Trial Outcomes & Findings for Bicalutamide and Goserelin or Leuprolide Acetate With or Without Cixutumumab in Treating Patients With Newly Diagnosed Metastatic Prostate Cancer (NCT NCT01120236)

NCT ID: NCT01120236

Last Updated: 2018-02-26

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

211 participants

Primary outcome timeframe

7 months

Results posted on

2018-02-26

Participant Flow

Participant milestones

Participant milestones
Measure	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. Bicalutamide: Given PO Cixutumumab: Given IV Goserelin Acetate: Given SC Laboratory Biomarker Analysis: Correlative studies Leuprolide Acetate: Given IM Pharmacological Study: Correlative studies	Arm II (Androgen Deprivation Therapy) 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 Study STARTED	105	106
Overall Study Ineligble	0	1
Overall Study COMPLETED	105	105
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Androgen Deprivation and Cixutumumab) n=105 Participants 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	Arm II (Androgen Deprivation Therapy) n=105 Participants 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 n=210 Participants Total of all reporting groups
Age, Continuous	65 years n=5 Participants	66 years n=7 Participants	66 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	105 Participants n=5 Participants	105 Participants n=7 Participants	210 Participants n=5 Participants
Race/Ethnicity, Customized Black	4 participants n=5 Participants	10 participants n=7 Participants	14 participants n=5 Participants
Race/Ethnicity, Customized White	94 participants n=5 Participants	88 participants n=7 Participants	182 participants n=5 Participants
Race/Ethnicity, Customized Other	7 participants n=5 Participants	7 participants n=7 Participants	14 participants n=5 Participants
Region of Enrollment United States	105 participants n=5 Participants	105 participants n=7 Participants	210 participants n=5 Participants
Prostate-Specific Antigen (PSA)	31 ng/mL n=5 Participants	37 ng/mL n=7 Participants	34 ng/mL n=5 Participants
Weight	90 kg n=5 Participants	86 kg n=7 Participants	88 kg n=5 Participants
Body Mass Index (BMI) <18.5 (underweight)	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Body Mass Index (BMI) 18.5 to 24.9 (normal weight)	21 participants n=5 Participants	29 participants n=7 Participants	50 participants n=5 Participants
Body Mass Index (BMI) 25 to 29.9 (overweight)	36 participants n=5 Participants	39 participants n=7 Participants	75 participants n=5 Participants
Body Mass Index (BMI) >= 30 (obese)	43 participants n=5 Participants	33 participants n=7 Participants	76 participants n=5 Participants
Body Mass Index (BMI) Unknown	4 participants n=5 Participants	2 participants n=7 Participants	6 participants n=5 Participants
Gleason Score <7	8 participants n=5 Participants	6 participants n=7 Participants	14 participants n=5 Participants
Gleason Score 7	29 participants n=5 Participants	11 participants n=7 Participants	40 participants n=5 Participants
Gleason Score >=7	63 participants n=5 Participants	82 participants n=7 Participants	145 participants n=5 Participants
Gleason Score Unknown	5 participants n=5 Participants	6 participants n=7 Participants	11 participants n=5 Participants
Zubrod Performance Score 0	62 participants n=5 Participants	65 participants n=7 Participants	127 participants n=5 Participants
Zubrod Performance Score 1	41 participants n=5 Participants	38 participants n=7 Participants	79 participants n=5 Participants
Zubrod Performance Score 2	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Site of Metastasis Lymph Node Only	15 participants n=5 Participants	9 participants n=7 Participants	24 participants n=5 Participants
Site of Metastasis Bone Only	56 participants n=5 Participants	63 participants n=7 Participants	119 participants n=5 Participants
Site of Metastasis Lymph Node and Bone	19 participants n=5 Participants	17 participants n=7 Participants	36 participants n=5 Participants
Site of Metastasis Visceral	15 participants n=5 Participants	16 participants n=7 Participants	31 participants n=5 Participants
Bone Pain	28 participants n=5 Participants	35 participants n=7 Participants	63 participants n=5 Participants
Early Induction Androgen Deprivation	59 participants n=5 Participants	65 participants n=7 Participants	124 participants n=5 Participants

PRIMARY outcome

Timeframe: 7 months

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

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

Outcome measures

Outcome measures
Measure	Arm I (Androgen Deprivation and Cixutumumab) n=105 Participants 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	Arm II (Androgen Deprivation Therapy) n=105 Participants 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	PSA Non-Responders 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)
Undetectable PSA Rate	42 participants	34 participants	—

SECONDARY outcome

Timeframe: Up to 28 weeks

Population: 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.

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

Outcome measures

Outcome measures
Measure	Arm I (Androgen Deprivation and Cixutumumab) n=101 Participants 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	Arm II (Androgen Deprivation Therapy) n=104 Participants 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	PSA Non-Responders 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)
Toxicity Alanine aminotransferase increased	1 Participants	0 Participants	—
Toxicity Anemia	1 Participants	1 Participants	—
Toxicity Anxiety	0 Participants	1 Participants	—
Toxicity Aspartate aminotransferase increased	1 Participants	0 Participants	—
Toxicity Cognitive disturbance	1 Participants	0 Participants	—
Toxicity Depression	0 Participants	1 Participants	—
Toxicity Erectile dysfunction	1 Participants	0 Participants	—
Toxicity Exostosis	1 Participants	0 Participants	—
Toxicity Glucose intolerance	0 Participants	1 Participants	—
Toxicity Hot flashes	1 Participants	1 Participants	—
Toxicity Hypercalcemia	2 Participants	0 Participants	—
Toxicity Hyperglycemia	8 Participants	0 Participants	—
Toxicity Hypertension	2 Participants	2 Participants	—
Toxicity Hypertriglyceridemia	1 Participants	0 Participants	—
Toxicity Left ventricular systolic dysfunction	1 Participants	0 Participants	—
Toxicity Nausea	1 Participants	0 Participants	—
Toxicity Obesity	1 Participants	1 Participants	—
Toxicity Soft tissue infection	1 Participants	0 Participants	—
Toxicity Urinary tract infection	1 Participants	0 Participants	—
Toxicity Urinary tract obstruction	0 Participants	1 Participants	—
Toxicity Vomiting	1 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Up to 5 years

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

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

Outcome measures

Outcome measures
Measure	Arm I (Androgen Deprivation and Cixutumumab) n=105 Participants 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	Arm II (Androgen Deprivation Therapy) n=105 Participants 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	PSA Non-Responders 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)
Proportion of Patients Who do Not Achieve a Partial PSA Response	46 participants	56 participants	—

SECONDARY outcome

Timeframe: Up to 5 years

Population: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to 28 weeks

Population: 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.

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

Outcome measures

Outcome measures
Measure	Arm I (Androgen Deprivation and Cixutumumab) n=22 Participants 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	Arm II (Androgen Deprivation Therapy) n=5 Participants 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	PSA Non-Responders n=13 Participants 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)
Correlation of microRNA Measures With 28-week PSA Response miR-141	32.6 Cycle Threshold (CT) Interval 29.5 to 36.8	32.0 Cycle Threshold (CT) Interval 31.9 to 32.7	31.5 Cycle Threshold (CT) Interval 27.6 to 33.5
Correlation of microRNA Measures With 28-week PSA Response miR-200a	34.5 Cycle Threshold (CT) Interval 31.4 to 39.9	33.8 Cycle Threshold (CT) Interval 32.4 to 35.6	33.8 Cycle Threshold (CT) Interval 30.1 to 40.0
Correlation of microRNA Measures With 28-week PSA Response miR-200b	33.6 Cycle Threshold (CT) Interval 32.7 to 35.0	33.6 Cycle Threshold (CT) Interval 32.7 to 35.0	32.6 Cycle Threshold (CT) Interval 29.3 to 34.8
Correlation of microRNA Measures With 28-week PSA Response miR-210	32.5 Cycle Threshold (CT) Interval 30.8 to 36.8	32.1 Cycle Threshold (CT) Interval 31.3 to 33.8	32.3 Cycle Threshold (CT) Interval 28.0 to 34.3
Correlation of microRNA Measures With 28-week PSA Response miR-375	33.0 Cycle Threshold (CT) Interval 29.3 to 35.9	32.6 Cycle Threshold (CT) Interval 30.0 to 35.0	29.5 Cycle Threshold (CT) Interval 25.7 to 33.8

SECONDARY outcome

Timeframe: Baseline

Population: 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.

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

Outcome measures

Outcome measures
Measure	Arm I (Androgen Deprivation and Cixutumumab) n=14 Participants 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	Arm II (Androgen Deprivation Therapy) n=8 Participants 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	PSA Non-Responders n=14 Participants 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)
Correlation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) Counts miR-375	32.8 Cycle Threshold (CT) Interval 30.1 to 35.1	32.7 Cycle Threshold (CT) Interval 26.5 to 35.9	30.2 Cycle Threshold (CT) Interval 26.7 to 35.0
Correlation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) Counts miR-141	33.0 Cycle Threshold (CT) Interval 31.5 to 36.8	32.7 Cycle Threshold (CT) Interval 31.6 to 33.7	31.9 Cycle Threshold (CT) Interval 28.8 to 32.5
Correlation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) Counts miR-200a	34.4 Cycle Threshold (CT) Interval 31.4 to 39.7	34.7 Cycle Threshold (CT) Interval 32.1 to 37.7	33.0 Cycle Threshold (CT) Interval 30.1 to 40.0
Correlation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) Counts miR-200b	33.4 Cycle Threshold (CT) Interval 32.1 to 34.2	33.2 Cycle Threshold (CT) Interval 32.7 to 34.1	33.6 Cycle Threshold (CT) Interval 29.3 to 35.0
Correlation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) Counts miR-210	32.5 Cycle Threshold (CT) Interval 30.8 to 36.8	32.7 Cycle Threshold (CT) Interval 31.4 to 34.3	32.1 Cycle Threshold (CT) Interval 31.0 to 33.5

SECONDARY outcome

Timeframe: Baseline to 28 weeks

Population: 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.

Will be correlated with 28-week PSA response.

Outcome measures

Outcome measures
Measure	Arm I (Androgen Deprivation and Cixutumumab) n=16 Participants 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	Arm II (Androgen Deprivation Therapy) n=9 Participants 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	PSA Non-Responders n=14 Participants 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)
Change in Level of CTCs PSA <= 0.2 ng/mL	12 Participants	5 Participants	4 Participants
Change in Level of CTCs 0.2 < PSA <=4.0 ng/mL	0 Participants	2 Participants	3 Participants
Change in Level of CTCs PSA > 4.0 ng/mL	4 Participants	2 Participants	7 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Arm I (Androgen Deprivation and Cixutumumab) n=18 Participants 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	Arm II (Androgen Deprivation Therapy) n=9 Participants 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	PSA Non-Responders 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)
Change in Level of IGF-I, Free IGF-I and C-peptide IGF-II	10 ng/mL Standard Deviation 46.7	-6 ng/mL Standard Deviation 43.7	—
Change in Level of IGF-I, Free IGF-I and C-peptide C-peptide	-7 ng/mL Standard Deviation 24.5	3 ng/mL Standard Deviation 20.1	—
Change in Level of IGF-I, Free IGF-I and C-peptide IGF-I	0 ng/mL Standard Deviation 2.4	1 ng/mL Standard Deviation 2.7	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Arm I (Androgen Deprivation and Cixutumumab) n=18 Participants 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	Arm II (Androgen Deprivation Therapy) n=9 Participants 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	PSA Non-Responders 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)
Change in Level of IGFBP2, IGFBP3 and Growth Hormone IGFBP-I	-946 pg/mL Standard Deviation 2309.3	-904 pg/mL Standard Deviation 32362.4	—
Change in Level of IGFBP2, IGFBP3 and Growth Hormone IGFBP-III	13893 pg/mL Standard Deviation 47335.2	291 pg/mL Standard Deviation 13344.5	—
Change in Level of IGFBP2, IGFBP3 and Growth Hormone GH	66 pg/mL Standard Deviation 159.9	-25 pg/mL Standard Deviation 327.8	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Arm I (Androgen Deprivation and Cixutumumab) n=18 Participants 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	Arm II (Androgen Deprivation Therapy) n=9 Participants 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	PSA Non-Responders 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)
Change in Level of Insulin	0 ulU/mL Standard Deviation 5.1	0 ulU/mL Standard Deviation 1.5	—

Adverse Events

Arm I (Androgen Deprivation and Cixutumumab)

Serious events: 10 serious events

Other events: 101 other events

Deaths: 0 deaths

Arm II (Androgen Deprivation Therapy)

Serious events: 4 serious events

Other events: 94 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Evan Y. Yu, MD

Department of Medicine, Division of Oncology, University of Washington

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Arm I (Androgen Deprivation and Cixutumumab) n=101 participants at risk 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	Arm II (Androgen Deprivation Therapy) n=104 participants at risk 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
Blood and lymphatic system disorders Anemia	0.99% 1/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Cardiac disorders Left ventricular systolic dysfunction	0.99% 1/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Colonic obstruction	0.99% 1/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Dry mouth	0.99% 1/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Duodenal ulcer	0.99% 1/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Dysphagia	0.99% 1/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Gastric hemorrhage	0.99% 1/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Mucositis oral	0.99% 1/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Nausea	0.99% 1/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Vomiting	2.0% 2/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
General disorders Death NOS	0.00% 0/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	1.9% 2/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
General disorders Malaise	0.99% 1/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
General disorders Pain	0.99% 1/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Infections and infestations Soft tissue infection	0.99% 1/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Infections and infestations Tooth infection	0.99% 1/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Infections and infestations Urinary tract infection	0.99% 1/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Injury, poisoning and procedural complications Fracture	0.99% 1/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Metabolism and nutrition disorders Hypercalcemia	0.99% 1/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Metabolism and nutrition disorders Hyperglycemia	0.99% 1/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Metabolism and nutrition disorders Hypocalcemia	0.99% 1/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Musculoskeletal and connective tissue disorders Exostosis	0.99% 1/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Nervous system disorders Cognitive disturbance	0.99% 1/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Nervous system disorders Stroke	0.00% 0/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.96% 1/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Renal and urinary disorders Urinary tract obstruction	0.99% 1/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.96% 1/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Vascular disorders Thromboembolic event	0.99% 1/101 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/104 • Up to 28 weeks Participants were monitored for toxicity prior to each cycle or at more frequent intervals appropriate for that participant, as judged by the treating physician.