Clinical trial NCT01120236
Conditions: Prostate Adenocarcinoma Recurrent Prostate Carcinoma Stage IV Prostate Cancer
Sponsor: National Cancer Institute (NCI)
Start date: 2010-12-01; Completion date: 2017-08-23
Enrollment: 211 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Detailed description:
PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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

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

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

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

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

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

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

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

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

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

Arms: arm 1: 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. arm 2: Patients receive androgen deprivation therapy comprising bicalutamide and either goserelin acetate or leuprolide acetate as in arm I.
Interventions: intervention 1: Bicalutamide intervention 2: Cixutumumab intervention 3: Goserelin Acetate intervention 4: Laboratory Biomarker Analysis intervention 5: Leuprolide Acetate intervention 6: Pharmacological Study
Intervention descriptions: intervention 1: Given PO intervention 2: Given IV intervention 3: Given SC intervention 4: Correlative studies intervention 5: Given IM intervention 6: Correlative studies

Protocol documents: