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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01120236
• Collaborator: (none)
• Enrollment: 211
• Locations: 170
• Arms: 2
• Duration (Months): 80.7
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Adenocarcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer	Drug: Bicalutamide; Biological: Cixutumumab; Drug: Goserelin Acetate; Other: Laboratory Biomarker Analysis; Drug: Leuprolide Acetate; Other: Pharmacological Study	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

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

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

3. 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.

4. 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.

5. 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.

6. 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 Design

• Study Type: Interventional
• Actual Enrollment: 211 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Dec 1, 2010
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Aug 23, 2017

Arms and Interventions

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.	Drug: Bicalutamide; Given PO; Other Names: Casodex Cosudex ICI 176,334 ICI 176334 ; Biological: Cixutumumab; Given IV; Other Names: Anti-IGF-1R Recombinant Monoclonal Antibody IMC-A12 IMC-A12 ; Drug: Goserelin Acetate; Given SC; Other Names: ZDX Zoladex ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Leuprolide Acetate; Given IM; Other Names: A-43818 Abbott 43818 Abbott-43818 Carcinil Depo-Eligard Eligard Enanton Enantone Enantone-Gyn Ginecrin LEUP Leuplin Leuprorelin Acetate Lucrin Lucrin Depot Lupron Lupron Depot Lupron Depot-3 Month Lupron Depot-4 Month Lupron Depot-Ped Procren Procrin Prostap TAP-144 Trenantone Uno-Enantone Viadur ; Other: Pharmacological Study; Correlative studies
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.	Drug: Bicalutamide; Given PO; Other Names: Casodex Cosudex ICI 176,334 ICI 176334 ; Drug: Goserelin Acetate; Given SC; Other Names: ZDX Zoladex ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Leuprolide Acetate; Given IM; Other Names: A-43818 Abbott 43818 Abbott-43818 Carcinil Depo-Eligard Eligard Enanton Enantone Enantone-Gyn Ginecrin LEUP Leuplin Leuprorelin Acetate Lucrin Lucrin Depot Lupron Lupron Depot Lupron Depot-3 Month Lupron Depot-4 Month Lupron Depot-Ped Procren Procrin Prostap TAP-144 Trenantone Uno-Enantone Viadur ; Other: Pharmacological Study; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Undetectable PSA Rate [7 months]

   Undetectable PSA rate (<= 0.2 ng/mL) after seven cycles (28 weeks) of protocol treatment

Secondary Outcome Measures

1. Toxicity [Up to 28 weeks]

   Only adverse events that are possibly, probably or definitely related to study drug are reported.

2. Proportion of Patients Who do Not Achieve a Partial PSA Response [Up to 5 years]

   A partial PSA response is considered <= 4 ng/mL

3. Accuracy of the Prognostic Model of Undetectable PSA (Developed From SWOG-9346) [Up to 5 years]

   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.

4. Correlation of microRNA Measures With 28-week PSA Response [Baseline to 28 weeks]

   The Friedman test will be used to evaluate correlations between microRNA measures (CT) and 28-week PSA response.

5. Correlation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) Counts [Baseline]

   The Friedman test will be used to evaluate correlations between microRNA measures (CT) and Baseline CTCs.

6. Change in Level of CTCs [Baseline to 28 weeks]

   Will be correlated with 28-week PSA response.

Other Outcome Measures

1. Change in Level of IGF-I, Free IGF-I and C-peptide [Baseline to 12 weeks]

   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.

2. Change in Level of IGFBP2, IGFBP3 and Growth Hormone [Baseline to 12 weeks]

   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.

3. Change in Level of Insulin [Baseline to 12 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fairbanks Memorial Hospital	Fairbanks	Alaska	United States	99701
2	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
3	Highlands Oncology Group-Rogers	Rogers	Arkansas	United States	72758
4	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
5	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
6	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
7	Fremont - Rideout Cancer Center	Marysville	California	United States	95901
8	Valley Medical Oncology Consultants	Pleasanton	California	United States	94588
9	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
10	Tahoe Forest Cancer Center	Truckee	California	United States	96161
11	San Luis Valley Regional Medical Center	Alamosa	Colorado	United States	81101
12	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado	United States	80045
13	The Shaw Regional Cancer Center	Edwards	Colorado	United States	81632
14	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
15	Front Range Cancer Specialists	Fort Collins	Colorado	United States	80528
16	Valley View Hospital Cancer Center	Glenwood Springs	Colorado	United States	81601
17	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado	United States	81502
18	Montrose Memorial Hospital	Montrose	Colorado	United States	81401
19	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut	United States	06105
20	UF Cancer Center at Orlando Health	Orlando	Florida	United States	32806
21	Moffitt Cancer Center	Tampa	Florida	United States	33612
22	Oncare Hawaii Inc-Pali Momi	'Aiea	Hawaii	United States	96701
23	Pali Momi Medical Center	'Aiea	Hawaii	United States	96701
24	Oncare Hawaii Inc-POB II	Honolulu	Hawaii	United States	96813
25	Queen's Medical Center	Honolulu	Hawaii	United States	96813
26	Straub Clinic and Hospital	Honolulu	Hawaii	United States	96813
27	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
28	Kuakini Medical Center	Honolulu	Hawaii	United States	96817
29	OnCare Hawaii-Kuakini	Honolulu	Hawaii	United States	96817
30	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
31	Tripler Army Medical Center	Honolulu	Hawaii	United States	96859
32	Castle Medical Center	Kailua	Hawaii	United States	96734
33	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii	United States	96766
34	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
35	Saint Joseph Regional Medical Center	Lewiston	Idaho	United States	83501
36	Saint Anthony's Health	Alton	Illinois	United States	62002
37	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
38	Heartland Cancer Research NCORP	Decatur	Illinois	United States	62526
39	Hines Veterans Administration Hospital	Hines	Illinois	United States	60141
40	Loyola University Medical Center	Maywood	Illinois	United States	60153
41	Memorial Medical Center	Springfield	Illinois	United States	62781
42	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana	United States	46107
43	Reid Health	Richmond	Indiana	United States	47374
44	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
45	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
46	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
47	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
48	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
49	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
50	Cancer Center of Kansas-Kingman	Kingman	Kansas	United States	67068
51	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
52	Cancer Center of Kansas-Liberal	Liberal	Kansas	United States	67905
53	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
54	Cancer Center of Kansas - Parsons	Parsons	Kansas	United States	67357
55	Cancer Center of Kansas - Pratt	Pratt	Kansas	United States	67124
56	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
57	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
58	Associates In Womens Health	Wichita	Kansas	United States	67208
59	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
60	Cancer Center of Kansas - Wichita	Wichita	Kansas	United States	67214
61	Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
62	Wichita NCI Community Oncology Research Program	Wichita	Kansas	United States	67214
63	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
64	University Health-Conway	Monroe	Louisiana	United States	71202
65	Louisiana State University Health Sciences Center Shreveport	Shreveport	Louisiana	United States	71103
66	Highland Clinic	Shreveport	Louisiana	United States	71105
67	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106-0995
68	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan	United States	48106
69	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
70	Bronson Battle Creek	Battle Creek	Michigan	United States	49017
71	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan	United States	49307
72	Beaumont Hospital-Dearborn	Dearborn	Michigan	United States	48124
73	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
74	Henry Ford Hospital	Detroit	Michigan	United States	48202
75	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
76	Hurley Medical Center	Flint	Michigan	United States	48502
77	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
78	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan	United States	49503
79	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
80	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
81	Allegiance Health	Jackson	Michigan	United States	49201
82	Sparrow Hospital	Lansing	Michigan	United States	48912
83	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
84	Mercy Health Mercy Campus	Muskegon	Michigan	United States	49444
85	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
86	Saint Joseph Mercy Port Huron	Port Huron	Michigan	United States	48060
87	Spectrum Health Reed City Hospital	Reed City	Michigan	United States	49677
88	Saint Mary's of Michigan	Saginaw	Michigan	United States	48601
89	Munson Medical Center	Traverse City	Michigan	United States	49684
90	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
91	Metro Health Hospital	Wyoming	Michigan	United States	49519
92	Kansas City Veterans Affairs Medical Center	Kansas City	Missouri	United States	64128
93	Billings Clinic Cancer Center	Billings	Montana	United States	59101
94	Montana Cancer Consortium NCORP	Billings	Montana	United States	59101
95	Saint Vincent Healthcare	Billings	Montana	United States	59101
96	Frontier Cancer Center and Blood Institute-Billings	Billings	Montana	United States	59102
97	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
98	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
99	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
100	Great Falls Clinic	Great Falls	Montana	United States	59405
101	Saint Peter's Community Hospital	Helena	Montana	United States	59601
102	Glacier Oncology PLLC	Kalispell	Montana	United States	59901
103	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
104	Montana Cancer Specialists	Missoula	Montana	United States	59802
105	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
106	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
107	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada	United States	89106
108	University of Rochester	Rochester	New York	United States	14642
109	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
110	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina	United States	28791
111	Iredell Memorial Hospital	Statesville	North Carolina	United States	28677
112	Southeast Clinical Oncology Research (SCOR) Consortium NCORP	Winston-Salem	North Carolina	United States	27104
113	Grandview Hospital	Dayton	Ohio	United States	45405
114	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
115	Miami Valley Hospital	Dayton	Ohio	United States	45409
116	Samaritan North Health Center	Dayton	Ohio	United States	45415
117	Dayton NCI Community Oncology Research Program	Dayton	Ohio	United States	45420
118	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
119	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
120	Wayne Hospital	Greenville	Ohio	United States	45331
121	Kettering Medical Center	Kettering	Ohio	United States	45429
122	Upper Valley Medical Center	Troy	Ohio	United States	45373
123	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
124	Wright-Patterson Medical Center	Wright-Patterson Air Force Base	Ohio	United States	45433-5529
125	Greene Memorial Hospital	Xenia	Ohio	United States	45385
126	Saint Charles Medical Center-Bend	Bend	Oregon	United States	97701
127	AnMed Health Cancer Center	Anderson	South Carolina	United States	29621
128	Medical University of South Carolina	Charleston	South Carolina	United States	29425
129	Spartanburg Medical Center	Spartanburg	South Carolina	United States	29303
130	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234
131	University of Texas Medical Branch	Galveston	Texas	United States	77555-0565
132	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
133	Danville Regional Medical Center	Danville	Virginia	United States	24541
134	Cancer Care Center at Island Hospital	Anacortes	Washington	United States	98221
135	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	United States	98225
136	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington	United States	98310
137	Highline Medical Center-Main Campus	Burien	Washington	United States	98166
138	Providence Regional Cancer System-Centralia	Centralia	Washington	United States	98531
139	Providence Regional Cancer Partnership	Everett	Washington	United States	98201
140	Saint Francis Hospital	Federal Way	Washington	United States	98003
141	Swedish Cancer Institute-Issaquah	Issaquah	Washington	United States	98029
142	Kadlec Clinic Hematology and Oncology	Kennewick	Washington	United States	99336
143	EvergreenHealth Medical Center	Kirkland	Washington	United States	98033
144	Saint Clare Hospital	Lakewood	Washington	United States	98499
145	Skagit Valley Hospital	Mount Vernon	Washington	United States	98274
146	Providence - Saint Peter Hospital	Olympia	Washington	United States	98506-5166
147	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington	United States	98370
148	MultiCare Good Samaritan Hospital	Puyallup	Washington	United States	98372
149	Virginia Mason CCOP	Seattle	Washington	United States	98101
150	Harborview Medical Center	Seattle	Washington	United States	98104
151	Minor and James Medical PLLC	Seattle	Washington	United States	98104
152	Pacific Medical Center-First Hill	Seattle	Washington	United States	98104
153	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
154	Group Health Cooperative of Puget Sound Oncology Consortium	Seattle	Washington	United States	98112
155	Group Health Cooperative-Seattle	Seattle	Washington	United States	98112
156	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
157	The Polyclinic	Seattle	Washington	United States	98122
158	University of Washington Medical Center	Seattle	Washington	United States	98195
159	United General Hospital	Sedro-Woolley	Washington	United States	98284
160	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
161	Evergreen Hematology and Oncology PS	Spokane	Washington	United States	99218
162	Rockwood Clinic	Spokane	Washington	United States	99220
163	MultiCare Allenmore Hospital	Tacoma	Washington	United States	98405
164	Northwest NCI Community Oncology Research Program	Tacoma	Washington	United States	98405
165	Saint Joseph Medical Center	Tacoma	Washington	United States	98405
166	Multicare Health System	Tacoma	Washington	United States	98415
167	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington	United States	98801
168	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
169	Welch Cancer Center	Sheridan	Wyoming	United States	82801
170	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Evan Yu, Southwest Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01120236
• Other Study ID Numbers: NCI-2011-02003; NCI-2011-02003; SWOG-S0925; CDR0000663832; S0925; S0925; U10CA032102
• First Posted: May 10, 2010
• Last Update Posted: Feb 26, 2018
• Last Verified: Feb 1, 2018

• Additional relevant MeSH terms: Prostatic Neoplasms; Leuprolide; Goserelin; Bicalutamide; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	Arm I (Androgen Deprivation and Cixutumumab)	Arm II (Androgen Deprivation Therapy)
Arm/Group Description	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. Bicalutamide: Given PO Cixutumumab: Given IV Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Pharmacological Study: Correlative studies	Patients receive androgen deprivation therapy comprising bicalutamide and either goserelin acetate or leuprolide acetate as in arm I. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Pharmacological Study: Correlative studies
Period Title: Overall Study
STARTED	105	106
Ineligble	0	1
COMPLETED	105	105
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Arm I (Androgen Deprivation and Cixutumumab)	Arm II (Androgen Deprivation Therapy)	Total
Arm/Group Description	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. Bicalutamide: Given PO Cixutumumab: Given IV Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Pharmacological Study: Correlative studies	Patients receive androgen deprivation therapy comprising bicalutamide and either goserelin acetate or leuprolide acetate as in arm I. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Pharmacological Study: Correlative studies	Total of all reporting groups
Overall Participants	105	105	210
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	65	66	66
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	105 100%	105 100%	210 100%
Race/Ethnicity, Customized (participants) [Number]
Black	4 3.8%	10 9.5%	14 6.7%
White	94 89.5%	88 83.8%	182 86.7%
Other	7 6.7%	7 6.7%	14 6.7%
Region of Enrollment (participants) [Number]
United States	105 100%	105 100%	210 100%
Prostate-Specific Antigen (PSA) (ng/mL) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [ng/mL]	31	37	34
Weight (kg) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kg]	90	86	88
Body Mass Index (BMI) (participants) [Number]
<18.5 (underweight)	1 1%	2 1.9%	3 1.4%
18.5 to 24.9 (normal weight)	21 20%	29 27.6%	50 23.8%
25 to 29.9 (overweight)	36 34.3%	39 37.1%	75 35.7%
>= 30 (obese)	43 41%	33 31.4%	76 36.2%
Unknown	4 3.8%	2 1.9%	6 2.9%
Gleason Score (participants) [Number]
<7	8 7.6%	6 5.7%	14 6.7%
7	29 27.6%	11 10.5%	40 19%
>=7	63 60%	82 78.1%	145 69%
Unknown	5 4.8%	6 5.7%	11 5.2%
Zubrod Performance Score (participants) [Number]
0	62 59%	65 61.9%	127 60.5%
1	41 39%	38 36.2%	79 37.6%
2	2 1.9%	2 1.9%	4 1.9%
Site of Metastasis (participants) [Number]
Lymph Node Only	15 14.3%	9 8.6%	24 11.4%
Bone Only	56 53.3%	63 60%	119 56.7%
Lymph Node and Bone	19 18.1%	17 16.2%	36 17.1%
Visceral	15 14.3%	16 15.2%	31 14.8%
Bone Pain (participants) [Number]
Number [participants]	28 26.7%	35 33.3%	63 30%
Early Induction Androgen Deprivation (participants) [Number]
Number [participants]	59 56.2%	65 61.9%	124 59%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

One patient from Arm II (androgen deprivation therapy) was ineligible because of lack of a demonstrable radiographic metastasis. This patient was excluded from analyses.

Arm/Group Title	Arm I (Androgen Deprivation and Cixutumumab)	Arm II (Androgen Deprivation Therapy)
Arm/Group Description	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. Bicalutamide: Given PO Cixutumumab: Given IV Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Pharmacological Study: Correlative studies	Patients receive androgen deprivation therapy comprising bicalutamide and either goserelin acetate or leuprolide acetate as in arm I. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Pharmacological Study: Correlative studies
Measure Participants	105	105
Number [participants]	42 40%	34 32.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Androgen Deprivation and Cixutumumab), Arm II (Androgen Deprivation Therapy)
	Comments	An intention-to-treat approach was used in analysis of the primary endpoint. A 45% undetectable PSA <= 0.2 ng/mL rate at 28 weeks was assumed for (control) arm II , based on data from SWOG 9346. Using a one-sided type I error rate of 0.10, we had 90% statistical power to detect an absolute difference of 20% in the undetectable PSA rate with the addition of cixutumumab using Fisher's exact test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.16
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.24
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Arm I (Androgen Deprivation and Cixutumumab) represents the numerator and Arm II (Androgen Deprivation Therapy) represents the denominator for relative risk.

2. Secondary Outcome

Title	Toxicity
Description	Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time Frame	Up to 28 weeks

Outcome Measure Data

Analysis Population Description

All participants receiving at least some protocol treatment were included in toxicity analysis. Four patients on Arm I (androgen deprivation and cixutumumab) and two patients on Arm II (androgen deprivation therapy) did not receive any protocol treatment and were therefore excluded from this analysis.

Arm/Group Title	Arm I (Androgen Deprivation and Cixutumumab)	Arm II (Androgen Deprivation Therapy)
Arm/Group Description	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. Bicalutamide: Given PO Cixutumumab: Given IV Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Pharmacological Study: Correlative studies	Patients receive androgen deprivation therapy comprising bicalutamide and either goserelin acetate or leuprolide acetate as in arm I. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Pharmacological Study: Correlative studies
Measure Participants	101	104
Alanine aminotransferase increased	1 1%	0 0%
Anemia	1 1%	1 1%
Anxiety	0 0%	1 1%
Aspartate aminotransferase increased	1 1%	0 0%
Cognitive disturbance	1 1%	0 0%
Depression	0 0%	1 1%
Erectile dysfunction	1 1%	0 0%
Exostosis	1 1%	0 0%
Glucose intolerance	0 0%	1 1%
Hot flashes	1 1%	1 1%
Hypercalcemia	2 1.9%	0 0%
Hyperglycemia	8 7.6%	0 0%
Hypertension	2 1.9%	2 1.9%
Hypertriglyceridemia	1 1%	0 0%
Left ventricular systolic dysfunction	1 1%	0 0%
Nausea	1 1%	0 0%
Obesity	1 1%	1 1%
Soft tissue infection	1 1%	0 0%
Urinary tract infection	1 1%	0 0%
Urinary tract obstruction	0 0%	1 1%
Vomiting	1 1%	0 0%

3. Secondary Outcome

Title	Proportion of Patients Who do Not Achieve a Partial PSA Response
Description	A partial PSA response is considered <= 4 ng/mL
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

One patient from Arm II (androgen deprivation therapy) was ineligible because of lack of a demonstrable radiographic metastasis. This patient was excluded from analyses.

Arm/Group Title	Arm I (Androgen Deprivation and Cixutumumab)	Arm II (Androgen Deprivation Therapy)
Arm/Group Description	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. Bicalutamide: Given PO Cixutumumab: Given IV Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Pharmacological Study: Correlative studies	Patients receive androgen deprivation therapy comprising bicalutamide and either goserelin acetate or leuprolide acetate as in arm I. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Pharmacological Study: Correlative studies
Measure Participants	105	105
Number [participants]	46 43.8%	56 53.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Androgen Deprivation and Cixutumumab), Arm II (Androgen Deprivation Therapy)
	Comments	Proportion of patients in each arm with PSA > 4 ng/mL after seven cycles of protocol treatment were compared.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.82
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Arm I (Androgen Deprivation and Cixutumumab) represents the numerator and Arm II (Androgen Deprivation Therapy) represents the denominator for relative risk.

4. Secondary Outcome

Title	Accuracy of the Prognostic Model of Undetectable PSA (Developed From SWOG-9346)
Description	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.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

The data from this trial was intended to be used as a validation dataset for the prognostic model built using data from SWOG-9346. However, data for this objective was not collected.

Arm/Group Title	Arm I (Androgen Deprivation and Cixutumumab)	Arm II (Androgen Deprivation Therapy)
Arm/Group Description	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. Bicalutamide: Given PO Cixutumumab: Given IV Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Pharmacological Study: Correlative studies	Patients receive androgen deprivation therapy comprising bicalutamide and either goserelin acetate or leuprolide acetate as in arm I. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Pharmacological Study: Correlative studies
Measure Participants	0	0

5. Secondary Outcome

Title	Correlation of microRNA Measures With 28-week PSA Response
Description	The Friedman test will be used to evaluate correlations between microRNA measures (CT) and 28-week PSA response.
Time Frame	Baseline to 28 weeks

Outcome Measure Data

Analysis Population Description

Among the 50 patients in this biomarker substudy, 10 patients were excluded: 1 ineligible for S0925, 6 started LHRH therapy prior to registration, 3 had insufficient miRNA samples. The remaining 40 patienets were included in this analysis.

Arm/Group Title	PSA Complete Response	PSA Partial Response	PSA Non-Responders
Arm/Group Description	Patients who had a PSA level of ≤ 0.2 ng/mL at 28 weeks after registration, pooled treatment Arm I (androgen deprivation and cixutumumab) & Arm II (androgen deprivation therapy)	Patients who had a PSA level of >0.2 ng/mL and <= 4.0 ng/mL at 28 weeks after registration, pooled treatment Arm I (androgen deprivation and cixutumumab) & Arm II (androgen deprivation therapy)	Patients who had a PSA level of > 4.0 ng/mL at 28 weeks after registration, pooled treatment Arm I (androgen deprivation and cixutumumab) & Arm II (androgen deprivation therapy)
Measure Participants	22	5	13
miR-141	32.6	32.0	31.5
miR-200a	34.5	33.8	33.8
miR-200b	33.6	33.6	32.6
miR-210	32.5	32.1	32.3
miR-375	33.0	32.6	29.5

6. Secondary Outcome

Title	Correlation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) Counts
Description	The Friedman test will be used to evaluate correlations between microRNA measures (CT) and Baseline CTCs.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Among the 50 patients in this biomarker substudy, 14 patients were excluded: 1 ineligible for S0925, 6 started LHRH therapy prior to registration, 3 had insufficient miRNA samples and 4 had insufficient CTC samples. The remaining 36 patients were used in this analysis.

Arm/Group Title	CTC=0	CTC= 1-4	CTC= 5+
Arm/Group Description	No CTCs foundin 7.5 mL blood sample collected at baseline, pooled treatment arms	1 to 4 CTCs found in 7.5 mL blood sample collected at baseline, pooled treatment arms	Five or more CTCs were found in 7.5 mL blood sample collected at baseline, pooled treatment arms
Measure Participants	14	8	14
miR-141	33.0	32.7	31.9
miR-200a	34.4	34.7	33.0
miR-200b	33.4	33.2	33.6
miR-210	32.5	32.7	32.1
miR-375	32.8	32.7	30.2

7. Secondary Outcome

Title	Change in Level of CTCs
Description	Will be correlated with 28-week PSA response.
Time Frame	Baseline to 28 weeks

Outcome Measure Data

Analysis Population Description

Among the 50 patients in this biomarker substudy, 1 was ineligible for the trial, 6 started LHRH therapy prior to registration, and 4 had CTC blood samples that were not assay evaluable. The remaining 39 patients were included in this analysis.

Arm/Group Title	CTC=0	CTC= 1-4	CTC= 5+
Arm/Group Description	No CTCs foundin 7.5 mL blood sample collected at baseline, pooled treatment arms	1 to 4 CTCs found in 7.5 mL blood sample collected at baseline, pooled treatment arms	Five or more CTCs were found in 7.5 mL blood sample collected at baseline, pooled treatment arms
Measure Participants	16	9	14
PSA <= 0.2 ng/mL	12 11.4%	5 4.8%	4 1.9%
0.2 < PSA <=4.0 ng/mL	0 0%	2 1.9%	3 1.4%
PSA > 4.0 ng/mL	4 3.8%	2 1.9%	7 3.3%

8. Other Pre-specified Outcome

Title	Change in Level of IGF-I, Free IGF-I and C-peptide
Description	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.
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Androgen Deprivation and Cixutumumab)	Arm II (Androgen Deprivation Therapy)
Arm/Group Description	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. Bicalutamide: Given PO Cixutumumab: Given IV Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Pharmacological Study: Correlative studies	Patients receive androgen deprivation therapy comprising bicalutamide and either goserelin acetate or leuprolide acetate as in arm I. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Pharmacological Study: Correlative studies
Measure Participants	18	9
C-peptide	-7 (24.5)	3 (20.1)
IGF-I	0 (2.4)	1 (2.7)
IGF-II	10 (46.7)	-6 (43.7)

9. Other Pre-specified Outcome

Title	Change in Level of IGFBP2, IGFBP3 and Growth Hormone
Description	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.
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Androgen Deprivation and Cixutumumab)	Arm II (Androgen Deprivation Therapy)
Arm/Group Description	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. Bicalutamide: Given PO Cixutumumab: Given IV Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Pharmacological Study: Correlative studies	Patients receive androgen deprivation therapy comprising bicalutamide and either goserelin acetate or leuprolide acetate as in arm I. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Pharmacological Study: Correlative studies
Measure Participants	18	9
IGFBP-I	-946 (2309.3)	-904 (32362.4)
IGFBP-III	13893 (47335.2)	291 (13344.5)
GH	66 (159.9)	-25 (327.8)

10. Other Pre-specified Outcome

Title	Change in Level of Insulin
Description	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.
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Androgen Deprivation and Cixutumumab)	Arm II (Androgen Deprivation Therapy)
Arm/Group Description	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. Bicalutamide: Given PO Cixutumumab: Given IV Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Pharmacological Study: Correlative studies	Patients receive androgen deprivation therapy comprising bicalutamide and either goserelin acetate or leuprolide acetate as in arm I. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Pharmacological Study: Correlative studies
Measure Participants	18	9
Mean (Standard Deviation) [ulU/mL]	0 (5.1)	0 (1.5)

Adverse Events

Time Frame	Up to 28 weeks
Adverse Event Reporting Description	Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Arm/Group Title	Arm I (Androgen Deprivation and Cixutumumab)		Arm II (Androgen Deprivation Therapy)
Arm/Group Description	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. Bicalutamide: Given PO Cixutumumab: Given IV Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Pharmacological Study: Correlative studies		Patients receive androgen deprivation therapy comprising bicalutamide and either goserelin acetate or leuprolide acetate as in arm I. Bicalutamide: Given PO Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Pharmacological Study: Correlative studies
All Cause Mortality
	Arm I (Androgen Deprivation and Cixutumumab)		Arm II (Androgen Deprivation Therapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (Androgen Deprivation and Cixutumumab)		Arm II (Androgen Deprivation Therapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/101 (9.9%)		4/104 (3.8%)
Blood and lymphatic system disorders
Anemia	1/101 (1%)		0/104 (0%)
Cardiac disorders
Left ventricular systolic dysfunction	1/101 (1%)		0/104 (0%)
Gastrointestinal disorders
Colonic obstruction	1/101 (1%)		0/104 (0%)
Dry mouth	1/101 (1%)		0/104 (0%)
Duodenal ulcer	1/101 (1%)		0/104 (0%)
Dysphagia	1/101 (1%)		0/104 (0%)
Gastric hemorrhage	1/101 (1%)		0/104 (0%)
Mucositis oral	1/101 (1%)		0/104 (0%)
Nausea	1/101 (1%)		0/104 (0%)
Vomiting	2/101 (2%)		0/104 (0%)
General disorders
Death NOS	0/101 (0%)		2/104 (1.9%)
Malaise	1/101 (1%)		0/104 (0%)
Pain	1/101 (1%)		0/104 (0%)
Infections and infestations
Soft tissue infection	1/101 (1%)		0/104 (0%)
Tooth infection	1/101 (1%)		0/104 (0%)
Urinary tract infection	1/101 (1%)		0/104 (0%)
Injury, poisoning and procedural complications
Fracture	1/101 (1%)		0/104 (0%)
Metabolism and nutrition disorders
Hypercalcemia	1/101 (1%)		0/104 (0%)
Hyperglycemia	1/101 (1%)		0/104 (0%)
Hypocalcemia	1/101 (1%)		0/104 (0%)
Musculoskeletal and connective tissue disorders
Exostosis	1/101 (1%)		0/104 (0%)
Nervous system disorders
Cognitive disturbance	1/101 (1%)		0/104 (0%)
Stroke	0/101 (0%)		1/104 (1%)
Renal and urinary disorders
Urinary tract obstruction	1/101 (1%)		0/104 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	0/101 (0%)		1/104 (1%)
Vascular disorders
Thromboembolic event	1/101 (1%)		0/104 (0%)
Other (Not Including Serious) Adverse Events
	Arm I (Androgen Deprivation and Cixutumumab)		Arm II (Androgen Deprivation Therapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	101/101 (100%)		94/104 (90.4%)
Blood and lymphatic system disorders
Anemia	39/101 (38.6%)		30/104 (28.8%)
Ear and labyrinth disorders
Tinnitus	6/101 (5.9%)		1/104 (1%)
Eye disorders
Blurred vision	11/101 (10.9%)		4/104 (3.8%)
Flashing lights	8/101 (7.9%)		0/104 (0%)
Gastrointestinal disorders
Abdominal pain	11/101 (10.9%)		9/104 (8.7%)
Constipation	17/101 (16.8%)		9/104 (8.7%)
Diarrhea	24/101 (23.8%)		8/104 (7.7%)
Dry mouth	10/101 (9.9%)		1/104 (1%)
Nausea	16/101 (15.8%)		6/104 (5.8%)
Oral pain	10/101 (9.9%)		0/104 (0%)
Vomiting	7/101 (6.9%)		5/104 (4.8%)
General disorders
Chills	6/101 (5.9%)		3/104 (2.9%)
Edema limbs	9/101 (8.9%)		8/104 (7.7%)
Fatigue	66/101 (65.3%)		47/104 (45.2%)
Flu like symptoms	9/101 (8.9%)		0/104 (0%)
Pain	24/101 (23.8%)		21/104 (20.2%)
Infections and infestations
Urinary tract infection	6/101 (5.9%)		2/104 (1.9%)
Injury, poisoning and procedural complications
Bruising	10/101 (9.9%)		1/104 (1%)
Investigations
Alanine aminotransferase increased	19/101 (18.8%)		14/104 (13.5%)
Alkaline phosphatase increased	10/101 (9.9%)		16/104 (15.4%)
Aspartate aminotransferase increased	15/101 (14.9%)		14/104 (13.5%)
Blood bilirubin increased	6/101 (5.9%)		3/104 (2.9%)
Creatinine increased	24/101 (23.8%)		12/104 (11.5%)
Lymphocyte count decreased	3/101 (3%)		10/104 (9.6%)
Neutrophil count decreased	14/101 (13.9%)		4/104 (3.8%)
Platelet count decreased	33/101 (32.7%)		5/104 (4.8%)
Weight gain	4/101 (4%)		7/104 (6.7%)
Weight loss	11/101 (10.9%)		2/104 (1.9%)
White blood cell decreased	7/101 (6.9%)		9/104 (8.7%)
Metabolism and nutrition disorders
Anorexia	12/101 (11.9%)		8/104 (7.7%)
Hypercalcemia	11/101 (10.9%)		4/104 (3.8%)
Hyperglycemia	55/101 (54.5%)		25/104 (24%)
Hyperkalemia	8/101 (7.9%)		5/104 (4.8%)
Hypocalcemia	5/101 (5%)		6/104 (5.8%)
Hypoglycemia	2/101 (2%)		6/104 (5.8%)
Hypokalemia	3/101 (3%)		8/104 (7.7%)
Hyponatremia	8/101 (7.9%)		7/104 (6.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	18/101 (17.8%)		15/104 (14.4%)
Arthritis	7/101 (6.9%)		3/104 (2.9%)
Back pain	30/101 (29.7%)		20/104 (19.2%)
Bone pain	13/101 (12.9%)		13/104 (12.5%)
Flank pain	7/101 (6.9%)		5/104 (4.8%)
Generalized muscle weakness	8/101 (7.9%)		3/104 (2.9%)
Muscle weakness lower limb	6/101 (5.9%)		2/104 (1.9%)
Myalgia	17/101 (16.8%)		7/104 (6.7%)
Pain in extremity	14/101 (13.9%)		9/104 (8.7%)
Nervous system disorders
Dizziness	23/101 (22.8%)		9/104 (8.7%)
Dysgeusia	13/101 (12.9%)		0/104 (0%)
Headache	12/101 (11.9%)		4/104 (3.8%)
Peripheral sensory neuropathy	9/101 (8.9%)		5/104 (4.8%)
Psychiatric disorders
Anxiety	8/101 (7.9%)		7/104 (6.7%)
Depression	10/101 (9.9%)		7/104 (6.7%)
Insomnia	8/101 (7.9%)		10/104 (9.6%)
Libido decreased	3/101 (3%)		9/104 (8.7%)
Renal and urinary disorders
Hematuria	10/101 (9.9%)		6/104 (5.8%)
Urinary frequency	24/101 (23.8%)		18/104 (17.3%)
Urinary incontinence	11/101 (10.9%)		2/104 (1.9%)
Urinary urgency	6/101 (5.9%)		4/104 (3.8%)
Reproductive system and breast disorders
Erectile dysfunction	5/101 (5%)		12/104 (11.5%)
Pelvic pain	8/101 (7.9%)		3/104 (2.9%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	7/101 (6.9%)		2/104 (1.9%)
Cough	6/101 (5.9%)		4/104 (3.8%)
Dyspnea	4/101 (4%)		6/104 (5.8%)
Skin and subcutaneous tissue disorders
Dry skin	21/101 (20.8%)		2/104 (1.9%)
Pruritus	11/101 (10.9%)		4/104 (3.8%)
Rash maculo-papular	10/101 (9.9%)		3/104 (2.9%)
Skin and subcutaneous tissue disorders - Other	9/101 (8.9%)		0/104 (0%)
Vascular disorders
Hot flashes	49/101 (48.5%)		69/104 (66.3%)
Hypertension	27/101 (26.7%)		25/104 (24%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.