eligible; brain imaging studies are not required for eligibility if the patient has no neurologic signs or symptoms, but if brain imaging studies are performed, they must be negative for disease
• Patient must have had no more than 30 days of prior medical castration for metastatic prostate cancer (prior androgen deprivation therapy is allowed if it was received with curative intent in the neoadjuvant, concurrent, and/or adjuvant fashion and at least 2 years have elapsed since completion of androgen deprivation therapy); the start date of medical castration is considered the day the patient first received an injection of a LHRH agonist, not an oral antiandrogen; if the method of castration is luteinizing hormone releasing hormone (LHRH) agonists (i.e., leuprolide or goserelin), the patient must be willing to continue the use of LHRH agonists and add bicalutamide for combined androgen deprivation therapy (ADT) during protocol treatment; the 30 day window begins from the date of receiving the LHRH agonist, not the oral antiandrogen; if the patient was on a different antiandrogen (e.g. flutamide), the patient must be willing to switch over to bicalutamide; patients must not have received bilateral orchiectomy; patients must not have received or be planning to receive LHRH antagonists (i.e., Degarelix); however, if the patient was initiated on a LHRH antagonist within the 30 day window and is willing to switch to a LHRH agonist with bicalutamide, he may enroll on the late induction group
• Patients who have not already started androgen deprivation therapy must be offered the opportunity to participate in the translational medicine studies; once a patient has started any form of antiandrogen (i.e., either bicalutamide or LHRH agonist), he is not eligible for any translational medicine studies
• Patients must not have received any prior cytotoxic chemotherapy for metastatic prostate cancer; prior cytotoxic chemotherapy with curative intent in the neoadjuvant or adjuvant setting is allowed; patients must not have received any prior treatment with agents that directly inhibit IGF or IGFRs
• Patients must not have received prior strontium-89, rhenium-186, rhenium-188, or samarium-153 radionuclide therapy within 28 days prior to registration
• Patients may have received prior radiation therapy or biologic therapy (e.g. vaccines, immunotherapy, anti-sense, small molecules, monoclonal antibodies); however, at least 28 days must have elapsed since completion of therapy and patient must have recovered from all side effects
• Patients may have received prior surgery; for all major surgeries, at least 28 days must have elapsed since completion and patient must have recovered from all side effects
• Leukocytes >= 3,000 mcL
• Absolute neutrophil count (ANC) >= 1,500 mcL
• Hemoglobin >= 9 g/dL
• Platelets >= 100,000/mcL
• Bilirubin =< 1.5 times the institutional upper limit of normal (ULN) (unless documented Gilbert's disease)
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 times the institutional ULN, or =< 5 times the institutional ULN if liver metastases are present
• Creatinine =< 2.0 x the institutional ULN or calculated creatinine clearance >= 40 mL/min
• International normalized ratio (INR) =< 1.5
• Partial thromboplastin time (PTT) no more than 5 seconds above the institutional ULN
• Patients receiving prophylactic low dose coumadin or low molecular weight heparin are eligible as long as they meet these coagulation criteria; patients requiring full-dose (therapeutic) anticoagulation are eligible provided that they have been on a stable dose of anticoagulation and the coagulation parameters are stable within the therapeutic range (e.g., INR 2-3 for patients on therapeutic warfarin)
• Patients must have a hemoglobin A1c (HgA1c) =< 7% AND fasting glucose of < 160 mg/dL or below the institutional ULN within 14 days prior to registration; patients with diabetes mellitus who meet this criterion must be on a stable dietary or therapeutic regimen for this condition
• Patients must not have a history of symptomatic congestive heart failure or a known ejection fraction (left ventricular ejection fraction [LVEF]) that is >= 10% below the lower limit of normal (LLN); if left ventricular (LV) dysfunction is suspected, but not confirmed by review of past medical history, a multi gated acquisition scan (MUGA) or echocardiogram must be obtained within 90 days prior to registration
• Patient must not have a history of allergic reaction attributed to compounds of similar chemical or biologic composition to IMC-A12; patients must not have received prior chimerized or murine monoclonal antibody therapy
• Patients must have a Zubrod performance status of 0 - 2; Zubrod performance status 3 will be allowed if from bone pain only
• Patients with human immunodeficiency virus (HIV) positivity requiring antiretroviral therapy are not eligible for this study
• Patients must have no plans to receive concurrent chemotherapy, hormonal therapy (other than the LHRH agonist and oral anti-androgen), radiotherapy, immunotherapy or any other type of therapy for treatment of cancer while on this protocol treatment; concurrent bone targeting agents that do not have effect on PSA (i.e. denosumab or zoledronic acid) are allowed
• Patients must have no plans to receive concurrent five-alpha reductase inhibitors (e.g. finasteride and dutasteride), ketoconazole, diethylstilbestrol/DES, or other estrogen-based therapy while on this protocol treatment
• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years
• Men of reproductive potential must have agreed to use an effective contraceptive method while receiving treatment on this study and for at least three months after protocol treatment ends
• All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
• As part of the OPEN registration process, the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (androgen deprivation and cixutumumab); Patients receive androgen deprivation therapy comprising bicalutamide PO QD on days 1-28 and either goserelin acetate SC or leuprolide acetate IM every 1, 3, 4, 6, or 12 months. Patients also receive cixutumumab IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for 7 courses in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Biological: Cixutumumab; Given IV; Other Names: IMC-A12; Anti-IGF-1R Recombinant Monoclonal Antibody IMC-A12; Drug: Bicalutamide; Given PO; Other Names: Casodex; Cosudex; ICI 176,334; ICI 176334; Drug: Goserelin Acetate; Given SC; Other Names: ZDX; Zoladex; Drug: Leuprolide Acetate; Given IM; Other Names: Enantone; LEUP; Lupron; Lupron Depot; Leuprorelin Acetate; A-43818; Abbott 43818; Abbott-43818; Carcinil; Depo-Eligard; Eligard; Enanton; Enantone-Gyn; Ginecrin; Leuplin; Lucrin; Lucrin Depot; Lupron Depot-3 Month; Lupron Depot-4 Month; Lupron Depot-Ped; Procren; Procrin; Prostap; TAP-144; Trenantone; Uno-Enantone; Viadur
Active Comparator: Arm II (androgen deprivation therapy); Patients receive androgen deprivation therapy comprising bicalutamide and either goserelin acetate or leuprolide acetate as in arm I.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Drug: Bicalutamide; Given PO; Other Names: Casodex; Cosudex; ICI 176,334; ICI 176334; Drug: Goserelin Acetate; Given SC; Other Names: ZDX; Zoladex; Drug: Leuprolide Acetate; Given IM; Other Names: Enantone; LEUP; Lupron; Lupron Depot; Leuprorelin Acetate; A-43818; Abbott 43818; Abbott-43818; Carcinil; Depo-Eligard; Eligard; Enanton; Enantone-Gyn; Ginecrin; Leuplin; Lucrin; Lucrin Depot; Lupron Depot-3 Month; Lupron Depot-4 Month; Lupron Depot-Ped; Procren; Procrin; Prostap; TAP-144; Trenantone; Uno-Enantone; Viadur

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Undetectable PSA Rate	Undetectable PSA rate (<= 0.2 ng/mL) after seven cycles (28 weeks) of protocol treatment	7 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity	Only adverse events that are possibly, probably or definitely related to study drug are reported.	Up to 28 weeks
Proportion of Patients Who do Not Achieve a Partial PSA Response	A partial PSA response is considered <= 4 ng/mL	Up to 5 years
Accuracy of the Prognostic Model of Undetectable PSA (Developed From SWOG-9346)	The logistic regression algorithm for predicting undetectable PSA that was developed for SWOG-9346 using its baseline risk factors (age at registration, performance status, baseline PSA, and bone pain) will be applied to each arm of this trial to evaluate the level of agreement between the observed and predicted undetectable PSA rates.	Up to 5 years
Correlation of microRNA Measures With 28-week PSA Response	The Friedman test will be used to evaluate correlations between microRNA measures (CT) and 28-week PSA response.	Baseline to 28 weeks
Correlation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) Counts	The Friedman test will be used to evaluate correlations between microRNA measures (CT) and Baseline CTCs.	Baseline
Change in Level of CTCs	Will be correlated with 28-week PSA response.	Baseline to 28 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Level of IGF-I, Free IGF-I and C-peptide	Serum samples and peripheral blood mononuclear cells (PBMNC) for pharmacodynamic activity with potential biomarkers for IMC-A12 (including, but not limited to: IGF-I, free IGF-I and C-peptide) obtained from optional blood specimens both before initiation of androgen deprivation therapy and twelve weeks after initiation of combined therapy. Results are reported as the difference between baseline and 12 weeks after start of therapy.	Baseline to 12 weeks
Change in Level of IGFBP2, IGFBP3 and Growth Hormone	Serum samples and peripheral blood mononuclear cells (PBMNC) for pharmacodynamic activity with potential biomarkers for IMC-A12 (including, but not limited to: IGFBP2, IGFBP3 and Growth Hormone) obtained from optional blood specimens both before initiation of androgen deprivation therapy and twelve weeks after initiation of combined therapy. Results are reported as the difference between baseline and 12 weeks after start of therapy.	Baseline to 12 weeks
Change in Level of Insulin	Serum samples and peripheral blood mononuclear cells (PBMNC) for pharmacodynamic activity with potential biomarkers for IMC-A12 (insulin) obtained from optional blood specimens both before initiation of androgen deprivation therapy and twelve weeks after initiation of combined therapy. Results are reported as the difference between baseline and 12 weeks after start of therapy.	Baseline to 12 weeks

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Evan Yu, Southwest Oncology Group

Publications and helpful links

General Publications

• Yu EY, Li H, Higano CS, Agarwal N, Pal SK, Alva A, Heath EI, Lam ET, Gupta S, Lilly MB, Inoue Y, Chi KN, Vogelzang NJ, Quinn DI, Cheng HH, Plymate SR, Hussain M, Tangen CM, Thompson IM Jr. SWOG S0925: A Randomized Phase II Study of Androgen Deprivation Combined With Cixutumumab Versus Androgen Deprivation Alone in Patients With New Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol. 2015 May 10;33(14):1601-8. doi: 10.1200/JCO.2014.59.4127. Epub 2015 Apr 6.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): August 23, 2017

Study Registration Dates

• First Submitted: May 7, 2010
• First Submitted That Met QC Criteria: May 7, 2010
• First Posted (Estimate): May 10, 2010

Study Record Updates

• Last Update Posted (Actual): February 26, 2018
• Last Update Submitted That Met QC Criteria: February 23, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Androgen Antagonists; Leuprolide; Goserelin; Antibodies, Monoclonal; Bicalutamide
• Other Study ID Numbers: NCI-2011-02003 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA032102 (U.S. NIH Grant/Contract); SWOG-S0925; CDR0000663832; S0925 (Other Identifier: CTEP)