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

• ClinicalTrials.gov Identifier: NCT01120236
• Recruitment Status: Completed
• First Posted: May 10, 2010
• Results First Posted: October 6, 2016
• Last Update Posted: February 26, 2018
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Prostate Adenocarcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer
• Interventions: Drug: Bicalutamide; Biological: Cixutumumab; Drug: Goserelin Acetate; Other: Laboratory Biomarker Analysis; Drug: Leuprolide Acetate; Other: Pharmacological Study
• Enrollment: 211

Participant Flow

Recruitment Details
Pre-assignment Details

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 [1]
Completed	105	105
Not Completed	0	1
[1] Patient ineligible due to no demonstable radiographic metastasis and is excluded from all analyses.

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 Number of Baseline Participants		105	105	210
Baseline 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.
Age, Continuous; Median (Inter-Quartile Range); Unit of measure: Years
	Number Analyzed	105 participants	105 participants	210 participants
		65; (60 to 72)	66; (58 to 73)	66; (59 to 73)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	105 participants	105 participants	210 participants
	Female	0 0.0%	0 0.0%	0 0.0%
	Male	105 100.0%	105 100.0%	210 100.0%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	105 participants	105 participants	210 participants
Black		4	10	14
White		94	88	182
Other		7	7	14
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	105 participants	105 participants	210 participants
		105	105	210
Prostate-Specific Antigen (PSA); Median (Inter-Quartile Range); Unit of measure: ng/mL
	Number Analyzed	105 participants	105 participants	210 participants
		31; (12 to 74)	37; (10 to 200)	34; (11 to 133)
Weight; Median (Inter-Quartile Range); Unit of measure: Kg
	Number Analyzed	105 participants	105 participants	210 participants
		90; (79 to 101)	86; (77 to 98)	88; (77 to 100)
Body Mass Index (BMI); Measure Type: Number; Unit of measure: Participants	Number Analyzed	105 participants	105 participants	210 participants
<18.5 (underweight)		1	2	3
18.5 to 24.9 (normal weight)		21	29	50
25 to 29.9 (overweight)		36	39	75
>= 30 (obese)		43	33	76
Unknown		4	2	6
Gleason Score [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	105 participants	105 participants	210 participants
<7		8	6	14
7		29	11	40
>=7		63	82	145
Unknown		5	6	11
		[1] Measure Description: This is a 2 to 10 grading system for prostate carcinoma devised by Dr. Donald Gleason in 1977 as a method for predicting the behavior of prostate cancer. Tumors with a low Gleason score are less likely to show aggressive behavior and therefore are less likely to have spread outside of the gland to lymph nodes. To obtain a Gleason score, the dominant tumor pattern is added to the second most prevalent pattern to obtain a number between 2 and 10. If a tumor has patterns 3 and 2, the score would be 5. If the tumor has only one pattern, then the single pattern is added to itself (e.g. 3+3=6).
Zubrod Performance Score [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	105 participants	105 participants	210 participants
0		62	65	127
1		41	38	79
2		2	2	4
		[1] Measure Description: Scale 0 (best) to 2 (worst) 0 = Fully active, able to carry on all pre-disease performance without restriction.; = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work.; = Ambulatory and capable of self-care but unable to carry out any work activities; up and about more than 50% of waking hours.
Site of Metastasis; Measure Type: Number; Unit of measure: Participants	Number Analyzed	105 participants	105 participants	210 participants
Lymph Node Only		15	9	24
Bone Only		56	63	119
Lymph Node and Bone		19	17	36
Visceral		15	16	31
Bone Pain; Measure Type: Number; Unit of measure: Participants
	Number Analyzed	105 participants	105 participants	210 participants
		28	35	63
Early Induction Androgen Deprivation [1]; Measure Type: Number; Unit of measure: Participants
	Number Analyzed	105 participants	105 participants	210 participants
		59	65	124
		[1] Measure Description: Prior remote AD was allowed only if received in the neoadjuvant, concurrent, and/or adjuvant settings and > 2 years had elapsed since completion of therapy.

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
Overall Number of Participants Analyzed	105	105
Measure Type: Number; Unit of Measure: participants
	42	34

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.16
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.24
	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
Overall Number of Participants Analyzed	101	104
Measure Type: Number; Unit of Measure: Participants
Alanine aminotransferase increased	1	0
Anemia	1	1
Anxiety	0	1
Aspartate aminotransferase increased	1	0
Cognitive disturbance	1	0
Depression	0	1
Erectile dysfunction	1	0
Exostosis	1	0
Glucose intolerance	0	1
Hot flashes	1	1
Hypercalcemia	2	0
Hyperglycemia	8	0
Hypertension	2	2
Hypertriglyceridemia	1	0
Left ventricular systolic dysfunction	1	0
Nausea	1	0
Obesity	1	1
Soft tissue infection	1	0
Urinary tract infection	1	0
Urinary tract obstruction	0	1
Vomiting	1	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
Overall Number of Participants Analyzed	105	105
Measure Type: Number; Unit of Measure: participants
	46	56

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	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.11
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.82
	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
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

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)
Overall Number of Participants Analyzed	22	5	13
Median (Full Range); Unit of Measure: Cycle Threshold (CT)
miR-141	32.6; (29.5 to 36.8)	32.0; (31.9 to 32.7)	31.5; (27.6 to 33.5)
miR-200a	34.5; (31.4 to 39.9)	33.8; (32.4 to 35.6)	33.8; (30.1 to 40.0)
miR-200b	33.6; (32.7 to 35.0)	33.6; (32.7 to 35.0)	32.6; (29.3 to 34.8)
miR-210	32.5; (30.8 to 36.8)	32.1; (31.3 to 33.8)	32.3; (28.0 to 34.3)
miR-375	33.0; (29.3 to 35.9)	32.6; (30.0 to 35.0)	29.5; (25.7 to 33.8)

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
Overall Number of Participants Analyzed	14	8	14
Median (Full Range); Unit of Measure: Cycle Threshold (CT)
miR-141	33.0; (31.5 to 36.8)	32.7; (31.6 to 33.7)	31.9; (28.8 to 32.5)
miR-200a	34.4; (31.4 to 39.7)	34.7; (32.1 to 37.7)	33.0; (30.1 to 40.0)
miR-200b	33.4; (32.1 to 34.2)	33.2; (32.7 to 34.1)	33.6; (29.3 to 35.0)
miR-210	32.5; (30.8 to 36.8)	32.7; (31.4 to 34.3)	32.1; (31.0 to 33.5)
miR-375	32.8; (30.1 to 35.1)	32.7; (26.5 to 35.9)	30.2; (26.7 to 35.0)

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
Overall Number of Participants Analyzed	16	9	14
Measure Type: Count of Participants; Unit of Measure: Participants
PSA <= 0.2 ng/mL	12 75.0%	5 55.6%	4 28.6%
0.2 < PSA <=4.0 ng/mL	0 0.0%	2 22.2%	3 21.4%
PSA > 4.0 ng/mL	4 25.0%	2 22.2%	7 50.0%

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
Overall Number of Participants Analyzed	18	9
Mean (Standard Deviation); Unit of Measure: ng/mL
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
Overall Number of Participants Analyzed	18	9
Mean (Standard Deviation); Unit of Measure: pg/mL
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
Overall Number of Participants Analyzed	18	9
Mean (Standard Deviation); Unit of Measure: 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 (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Arm I (Androgen Deprivation and Cixutumumab)	Arm II (Androgen Deprivation Therapy)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	10/101 (9.90%)	4/104 (3.85%)
Blood and lymphatic system disorders
Anemia †	1/101 (0.99%)	0/104 (0.00%)
Cardiac disorders
Left ventricular systolic dysfunction †	1/101 (0.99%)	0/104 (0.00%)
Gastrointestinal disorders
Colonic obstruction †	1/101 (0.99%)	0/104 (0.00%)
Dry mouth †	1/101 (0.99%)	0/104 (0.00%)
Duodenal ulcer †	1/101 (0.99%)	0/104 (0.00%)
Dysphagia †	1/101 (0.99%)	0/104 (0.00%)
Gastric hemorrhage †	1/101 (0.99%)	0/104 (0.00%)
Mucositis oral †	1/101 (0.99%)	0/104 (0.00%)
Nausea †	1/101 (0.99%)	0/104 (0.00%)
Vomiting †	2/101 (1.98%)	0/104 (0.00%)
General disorders
Death NOS †	0/101 (0.00%)	2/104 (1.92%)
Malaise †	1/101 (0.99%)	0/104 (0.00%)
Pain †	1/101 (0.99%)	0/104 (0.00%)
Infections and infestations
Soft tissue infection †	1/101 (0.99%)	0/104 (0.00%)
Tooth infection †	1/101 (0.99%)	0/104 (0.00%)
Urinary tract infection †	1/101 (0.99%)	0/104 (0.00%)
Injury, poisoning and procedural complications
Fracture †	1/101 (0.99%)	0/104 (0.00%)
Metabolism and nutrition disorders
Hypercalcemia †	1/101 (0.99%)	0/104 (0.00%)
Hyperglycemia †	1/101 (0.99%)	0/104 (0.00%)
Hypocalcemia †	1/101 (0.99%)	0/104 (0.00%)
Musculoskeletal and connective tissue disorders
Exostosis †	1/101 (0.99%)	0/104 (0.00%)
Nervous system disorders
Cognitive disturbance †	1/101 (0.99%)	0/104 (0.00%)
Stroke †	0/101 (0.00%)	1/104 (0.96%)
Renal and urinary disorders
Urinary tract obstruction †	1/101 (0.99%)	0/104 (0.00%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure †	0/101 (0.00%)	1/104 (0.96%)
Vascular disorders
Thromboembolic event †	1/101 (0.99%)	0/104 (0.00%)
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm I (Androgen Deprivation and Cixutumumab)	Arm II (Androgen Deprivation Therapy)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	101/101 (100.00%)	94/104 (90.38%)
Blood and lymphatic system disorders
Anemia †	39/101 (38.61%)	30/104 (28.85%)
Ear and labyrinth disorders
Tinnitus †	6/101 (5.94%)	1/104 (0.96%)
Eye disorders
Blurred vision †	11/101 (10.89%)	4/104 (3.85%)
Flashing lights †	8/101 (7.92%)	0/104 (0.00%)
Gastrointestinal disorders
Abdominal pain †	11/101 (10.89%)	9/104 (8.65%)
Constipation †	17/101 (16.83%)	9/104 (8.65%)
Diarrhea †	24/101 (23.76%)	8/104 (7.69%)
Dry mouth †	10/101 (9.90%)	1/104 (0.96%)
Nausea †	16/101 (15.84%)	6/104 (5.77%)
Oral pain †	10/101 (9.90%)	0/104 (0.00%)
Vomiting †	7/101 (6.93%)	5/104 (4.81%)
General disorders
Chills †	6/101 (5.94%)	3/104 (2.88%)
Edema limbs †	9/101 (8.91%)	8/104 (7.69%)
Fatigue †	66/101 (65.35%)	47/104 (45.19%)
Flu like symptoms †	9/101 (8.91%)	0/104 (0.00%)
Pain †	24/101 (23.76%)	21/104 (20.19%)
Infections and infestations
Urinary tract infection †	6/101 (5.94%)	2/104 (1.92%)
Injury, poisoning and procedural complications
Bruising †	10/101 (9.90%)	1/104 (0.96%)
Investigations
Alanine aminotransferase increased †	19/101 (18.81%)	14/104 (13.46%)
Alkaline phosphatase increased †	10/101 (9.90%)	16/104 (15.38%)
Aspartate aminotransferase increased †	15/101 (14.85%)	14/104 (13.46%)
Blood bilirubin increased †	6/101 (5.94%)	3/104 (2.88%)
Creatinine increased †	24/101 (23.76%)	12/104 (11.54%)
Lymphocyte count decreased †	3/101 (2.97%)	10/104 (9.62%)
Neutrophil count decreased †	14/101 (13.86%)	4/104 (3.85%)
Platelet count decreased †	33/101 (32.67%)	5/104 (4.81%)
Weight gain †	4/101 (3.96%)	7/104 (6.73%)
Weight loss †	11/101 (10.89%)	2/104 (1.92%)
White blood cell decreased †	7/101 (6.93%)	9/104 (8.65%)
Metabolism and nutrition disorders
Anorexia †	12/101 (11.88%)	8/104 (7.69%)
Hypercalcemia †	11/101 (10.89%)	4/104 (3.85%)
Hyperglycemia †	55/101 (54.46%)	25/104 (24.04%)
Hyperkalemia †	8/101 (7.92%)	5/104 (4.81%)
Hypocalcemia †	5/101 (4.95%)	6/104 (5.77%)
Hypoglycemia †	2/101 (1.98%)	6/104 (5.77%)
Hypokalemia †	3/101 (2.97%)	8/104 (7.69%)
Hyponatremia †	8/101 (7.92%)	7/104 (6.73%)
Musculoskeletal and connective tissue disorders
Arthralgia †	18/101 (17.82%)	15/104 (14.42%)
Arthritis †	7/101 (6.93%)	3/104 (2.88%)
Back pain †	30/101 (29.70%)	20/104 (19.23%)
Bone pain †	13/101 (12.87%)	13/104 (12.50%)
Flank pain †	7/101 (6.93%)	5/104 (4.81%)
Generalized muscle weakness †	8/101 (7.92%)	3/104 (2.88%)
Muscle weakness lower limb †	6/101 (5.94%)	2/104 (1.92%)
Myalgia †	17/101 (16.83%)	7/104 (6.73%)
Pain in extremity †	14/101 (13.86%)	9/104 (8.65%)
Nervous system disorders
Dizziness †	23/101 (22.77%)	9/104 (8.65%)
Dysgeusia †	13/101 (12.87%)	0/104 (0.00%)
Headache †	12/101 (11.88%)	4/104 (3.85%)
Peripheral sensory neuropathy †	9/101 (8.91%)	5/104 (4.81%)
Psychiatric disorders
Anxiety †	8/101 (7.92%)	7/104 (6.73%)
Depression †	10/101 (9.90%)	7/104 (6.73%)
Insomnia †	8/101 (7.92%)	10/104 (9.62%)
Libido decreased †	3/101 (2.97%)	9/104 (8.65%)
Renal and urinary disorders
Hematuria †	10/101 (9.90%)	6/104 (5.77%)
Urinary frequency †	24/101 (23.76%)	18/104 (17.31%)
Urinary incontinence †	11/101 (10.89%)	2/104 (1.92%)
Urinary urgency †	6/101 (5.94%)	4/104 (3.85%)
Reproductive system and breast disorders
Erectile dysfunction †	5/101 (4.95%)	12/104 (11.54%)
Pelvic pain †	8/101 (7.92%)	3/104 (2.88%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis †	7/101 (6.93%)	2/104 (1.92%)
Cough †	6/101 (5.94%)	4/104 (3.85%)
Dyspnea †	4/101 (3.96%)	6/104 (5.77%)
Skin and subcutaneous tissue disorders
Dry skin †	21/101 (20.79%)	2/104 (1.92%)
Pruritus †	11/101 (10.89%)	4/104 (3.85%)
Rash maculo-papular †	10/101 (9.90%)	3/104 (2.88%)
Skin and subcutaneous tissue disorders - Other †	9/101 (8.91%)	0/104 (0.00%)
Vascular disorders
Hot flashes †	49/101 (48.51%)	69/104 (66.35%)
Hypertension †	27/101 (26.73%)	25/104 (24.04%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Evan Y. Yu, MD
• Organization: Department of Medicine, Division of Oncology, University of Washington
• EMail: evenyu@u.washington.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01120236
• Other Study ID Numbers: NCI-2011-02003; NCI-2011-02003 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); SWOG-S0925; CDR0000663832; S0925 ( Other Identifier: SWOG ); S0925 ( Other Identifier: CTEP ); U10CA032102 ( U.S. NIH Grant/Contract )
• First Submitted: May 7, 2010
• First Posted: May 10, 2010
• Results First Submitted: April 18, 2016
• Results First Posted: October 6, 2016
• Last Update Posted: February 26, 2018