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

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the prostate

  • Metastatic disease as evidenced by soft tissue and/or bony metastases, including ≥ 1 of the following:

    • 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)

• Patients with measurable disease must have radiographic assessment (at least an abdominal/pelvic CT scan) within the past 28 days

  • Patients with non-measurable disease must be assessed (e.g., bone scan) within the past 42 days
• PSA ≥ 5 ng/mL within 90 days before initiation of androgen-deprivation therapy

• No known brain metastases

  • Brain imaging studies not required for patients with no neurologic signs or symptoms

• Zubrod performance status (PS) 0-2

  • Zubrod PS 3 allowed if due to bone pain
• WBC ≥ 3,000/mm^3
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 3 times ULN (≤ 5 times ULN for liver metastases)
• Creatinine ≤ 2.0 times ULN OR creatinine clearance ≥ 40 mL/min
• INR ≤ 1.5
• PTT ≤ 5 seconds above the ULN

• Hemoglobin A1c (HgA1C) ≤ 7 AND fasting glucose < 160 mg/dL or below ULN

  • Patients with diabetes mellitus who meet this criterion are eligible provided they are on a stable dietary or therapeutic regimen
• Fertile patients must use effective contraception during and for ≥ 3 months after completion of study therapy

• No known LVEF ≥ 10% below the lower limit of normal

  • Patients with suspected LV dysfunction not confirmed by review of medical history must undergo MUGA or ECHO within 90 days before study entry
• No history of symptomatic congestive heart failure
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to cixutumumab
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or stage I or II cancer currently in complete remission

• Prior medical castration allowed provided it was initiated within the past 30 days

  • Patients on a luteinizing hormone-releasing hormone (LHRH) agonist (e.g., leuprolide acetate or goserelin) must be willing to continue the LHRH agonist in addition to bicalutamide during study treatment
  • Patients on a different anti-androgen (e.g., flutamide) must be willing change to bicalutamide during study treatment
• Prior bilateral orchiectomy allowed provided it was performed within the past 30 days
• At least 28 days since prior non-orchiectomy surgery and recovered
• More than 28 days since prior strontium-89, rhenium-186, rhenium-188, or samarium-153 radionuclide therapy
• At least 28 days since prior radiotherapy or biologic therapy (e.g., vaccines, immunotherapy, anti-sense agents, small molecules, or monoclonal antibodies) and recovered
• No prior cytotoxic chemotherapy for metastatic prostate cancer
• No prior treatment with agents that directly inhibit IGF or IGFR
• No prior chimerized or murine monoclonal antibody therapy
• No concurrent antiretroviral therapy for HIV-positive patients

• No concurrent treatment with any of the following:

  • Chemotherapy
  • Hormonal therapy (other than the LHRH agonist and oral anti-androgen)
  • Radiotherapy
  • Immunotherapy
  • Any other anticancer therapy
  • 5-alpha reductase inhibitors (e.g., finasteride or dutasteride)
  • Ketoconazole
  • Diethylstilbestrol/DES
  • Other estrogen-based therapy

• Concurrent prophylactic low-dose coumadin or low-molecular weight heparin allowed provided coagulation criteria are met

  • Patients requiring full-dose (therapeutic) anticoagulation are eligible provided they are on a stable dose of anticoagulation AND the coagulation parameters are stable within the therapeutic range (e.g., INR 2-3 for patients on therapeutic warfarin)