Androgen Deprivation Therapy +/- Radium-223 Dichloride in... | NCT02582749

Name	Class
Hoosier Cancer Research Network	OTHER
Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma	INDUSTRY

Description Module

Detailed Description

OUTLINE: This is a multi-center, randomized trial.

STRATIFICATION FACTORS:

Subjects will be stratified based on serum total alkaline phosphatase at baseline and extent of disease (described below). Randomization will occur within stratification group.

Extent of Disease: <6 skeletal metastases with no visceral metastases versus ≥6 skeletal metastases or visceral metastases.
Serum total alkaline phosphatase at baseline: normal vs abnormal. Abnormal alkaline phosphatase is defined as > 130 IU/L.

Early Induction or Late Induction status will not be a stratification criterion.

TREATMENT SCHEDULE: CONTROL ARM A

All subjects will receive androgen deprivation therapy with a LHRH agonist (any LHRH agonist such as leuprolide acetate or goserelin acetate is acceptable) or a LHRH antagonist (degarelix) or bilateral orchiectomy, with dosage determined by the treating physician. Route of administration and cycle days will be administered as per package insert. Androgen deprivation therapy with LHRH agonist or LHRH antagonist will be given continuously.

All subjects will receive bicalutamide, 50 mg Oral (PO) Daily

TREATMENT SCHEDULE: EXPERIMENTAL ARM B

All subjects will receive bicalutamide, 50 mg oral (PO) daily

All subjects will receive Radium-223 dichloride, 50 kBq (1.35 microcurie) per kg body weight, intravenous (IV bolus) every 28 days for 6 injections

The following laboratory values must be obtained within 28 days prior to registration for protocol therapy:

Hematopoietic:

Hemoglobin (Hgb) ≥ 8.0 g/dL (80 g/L) without packed RBC transfusion
Platelets ≥ 100 K/mm3
Absolute neutrophil count (ANC) ≥ 1.5 K/mm3

Hepatic:

Total Bilirubin ≤ 2 x institutional upper limit of normal (ULN) except subjects with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL
Aspartate aminotransferase (AST, SGOT) ≤ 2.5 x institutional ULN (≤ 5 x institutional ULN in the presence of liver metastases).
Alanine aminotransferase (ALT, SGPT) ≤ 2.5 x institutional ULN (≤ 5 × institutional ULN in the presence of liver metastases).

Renal:

Estimated Creatinine Clearance by Cockcroft-Gault formula ≥ 30 mL/min

Label	Type	Description	Intervention Names
Control Arm A	Active Comparator	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days.	Drug: LHRH agonist/antagonist Drug: Bicalutamide
Experimental Arm B	Experimental	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. Radium-223 dichloride, 50 kBq/kg body weight, will be administered as a bolus intravenous (IV) injection at intervals of every 28 days for up to 6 cycles.	Drug: LHRH agonist/antagonist Drug: Bicalutamide Radiation: Radium-223 dichloride

Name	Type	Description	Arm Group Labels	Other Names
LHRH agonist/antagonist	Drug	Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle.	Control Arm A

Measure	Description	Time Frame
Radiological Progression-Free Survival (rPFS)	rPFS assessed using Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) to compare outcomes of subjects on experimental arm vs control arm	From date of randomization to disease progression or death from any cause, up to a maximum of 24 months.

Measure	Description	Time Frame
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug, Graded According to NCI Common Terminology Criteria for Adverse Events v 4.0 (CTCAE)	The intensity of AEs for subjects on both arms graded according to CTCAE v4.0 on a five-point scale (Grade 1 to 5: Mild, Moderate, Severe, Life-threatening and Death)	From date of first dose until 30 days after the last treatment, assessed for a maximum of 24 months

Eligibility Module

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.

Name	Affiliation	Role
Ajjai Alva, M.D.	Hoosier Cancer Research Network	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
University of Arizona Cancer Center at Dignity Health St. Joseph's		Phoenix	Arizona	85004	United States

ID	Title	Description
FG000	Control Arm A	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jan 9, 2017

ID	Title	Description
BG000	Control Arm A	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle.
BG001	Experimental Arm B	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. Radium-223 dichloride, 50 kBq/kg body weight, will be administered as a bolus intravenous (IV) injection at intervals of every 28 days for up to 6 cycles. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle. Radium-223 dichloride: Radium-223 dichloride, 50 kBq (1.35 microcurie) per kg body weight intravenous (IV bolus) every 28 days for 6 injections
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG0005 BG00111 BG00216

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Radiological Progression-Free Survival (rPFS)

rPFS assessed using Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) to compare outcomes of subjects on experimental arm vs control arm

Data was not collected or analyzed for this objective due to the termination of the study by the funder

Posted

From date of randomization to disease progression or death from any cause, up to a maximum of 24 months.

ID	Title	Description
OG000	Control Arm A	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle.
OG001	Experimental Arm B	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. Radium-223 dichloride, 50 kBq/kg body weight, will be administered as a bolus intravenous (IV) injection at intervals of every 28 days for up to 6 cycles. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle. Radium-223 dichloride: Radium-223 dichloride, 50 kBq (1.35 microcurie) per kg body weight intravenous (IV bolus) every 28 days for 6 injections

Units	Counts
Participants	OG0000 OG0010

Secondary

Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug, Graded According to NCI Common Terminology Criteria for Adverse Events v 4.0 (CTCAE)

The intensity of AEs for subjects on both arms graded according to CTCAE v4.0 on a five-point scale (Grade 1 to 5: Mild, Moderate, Severe, Life-threatening and Death)

Data was not collected or analyzed for this objective due to the termination of the study by the funder

Posted

From date of first dose until 30 days after the last treatment, assessed for a maximum of 24 months

ID	Title	Description
OG000	Control Arm A	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle.
OG001	Experimental Arm B	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. Radium-223 dichloride, 50 kBq/kg body weight, will be administered as a bolus intravenous (IV) injection at intervals of every 28 days for up to 6 cycles. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle. Radium-223 dichloride: Radium-223 dichloride, 50 kBq (1.35 microcurie) per kg body weight intravenous (IV bolus) every 28 days for 6 injections

Secondary

Time to First Skeletal-Related Event (SRE)

SRE of subjects on both arms assessed by bone scan or axial imaging

Data was not collected or analyzed for this objective due to the termination of the study by the funder

Posted

From date of first dose until 30 days after the last treatment, assessed for a maximum of 24 months

ID	Title	Description
OG000	Control Arm A	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle.
OG001	Experimental Arm B	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. Radium-223 dichloride, 50 kBq/kg body weight, will be administered as a bolus intravenous (IV) injection at intervals of every 28 days for up to 6 cycles. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle. Radium-223 dichloride: Radium-223 dichloride, 50 kBq (1.35 microcurie) per kg body weight intravenous (IV bolus) every 28 days for 6 injections

Secondary

Secondary Neoplasms

Secondary neoplasms of subjects on both arms assessed by bone scan or axial imaging

Data was not collected or analyzed for this objective due to the termination of the study by the funder

Posted

From date of first dose until 30 days after the last treatment, assessed for a maximum of 24 months

ID	Title	Description
OG000	Control Arm A	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle.
OG001	Experimental Arm B	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. Radium-223 dichloride, 50 kBq/kg body weight, will be administered as a bolus intravenous (IV) injection at intervals of every 28 days for up to 6 cycles. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle. Radium-223 dichloride: Radium-223 dichloride, 50 kBq (1.35 microcurie) per kg body weight intravenous (IV bolus) every 28 days for 6 injections

Secondary

PSA Complete Response Rates

Subjects on both arms with PSA ≤ 0.2 ng/mL after 7 months of androgen deprivation therapy

Data was not collected or analyzed for this objective due to the termination of the study by the funder

Posted

From date of first dose of androgen deprivation therapy (ADT) until completion of 7 cycles (28 weeks)

ID	Title	Description
OG000	Control Arm A	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle.
OG001	Experimental Arm B	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. Radium-223 dichloride, 50 kBq/kg body weight, will be administered as a bolus intravenous (IV) injection at intervals of every 28 days for up to 6 cycles. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle. Radium-223 dichloride: Radium-223 dichloride, 50 kBq (1.35 microcurie) per kg body weight intravenous (IV bolus) every 28 days for 6 injections

Secondary

PSA Partial Response Rates

Subjects on both arms with PSA between 0.2 and ≤ 4 ng/mL after 7 months of androgen deprivation therapy.

Data was not collected or analyzed for this objective due to the termination of the study by the funder

Posted

From date of first dose of ADT until completion of 7 cycles (28 weeks)

ID	Title	Description
OG000	Control Arm A	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle.
OG001	Experimental Arm B	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. Radium-223 dichloride, 50 kBq/kg body weight, will be administered as a bolus intravenous (IV) injection at intervals of every 28 days for up to 6 cycles. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle. Radium-223 dichloride: Radium-223 dichloride, 50 kBq (1.35 microcurie) per kg body weight intravenous (IV bolus) every 28 days for 6 injections

Secondary

Median Time to Castration Resistance

Castration resistance for subjects on both arms determined by first PSA level increase and/or radiographic progression by first imaging assessment showing progression

Data was not collected or analyzed for this objective due to the termination of the study by the funder

Posted

From date of ADT (first LHRH agonist/antagonist/surgical castration) to date of PSA and/or radiographic progression, assessed for a maximum of 24 months

ID	Title	Description
OG000	Control Arm A	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle.
OG001	Experimental Arm B	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. Radium-223 dichloride, 50 kBq/kg body weight, will be administered as a bolus intravenous (IV) injection at intervals of every 28 days for up to 6 cycles. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle. Radium-223 dichloride: Radium-223 dichloride, 50 kBq (1.35 microcurie) per kg body weight intravenous (IV bolus) every 28 days for 6 injections

Secondary

2-Year PSA Progression Free Survival (PFS)

PSA PFS for subjects on both arms defined as first PSA level increase

Data was not collected or analyzed for this objective due to the termination of the study by the funder

Posted

From date of randomization to first occurrence of PSA progression, symptomatic deterioration, or death due to any cause, assessed up to 24 months

ID	Title	Description
OG000	Control Arm A	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle.
OG001	Experimental Arm B	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. Radium-223 dichloride, 50 kBq/kg body weight, will be administered as a bolus intravenous (IV) injection at intervals of every 28 days for up to 6 cycles. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle. Radium-223 dichloride: Radium-223 dichloride, 50 kBq (1.35 microcurie) per kg body weight intravenous (IV bolus) every 28 days for 6 injections

Secondary

2-Year Overall Survival (OS)

OS for subjects on both arms

Data was not collected or analyzed for this objective due to the termination of the study by the funder

Posted

From date of randomization to death from any cause, assessed up to 24 months

ID	Title	Description
OG000	Control Arm A	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle.
OG001	Experimental Arm B	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. Radium-223 dichloride, 50 kBq/kg body weight, will be administered as a bolus intravenous (IV) injection at intervals of every 28 days for up to 6 cycles. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle. Radium-223 dichloride: Radium-223 dichloride, 50 kBq (1.35 microcurie) per kg body weight intravenous (IV bolus) every 28 days for 6 injections

Secondary

12-Week Alkaline Phosphatase (ALP) Normalization

ALP normalization for subjects with abnormal ALP at randomization

Data was not collected or analyzed for this objective due to the termination of the study by the funder

Posted

From date of randomization until completion of 12 weeks of therapy

ID	Title	Description
OG000	Control Arm A	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle.
OG001	Experimental Arm B	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. Radium-223 dichloride, 50 kBq/kg body weight, will be administered as a bolus intravenous (IV) injection at intervals of every 28 days for up to 6 cycles. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle. Radium-223 dichloride: Radium-223 dichloride, 50 kBq (1.35 microcurie) per kg body weight intravenous (IV bolus) every 28 days for 6 injections

Secondary

Time to ALP Progression

ALP progression of 25% or greater from baseline/nadir for subjects on both arms

Data was not collected or analyzed for this objective due to the termination of the study by the funder

Posted

From date of randomization until date of ALP progression, assessed up to 24 months

ID	Title	Description
OG000	Control Arm A	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle.
OG001	Experimental Arm B	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. Radium-223 dichloride, 50 kBq/kg body weight, will be administered as a bolus intravenous (IV) injection at intervals of every 28 days for up to 6 cycles. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle. Radium-223 dichloride: Radium-223 dichloride, 50 kBq (1.35 microcurie) per kg body weight intravenous (IV bolus) every 28 days for 6 injections

Secondary

Change in Pain Over Time

Subjects on both arms self-reported evaluation of worst pain item, as well as the subscale scores for pain severity and pain interference as determined by subject responses on the BPI-SF questionnaire.

Data was not collected or analyzed for this objective due to the termination of the study by the funder

Posted

From baseline until 30 days after the last treatment, assessed for a maximum of 24 months

ID	Title	Description
OG000	Control Arm A	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle.
OG001	Experimental Arm B	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. Radium-223 dichloride, 50 kBq/kg body weight, will be administered as a bolus intravenous (IV) injection at intervals of every 28 days for up to 6 cycles. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle. Radium-223 dichloride: Radium-223 dichloride, 50 kBq (1.35 microcurie) per kg body weight intravenous (IV bolus) every 28 days for 6 injections

Secondary

Analgesic Use by WHO Ladder Score

Analgesic use scores for subjects on both arms will be assigned by the treating physician based on the subject's daily analgesic use on average. A single numeric score (0, 1, 2 or 3) will be assigned based on the 3-step WHO pain ladder.

Data was not collected or analyzed for this objective due to the termination of the study by the funder

Posted

From baseline until 30 days after the last treatment, assessed for a maximum of 24 months

ID	Title	Description
OG000	Control Arm A	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle.
OG001	Experimental Arm B	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. Radium-223 dichloride, 50 kBq/kg body weight, will be administered as a bolus intravenous (IV) injection at intervals of every 28 days for up to 6 cycles. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle. Radium-223 dichloride: Radium-223 dichloride, 50 kBq (1.35 microcurie) per kg body weight intravenous (IV bolus) every 28 days for 6 injections

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
ABDOMINAL PAIN	Gastrointestinal disorders	CTCAEv4	Non-systematic Assessment	EG0002 events1 affected5 at risk EG0012 events2 affected11 at risk
ALKALINE PHOSPHATASE INCREASED	Investigations	CTCAEv4	Non-systematic Assessment	EG0002 events1 affected5 at risk EG0012 events2 affected11 at risk
ANEMIA	Blood and lymphatic system disorders	CTCAEv4	Non-systematic Assessment	EG0002 events2 affected5 at risk EG0018 events5 affected11 at risk
ARTHRALGIA	Musculoskeletal and connective tissue disorders	CTCAEv4	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected11 at risk
BACK PAIN	Musculoskeletal and connective tissue disorders	CTCAEv4	Non-systematic Assessment	EG0002 events2 affected5 at risk EG0014 events3 affected11 at risk
BLOOD AND LYMPHATIC SYSTEM DISORDERS - OTHER, SPECIFY	Blood and lymphatic system disorders	CTCAEv4	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0011 events1 affected11 at risk
CONSTIPATION	Gastrointestinal disorders	CTCAEv4	Non-systematic Assessment	EG0004 events3 affected5 at risk EG0014 events4 affected11 at risk
DEPRESSION	Psychiatric disorders	CTCAEv4	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0011 events1 affected11 at risk
DYSPNEA	Respiratory, thoracic and mediastinal disorders	CTCAEv4	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0012 events2 affected11 at risk
ERECTILE DYSFUNCTION	Reproductive system and breast disorders	CTCAEv4	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0011 events1 affected11 at risk
FALL	Injury, poisoning and procedural complications	CTCAEv4	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected11 at risk
FATIGUE	General disorders	CTCAEv4	Non-systematic Assessment	EG0001 events1 affected5 at risk EG00112 events7 affected11 at risk
GASTROESOPHAGEAL REFLUX DISEASE	Gastrointestinal disorders	CTCAEv4	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0011 events1 affected11 at risk
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - OTHER, SPECIFY	General disorders	CTCAEv4	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected11 at risk
HEADACHE	Nervous system disorders	CTCAEv4	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0012 events1 affected11 at risk
HOT FLASHES	Vascular disorders	CTCAEv4	Non-systematic Assessment	EG0003 events2 affected5 at risk EG0018 events8 affected11 at risk
HYPERGLYCEMIA	Metabolism and nutrition disorders	CTCAEv4	Non-systematic Assessment	EG0001 events1 affected5 at risk EG00113 events4 affected11 at risk
HYPERHIDROSIS	Skin and subcutaneous tissue disorders	CTCAEv4	Non-systematic Assessment	EG0003 events1 affected5 at risk EG0010 events0 affected11 at risk
HYPERTENSION	Vascular disorders	CTCAEv4	Non-systematic Assessment	EG0004 events4 affected5 at risk EG00112 events7 affected11 at risk
INSOMNIA	Psychiatric disorders	CTCAEv4	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0011 events1 affected11 at risk
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDER - OTHER, SPECIFY	Musculoskeletal and connective tissue disorders	CTCAEv4	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected11 at risk
MYALGIA	Musculoskeletal and connective tissue disorders	CTCAEv4	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected11 at risk
NAUSEA	Gastrointestinal disorders	CTCAEv4	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0015 events4 affected11 at risk
NERVOUS SYSTEM DISORDERS - OTHER, SPECIFY	Nervous system disorders	CTCAEv4	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0011 events1 affected11 at risk
PAIN	General disorders	CTCAEv4	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0014 events3 affected11 at risk
SPASTICITY	Nervous system disorders	CTCAEv4	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected11 at risk
URINARY INCONTINENCE	Renal and urinary disorders	CTCAEv4	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected11 at risk
URINARY RETENTION	Renal and urinary disorders	CTCAEv4	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0011 events1 affected11 at risk
URINARY TRACT INFECTION	Infections and infestations	CTCAEv4	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected11 at risk
URINARY URGENCY	Renal and urinary disorders	CTCAEv4	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0011 events1 affected11 at risk
AGITATION	Psychiatric disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
ALANINE AMINOTRANSFERASE INCREASED	Investigations	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0015 events3 affected11 at risk
AMNESIA	Nervous system disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
ANOREXIA	Metabolism and nutrition disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
ANORGASMIA	Psychiatric disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
ANXIETY	Psychiatric disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
ARTHRITIS	Musculoskeletal and connective tissue disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
ASPARTATE AMINOTRANSFERASE INCREASED	Investigations	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0014 events3 affected11 at risk
BONE PAIN	Musculoskeletal and connective tissue disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0014 events3 affected11 at risk
CHOLESTEROL HIGH	Investigations	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
DIARRHEA	Gastrointestinal disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0018 events4 affected11 at risk
DIZZINESS	Nervous system disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0014 events3 affected11 at risk
EDEMA LIMBS	General disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0013 events2 affected11 at risk
EYE DISORDERS - OTHER, SPECIFY	Eye disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0014 events4 affected11 at risk
FLANK PAIN	Musculoskeletal and connective tissue disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
FLUSHING	Vascular disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
GYNECOMASTIA	Reproductive system and breast disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
HEARING IMPAIRED	Ear and labyrinth disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0012 events2 affected11 at risk
HEMATURIA	Renal and urinary disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
HYPOTHYROIDISM	Endocrine disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
INFECTIONS AND INFESTATIONS - OTHER, SPECIFY	Infections and infestations	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
INJURY, POISONING AND PROCEDURAL COMPLICATIONS - OTHER, SPECIFY	Injury, poisoning and procedural complications	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
INVESTIGATIONS - OTHER, SPECIFY	Investigations	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
LIBIDO DECREASED	Psychiatric disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
LYMPHOCYTE COUNT DECREASED	Investigations	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0012 events2 affected11 at risk
METABOLISM AND NUTRITION DISORDERS - OTHER, SPECIFY	Metabolism and nutrition disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
PAIN IN EXTREMITY	Musculoskeletal and connective tissue disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0015 events2 affected11 at risk
PARESTHESIA	Nervous system disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
PELVIC PAIN	Reproductive system and breast disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
PLATELET COUNT DECREASED	Investigations	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0015 events2 affected11 at risk
PRODUCTIVE COUGH	Respiratory, thoracic and mediastinal disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
PSYCHIATRIC DISORDERS - OTHER, SPECIFY	Psychiatric disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
RENAL AND URINARY DISORDERS - OTHER, SPECIFY	Renal and urinary disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0014 events4 affected11 at risk
RENAL CALCULI	Renal and urinary disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
REPRODUCTIVE SYSTEM AND BREAST DISORDERS - OTHER, SPECIFY	Reproductive system and breast disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - OTHER, SPECIFY	Respiratory, thoracic and mediastinal disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
SINUS BRADYCARDIA	Cardiac disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
SKIN AND SUBCUTANEOUS TISSUE DISORDERS - OTHER, SPECIFY	Skin and subcutaneous tissue disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0014 events2 affected11 at risk
SLEEP APNEA	Respiratory, thoracic and mediastinal disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0012 events2 affected11 at risk
TOOTH INFECTION	Infections and infestations	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
URINARY FREQUENCY	Renal and urinary disorders	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0015 events5 affected11 at risk
WEIGHT GAIN	Investigations	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk
WHITE BLOOD CELL DECREASED	Investigations	CTCAEv4	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected11 at risk

ID	Term
D005834	Genital Neoplasms, Male
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D005832	Genital Diseases, Male
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D011469	Prostatic Diseases
D052801	Male Urogenital Diseases

ID	Term
D007987	Gonadotropin-Releasing Hormone
C053541	bicalutamide
C581106	radium Ra 223 dichloride

ID	Term
D010906	Pituitary Hormone-Releasing Hormones
D007028	Hypothalamic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D009479	Neuropeptides
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D009842	Oligopeptides
D009419	Nerve Tissue Proteins
D011506	Proteins

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Control Arm A	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle.	0	5	0	5	4	5
EG001	Experimental Arm B	All subjects will receive LHRH agonist/antagonist per dosage and route of administration specified by the treating physician. Bicalutamide, 50mg, PO will be administered daily. Cycles will be 28 days. Radium-223 dichloride, 50 kBq/kg body weight, will be administered as a bolus intravenous (IV) injection at intervals of every 28 days for up to 6 cycles. LHRH agonist/antagonist: Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle. Bicalutamide: Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle. Radium-223 dichloride: Radium-223 dichloride, 50 kBq (1.35 microcurie) per kg body weight intravenous (IV bolus) every 28 days for 6 injections	0	11	0	11	11	11