Bicalutamide and Goserelin or Leuprolide Acetate With or Without Cixutumumab in Treating Patients With Newly Diagnosed Metastatic Prostate Cancer
Condition: Prostate Adenocarcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Bicalutamide; Cixutumumab; Goserelin Acetate; Laboratory Biomarker Analysis; Leuprolide Acetate; Pharmacological Study
Intervention description: Given PO; Given IV; Given SC; Correlative studies; Given IM; Correlative studies
Intervention MeSH terms: Leuprolide; Goserelin; Bicalutamide; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 211.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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

          -  Patients must not have received prior strontium-89, rhenium-186, rhenium-188, or
             samarium-153 radionuclide therapy within 28 days prior to registration

          -  Patients may have received prior radiation therapy or biologic therapy (e.g. vaccines,
             immunotherapy, anti-sense, small molecules, monoclonal antibodies); however, at least
             28 days must have elapsed since completion of therapy and patient must have recovered
             from all side effects

          -  Patients may have received prior surgery; for all major surgeries, at least 28 days
             must have elapsed since completion and patient must have recovered from all side
             effects

          -  Leukocytes >= 3,000 mcL

          -  Absolute neutrophil count (ANC) >= 1,500 mcL

          -  Hemoglobin >= 9 g/dL

          -  Platelets >= 100,000/mcL

          -  Bilirubin =< 1.5 times the institutional upper limit of normal (ULN) (unless
             documented Gilbert's disease)

          -  Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
             serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3
             times the institutional ULN, or =< 5 times the institutional ULN if liver metastases
             are present

          -  Creatinine =< 2.0 x the institutional ULN or calculated creatinine clearance >= 40
             mL/min

          -  International normalized ratio (INR) =< 1.5

          -  Partial thromboplastin time (PTT) no more than 5 seconds above the institutional ULN

          -  Patients receiving prophylactic low dose coumadin or low molecular weight heparin are
             eligible as long as they meet these coagulation criteria; patients requiring full-dose
             (therapeutic) anticoagulation are eligible provided that they have been 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)

          -  Patients must have a hemoglobin A1c (HgA1c) =< 7% AND fasting glucose of < 160 mg/dL
             or below the institutional ULN within 14 days prior to registration; patients with
             diabetes mellitus who meet this criterion must be on a stable dietary or therapeutic
             regimen for this condition

          -  Patients must not have a history of symptomatic congestive heart failure or a known
             ejection fraction (left ventricular ejection fraction [LVEF]) that is >= 10% below the
             lower limit of normal (LLN); if left ventricular (LV) dysfunction is suspected, but
             not confirmed by review of past medical history, a multi gated acquisition scan (MUGA)
             or echocardiogram must be obtained within 90 days prior to registration

          -  Patient must not have a history of allergic reaction attributed to compounds of
             similar chemical or biologic composition to IMC-A12; patients must not have received
             prior chimerized or murine monoclonal antibody therapy

          -  Patients must have a Zubrod performance status of 0 - 2; Zubrod performance status 3
             will be allowed if from bone pain only

          -  Patients with human immunodeficiency virus (HIV) positivity requiring antiretroviral
             therapy are not eligible for this study

          -  Patients must have no plans to receive concurrent chemotherapy, hormonal therapy
             (other than the LHRH agonist and oral anti-androgen), radiotherapy, immunotherapy or
             any other type of therapy for treatment of cancer while on this protocol treatment;
             concurrent bone targeting agents that do not have effect on PSA (i.e. denosumab or
             zoledronic acid) are allowed

          -  Patients must have no plans to receive concurrent five-alpha reductase inhibitors
             (e.g. finasteride and dutasteride), ketoconazole, diethylstilbestrol/DES, or other
             estrogen-based therapy while on this protocol treatment

          -  No other prior malignancy is allowed except for the following: adequately treated
             basal cell or squamous cell skin cancer, adequately treated stage I or II cancer from
             which the patient is currently in complete remission, or any other cancer from which
             the patient has been disease-free for 5 years

          -  Men of reproductive potential must have agreed to use an effective contraceptive
             method while receiving treatment on this study and for at least three months after
             protocol treatment ends

          -  All patients must be informed of the investigational nature of this study and must
             sign and give written informed consent in accordance with institutional and federal
             guidelines

          -  As part of the OPEN registration process, the treating institution's identity is
             provided in order to ensure that the current (within 365 days) date of institutional
             review board approval for this study has been entered in the system