Androgen Deprivation Therapy +/- Radium-223 Dichloride in Metastatic Prostate Cancer With Bone Metastases
Condition: Prostate Cancer; Bone Metastases; Prostate Neoplasms
MeSH terms: Prostatic Neoplasms; Neoplasm Metastasis; Bone Neoplasms; Bone Marrow Diseases
Intervention: LHRH agonist/antagonist; Bicalutamide; Radium-223 dichloride
Intervention description: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle.; Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle.; Radium-223 dichloride, 50 kBq (1.35 microcurie) per kg body weight intravenous (IV bolus) every 28 days for 6 injections
Intervention MeSH terms: Bicalutamide; Radium Ra 223 dichloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Androgen Deprivation Therapy; Androgen Receptor Antagonist; Radium-223 Dichloride; Placebo

Summary:

      Newly diagnosed metastatic prostate cancer subjects with bone metastases will be accrued to
      this stratified randomized 2-arm Phase II trial. Subjects will be randomized 1:2 to ADT or
      ADT with Radium-223 dichloride respectively.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All subjects or their legally authorized representative must be informed of the
             investigational nature of the study and provide written informed consent and HIPAA
             authorization for release of personal health information before performance of any
             study related procedure not part of routine medical care. NOTE: HIPAA authorization
             may be included in the informed consent or obtained separately.

          -  Men ≥ 18 years of age at the time of informed consent.

          -  Histological or cytological evidence of prostate adenocarcinoma.

          -  All subjects must have radiologic or pathologic evidence of ≥ 2 skeletal lesions with
             or without pain at baseline on bone scan or axial imaging or 1 skeletal lesion and
             bone pain within 28 days prior to the registration.

          -  All subjects must have a radiographic assessment (chest or abdominal/pelvic CT or MRI)
             within 28 days prior to registration but do not need to have measurable disease.

          -  ECOG (Eastern Cooperative Oncology Group) Performance Status of 0-2 within 28 days
             prior to registration. ECOG Performance Status of 3 will only be allowed if judged by
             the treating investigator as attributable exclusively to bone pain.

          -  Subjects must fall into one of the two populations below:

          -  EARLY INDUCTION GROUP: Subjects who have started androgen deprivation therapy
             (luteinizing hormone-releasing hormone (LHRH) agonist or antagonist therapy with or
             without an anti-androgen agent) a maximum of 28 days before registration and who
             otherwise meet all the eligibility criteria.

          -  LATE INDUCTION GROUP: Subjects who have NOT started any androgen deprivation therapy
             (luteinizing hormone-releasing hormone (LHRH) agonist or antagonist therapy with or
             without an antiandrogen agent).

          -  Anti-androgen receptor antagonist therapy must be bicalutamide. Subjects already
             started on other anti-androgens must be willing to switch over to bicalutamide.

          -  Any prior androgen-deprivation therapy or finasteride as neoadjuvant or adjuvant
             therapy or for biochemical recurrence must have been discontinued at least 6 months
             prior to registration.

          -  Prior surgical treatment for prostate cancer is allowed but must have been completed
             at least 14 days prior to registration and any toxicity from such therapy must have
             recovered to ≤ grade 1 per CTCAE version 4 criteria by the time of registration.

          -  All subjects, including those who are surgically sterilized, must be willing to use an
             effective method of contraception (barrier method of birth control or abstinence) from
             the time informed consent is signed until 6 months after completion of protocol
             therapy.

          -  Subjects must consent to bank whole blood, serum, plasma for future unspecified
             studies.

        Exclusion Criteria:

          -  Prior cytotoxic chemotherapy for metastatic prostate cancer. Prior cytotoxic
             chemotherapy with curative intent in the neoadjuvant or adjuvant setting is allowed
             but must have been completed at least 6 months prior to registration. No cytotoxic
             chemotherapy is allowed during protocol specified therapy.

          -  Prior concomitant therapy with ketoconazole, aminoglutethimide or abiraterone acetate
             or enzalutamide (MDV3100) or intent to treat with the above. Concurrent megestrol for
             hot flashes is allowed.

          -  Prior or ongoing bisphosphonate (e.g,. zoledronic acid) or RANKL inhibitor (e.g.
             denosumab) use is NOT allowed except when used solely for osteoporosis and strictly
             per guidelines for that indication. Bisphosphonate or RANKL inhibitor cannot be
             initiated for any indication during protocol specified therapy without consent of the
             sponsor-investigator of the study.

          -  Prior systemic radiotherapy with strontium-89, samarium-153, rhenium-186 or
             rhenium-188.

          -  Diagnosis of aplastic anemia, pure red cell aplasia, myelodysplasia or any of the
             other bone marrow failure states.

          -  Any neuroendocrine differentiation including small cell carcinoma on histology or
             cytology.

          -  No prior malignancy except for non-melanomatous skin cancer or non-muscle invasive
             bladder cancer or adequately treated Stage I or II cancer (adequacy at discretion of
             treating investigator) from which the subject is currently in complete remission, or
             any other cancer from which the subject has been disease-free for at least 3 years.

          -  History of or active CNS metastasis (brain, leptomeningeal or cord compression). Brain
             imaging studies are not required for eligibility if the subject has no neurologic
             signs or symptoms suggestive of brain metastasis. Subjects with neurological symptoms
             are recommended to undergo a head CT scan (with or without intravenous contrast) or
             brain MRI (with or without intravenous contrast) to exclude brain metastasis. If brain
             imaging studies are performed, they must be negative for CNS disease. Skull bone
             involvement without neurological impact by prostate cancer is allowed.

          -  Treatment with any other investigational agent within 28 days prior to registration.
             Subjects must not be treated with any other investigational agent while on protocol
             specified therapy.

          -  Prior hemibody external radiation. Any external radiation therapy must have been
             completed at least 14 days prior to registration. Any toxicity from such therapy must
             have recovered to ≤ grade 1 per CTCAE version 4 criteria by the time of registration.

          -  Clinically significant infections as judged by the treating investigator. Subjects
             must not have been diagnosed with human immunodeficiency virus (HIV) infection, active
             chronic hepatitis B or C, life-threatening illness unrelated to cancer, or any serious
             medical or psychiatric illness that could, in the investigator's opinion, potentially
             interfere with participation in this study. Subjects should be tested for hepatitis B
             or C or HIV infection during screening only if they are considered by the investigator
             to be at high risk for these infections.

          -  Known hypersensitivity to bicalutamide.

          -  Known gastrointestinal (GI) disease or procedure that could interfere with the GI
             absorption or tolerance of bicalutamide, including difficulty swallowing oral
             medications.

          -  Grade III/IV cardiac disease as defined by the New York Heart Association Criteria
             (i.e., subjects with cardiac disease resulting in marked limitation of physical
             activity or resulting in inability to carry on any physical activity without
             discomfort), symptomatic pulmonary embolism within 3 months, unstable angina pectoris,
             myocardial infarction within 6 months, or serious uncontrolled cardiac arrhythmia as
             determined by the treating physician.