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.
PRIMARY OBJECTIVES: I. To compare the undetectable prostate-specific antigen (PSA) rate (PSA \< 0.2 ng/mL) after seven cycles (28 weeks) of protocol treatment between those randomized to a luteinizing hormone-releasing hormone (LHRH) agonist and bicalutamide and those randomized to a LHRH agonist, bicalutamide and IMC-A12 (cixutumumab). SECONDARY OBJECTIVES: I. To assess the safety and tolerability of the combination of IMC-A12 with a LHRH agonist and bicalutamide. II. To compare the proportion of men who do not achieve a PSA of \< 4 ng/mL between the two groups. III. To assess the accuracy of the prognostic model of undetectable PSA that was developed from Southwest Oncology Group (SWOG)-9346 using current trial data from each arm. IV. To assess serum samples and peripheral blood mononuclear cells (PBMNC) for pharmacodynamic activity with potential biomarkers for IMC-A12 (including, but not limited to: insulin-like growth factor \[IGF\]-I, free IGF-I, IGF-II, IGF binding protein \[IGFBP\]2, IGFBP3, growth hormone, insulin and C-peptide) obtained from optional blood specimens both before initiation of androgen deprivation therapy and twelve weeks after initiation of combined therapy. V. To determine baseline pre-treatment circulating tumor cell (CTC) quantities and response to therapy (for those patients with detectable CTC levels \>= 1) twelve weeks later. VI. In the same subset of patients where CTC levels are obtained, determine baseline serum levels of micro-ribonucleic acids (RNAs) to include but not limited to microRNA (mi)-141 both before initiation of androgen deprivation therapy and twelve weeks after combined therapy. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive androgen deprivation therapy comprising bicalutamide orally (PO) once daily (QD) on days 1-28 and either goserelin acetate subcutaneously (SC) or leuprolide acetate intramuscularly (IM) every 1, 3, 4, 6, or 12 months. Patients also receive cixutumumab intravenously (IV) over 1 hour on days 1 and 15. Treatment repeats every 28 days for 7 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive androgen deprivation therapy comprising bicalutamide and either goserelin acetate or leuprolide acetate as in arm I. After completion of study treatment, patients are followed up every 6 months for 2 years and then annually for 3 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
211
Given PO
Given IV
Given SC
Correlative studies
Given IM
Correlative studies
Fairbanks Memorial Hospital
Fairbanks, Alaska, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Highlands Oncology Group-Rogers
Rogers, Arkansas, United States
City of Hope Comprehensive Cancer Center
Duarte, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
Undetectable PSA Rate
Undetectable PSA rate (\<= 0.2 ng/mL) after seven cycles (28 weeks) of protocol treatment
Time frame: 7 months
Toxicity
Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time frame: Up to 28 weeks
Proportion of Patients Who do Not Achieve a Partial PSA Response
A partial PSA response is considered \<= 4 ng/mL
Time frame: Up to 5 years
Accuracy of the Prognostic Model of Undetectable PSA (Developed From SWOG-9346)
The logistic regression algorithm for predicting undetectable PSA that was developed for SWOG-9346 using its baseline risk factors (age at registration, performance status, baseline PSA, and bone pain) will be applied to each arm of this trial to evaluate the level of agreement between the observed and predicted undetectable PSA rates.
Time frame: Up to 5 years
Correlation of microRNA Measures With 28-week PSA Response
The Friedman test will be used to evaluate correlations between microRNA measures (CT) and 28-week PSA response.
Time frame: Baseline to 28 weeks
Correlation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) Counts
The Friedman test will be used to evaluate correlations between microRNA measures (CT) and Baseline CTCs.
Time frame: Baseline
Change in Level of CTCs
Will be correlated with 28-week PSA response.
Time frame: Baseline to 28 weeks
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Cedars-Sinai Medical Center
Los Angeles, California, United States
Fremont - Rideout Cancer Center
Marysville, California, United States
Valley Medical Oncology Consultants
Pleasanton, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
Tahoe Forest Cancer Center
Truckee, California, United States
...and 160 more locations