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
Overview
- Phase
- Phase 2
- Intervention
- Bicalutamide
- Conditions
- Prostate Adenocarcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 211
- Locations
- 170
- Primary Endpoint
- Undetectable PSA Rate
- Status
- Completed
- Last Updated
- 8 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Exclusion Criteria
- Not provided
Arms & Interventions
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.
Intervention: Bicalutamide
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.
Intervention: Cixutumumab
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.
Intervention: Goserelin Acetate
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.
Intervention: Laboratory Biomarker Analysis
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.
Intervention: Leuprolide Acetate
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.
Intervention: Pharmacological Study
Arm II (androgen deprivation therapy)
Patients receive androgen deprivation therapy comprising bicalutamide and either goserelin acetate or leuprolide acetate as in arm I.
Intervention: Bicalutamide
Arm II (androgen deprivation therapy)
Patients receive androgen deprivation therapy comprising bicalutamide and either goserelin acetate or leuprolide acetate as in arm I.
Intervention: Goserelin Acetate
Arm II (androgen deprivation therapy)
Patients receive androgen deprivation therapy comprising bicalutamide and either goserelin acetate or leuprolide acetate as in arm I.
Intervention: Laboratory Biomarker Analysis
Arm II (androgen deprivation therapy)
Patients receive androgen deprivation therapy comprising bicalutamide and either goserelin acetate or leuprolide acetate as in arm I.
Intervention: Leuprolide Acetate
Arm II (androgen deprivation therapy)
Patients receive androgen deprivation therapy comprising bicalutamide and either goserelin acetate or leuprolide acetate as in arm I.
Intervention: Pharmacological Study
Outcomes
Primary Outcomes
Undetectable PSA Rate
Time Frame: 7 months
Undetectable PSA rate (\<= 0.2 ng/mL) after seven cycles (28 weeks) of protocol treatment
Secondary Outcomes
- Toxicity(Up to 28 weeks)
- Proportion of Patients Who do Not Achieve a Partial PSA Response(Up to 5 years)
- Accuracy of the Prognostic Model of Undetectable PSA (Developed From SWOG-9346)(Up to 5 years)
- Correlation of microRNA Measures With 28-week PSA Response(Baseline to 28 weeks)
- Correlation of microRNA Measures With Baseline Circulating Tumor Cell (CTC) Counts(Baseline)
- Change in Level of CTCs(Baseline to 28 weeks)