Androgen Deprivation Therapy +/- Radium-223 Dichloride in Metastatic Prostate Cancer With Bone Metastases

• Sponsor: Ajjai Alva, MD (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02582749
• Collaborator: Hoosier Cancer Research Network (Other), Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma (Industry)
• Enrollment: 16
• Locations: 12
• Arms: 2
• Actual Duration (Months): 17.4
• Patients Per Site: 1.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer; Bone Metastases; Prostate Neoplasms	Drug: LHRH agonist/antagonist; Drug: Bicalutamide; Radiation: Radium-223 dichloride	Phase 2

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 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

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Androgen Deprivation Therapy With or Without Radium-223 Dichloride in Patients With Newly Diagnosed Metastatic Prostate Cancer With Bone Metastases: Hoosier Cancer Research Network GU13-170
• Actual Study Start Date: Apr 1, 2016
• Actual Primary Completion Date: Sep 14, 2017
• Actual Study Completion Date: Sep 14, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Drug: LHRH agonist/antagonist; Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle.; Other Names: Per treating physician ; Drug: Bicalutamide; Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle.; Other Names: Casodex
Experimental: 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.	Drug: LHRH agonist/antagonist; Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle.; Other Names: Per treating physician ; Drug: Bicalutamide; Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle.; Other Names: Casodex ; Radiation: Radium-223 dichloride; Radium-223 dichloride, 50 kBq (1.35 microcurie) per kg body weight intravenous (IV bolus) every 28 days for 6 injections

Outcome Measures

Primary Outcome Measures

1. Radiological Progression-Free Survival (rPFS) [From date of randomization to disease progression or death from any cause, up to a maximum of 24 months.]

   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

Secondary Outcome Measures

1. 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) [From date of first dose until 30 days after the last treatment, assessed for a maximum of 24 months]

   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)

2. Time to First Skeletal-Related Event (SRE) [From date of first dose until 30 days after the last treatment, assessed for a maximum of 24 months]

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

3. Secondary Neoplasms [From date of first dose until 30 days after the last treatment, assessed for a maximum of 24 months]

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

4. PSA Complete Response Rates [From date of first dose of androgen deprivation therapy (ADT) until completion of 7 cycles (28 weeks)]

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

5. PSA Partial Response Rates [From date of first dose of ADT until completion of 7 cycles (28 weeks)]

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

6. Median Time to Castration Resistance [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]

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

7. 2-Year PSA Progression Free Survival (PFS) [From date of randomization to first occurrence of PSA progression, symptomatic deterioration, or death due to any cause, assessed up to 24 months]

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

8. 2-Year Overall Survival (OS) [From date of randomization to death from any cause, assessed up to 24 months]

   OS for subjects on both arms

9. 12-Week Alkaline Phosphatase (ALP) Normalization [From date of randomization until completion of 12 weeks of therapy]

   ALP normalization for subjects with abnormal ALP at randomization

10. Time to ALP Progression [From date of randomization until date of ALP progression, assessed up to 24 months]

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

11. Change in Pain Over Time [From baseline until 30 days after the last treatment, assessed for a maximum of 24 months]

    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.

12. Analgesic Use by WHO Ladder Score [From baseline until 30 days after the last treatment, assessed for a maximum of 24 months]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona Cancer Center at Dignity Health St. Joseph's	Phoenix	Arizona	United States	85004
2	Illinois CancerCare, P. C.	Peoria	Illinois	United States	61615
3	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
4	IU Health Central Indiana Cancer Centers	Indianapolis	Indiana	United States	46219
5	University of Iowa Hopital and Clinics	Iowa City	Iowa	United States	52242
6	University of Michigan Health System	Ann Arbor	Michigan	United States	48109
7	Henry Ford Hospital	Detroit	Michigan	United States	48202
8	Metro Health Cancer Center	Wyoming	Michigan	United States	49519
9	GU Research Network, LLC	Omaha	Nebraska	United States	68130
10	Integrated Medical Professionals, PLLC	Lake Success	New York	United States	11042
11	University of Texas Medical Branch at Galveston	Galveston	Texas	United States	77555
12	Clement J. Zablocki VA Medical Center	Milwaukee	Wisconsin	United States	53295

Sponsors and Collaborators

• Ajjai Alva, MD
• Hoosier Cancer Research Network
• Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma

Investigators

• Study Chair: Ajjai Alva, M.D., Hoosier Cancer Research Network

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 9, 2017

More Information

Publications

None provided.

• Responsible Party: Ajjai Alva, MD, Sponsor-Investigator, Hoosier Cancer Research Network
• ClinicalTrials.gov Identifier: NCT02582749
• Other Study ID Numbers: HCRN GU13-170
• First Posted: Oct 21, 2015
• Last Update Posted: Jul 11, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Ajjai Alva, MD, Sponsor-Investigator, Hoosier Cancer Research Network: Androgen Deprivation Therapy; Androgen Receptor Antagonist; Radium-223 Dichloride; Placebo
• Additional relevant MeSH terms: Prostatic Neoplasms; Neoplasm Metastasis; Bone Neoplasms; Bone Marrow Diseases; Bicalutamide; Radium Ra 223 dichloride

Study Results

Participant Flow

Arm/Group Title	Control Arm A	Experimental Arm B
Arm/Group Description	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.	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
Period Title: Overall Study
STARTED	5	11
COMPLETED	0	0
NOT COMPLETED	5	11

Baseline Characteristics

Arm/Group Title	Control Arm A	Experimental Arm B	Total
Arm/Group Description	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.	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	Total of all reporting groups
Overall Participants	5	11	16
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 60%	4 36.4%	7 43.8%
>=65 years	2 40%	7 63.6%	9 56.3%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	5 100%	11 100%	16 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	5 100%	11 100%	16 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	5 100%	11 100%	16 100%
Extent of Disease (Count of Participants)
<6 skel met, no visc met, total alk phos<=130 IU/L	2 40%	5 45.5%	7 43.8%
<6 skel met, no visc met, total alk phos >130IU/L	1 20%	1 9.1%	2 12.5%
>=6 skel met or visc met, total alk phos <=130IU/L	1 20%	4 36.4%	5 31.3%
>=6 skel met or visc met, total alk phos >130IU/L	1 20%	1 9.1%	2 12.5%

Outcome Measures

1. Primary Outcome

Title	Radiological Progression-Free Survival (rPFS)
Description	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
Time Frame	From date of randomization to disease progression or death from any cause, up to a maximum of 24 months.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Control Arm A	Experimental Arm B
Arm/Group Description	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.	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
Measure Participants	0	0

2. Secondary Outcome

Title	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)
Description	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)
Time Frame	From date of first dose until 30 days after the last treatment, assessed for a maximum of 24 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Control Arm A	Experimental Arm B
Arm/Group Description	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.	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
Measure Participants	0	0

3. Secondary Outcome

Title	Time to First Skeletal-Related Event (SRE)
Description	SRE of subjects on both arms assessed by bone scan or axial imaging
Time Frame	From date of first dose until 30 days after the last treatment, assessed for a maximum of 24 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Control Arm A	Experimental Arm B
Arm/Group Description	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.	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
Measure Participants	0	0

4. Secondary Outcome

Title	Secondary Neoplasms
Description	Secondary neoplasms of subjects on both arms assessed by bone scan or axial imaging
Time Frame	From date of first dose until 30 days after the last treatment, assessed for a maximum of 24 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Control Arm A	Experimental Arm B
Arm/Group Description	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.	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
Measure Participants	0	0

5. Secondary Outcome

Title	PSA Complete Response Rates
Description	Subjects on both arms with PSA ≤ 0.2 ng/mL after 7 months of androgen deprivation therapy
Time Frame	From date of first dose of androgen deprivation therapy (ADT) until completion of 7 cycles (28 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Control Arm A	Experimental Arm B
Arm/Group Description	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.	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
Measure Participants	0	0

6. Secondary Outcome

Title	PSA Partial Response Rates
Description	Subjects on both arms with PSA between 0.2 and ≤ 4 ng/mL after 7 months of androgen deprivation therapy.
Time Frame	From date of first dose of ADT until completion of 7 cycles (28 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Control Arm A	Experimental Arm B
Arm/Group Description	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.	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
Measure Participants	0	0

7. Secondary Outcome

Title	Median Time to Castration Resistance
Description	Castration resistance for subjects on both arms determined by first PSA level increase and/or radiographic progression by first imaging assessment showing progression
Time Frame	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Control Arm A	Experimental Arm B
Arm/Group Description	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.	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
Measure Participants	0	0

8. Secondary Outcome

Title	2-Year PSA Progression Free Survival (PFS)
Description	PSA PFS for subjects on both arms defined as first PSA level increase
Time Frame	From date of randomization to first occurrence of PSA progression, symptomatic deterioration, or death due to any cause, assessed up to 24 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Control Arm A	Experimental Arm B
Arm/Group Description	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.	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
Measure Participants	0	0

9. Secondary Outcome

Title	2-Year Overall Survival (OS)
Description	OS for subjects on both arms
Time Frame	From date of randomization to death from any cause, assessed up to 24 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Control Arm A	Experimental Arm B
Arm/Group Description	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.	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
Measure Participants	0	0

10. Secondary Outcome

Title	12-Week Alkaline Phosphatase (ALP) Normalization
Description	ALP normalization for subjects with abnormal ALP at randomization
Time Frame	From date of randomization until completion of 12 weeks of therapy

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Control Arm A	Experimental Arm B
Arm/Group Description	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.	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
Measure Participants	0	0

11. Secondary Outcome

Title	Time to ALP Progression
Description	ALP progression of 25% or greater from baseline/nadir for subjects on both arms
Time Frame	From date of randomization until date of ALP progression, assessed up to 24 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Control Arm A	Experimental Arm B
Arm/Group Description	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.	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
Measure Participants	0	0

12. Secondary Outcome

Title	Change in Pain Over Time
Description	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.
Time Frame	From baseline until 30 days after the last treatment, assessed for a maximum of 24 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Control Arm A	Experimental Arm B
Arm/Group Description	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.	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
Measure Participants	0	0

13. Secondary Outcome

Title	Analgesic Use by WHO Ladder Score
Description	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.
Time Frame	From baseline until 30 days after the last treatment, assessed for a maximum of 24 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Control Arm A	Experimental Arm B
Arm/Group Description	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.	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
Measure Participants	0	0

Adverse Events

Time Frame	Duration of participation in study, until study termination.
Arm/Group Title	Control Arm A		Experimental Arm B
Arm/Group Description	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.		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
All Cause Mortality
	Control Arm A		Experimental Arm B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/11 (0%)
Serious Adverse Events
	Control Arm A		Experimental Arm B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Control Arm A		Experimental Arm B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/5 (80%)		11/11 (100%)
Blood and lymphatic system disorders
ANEMIA	2/5 (40%)	2	5/11 (45.5%)	8
BLOOD AND LYMPHATIC SYSTEM DISORDERS - OTHER, SPECIFY	1/5 (20%)	1	1/11 (9.1%)	1
Cardiac disorders
SINUS BRADYCARDIA	0/5 (0%)	0	1/11 (9.1%)	1
Ear and labyrinth disorders
HEARING IMPAIRED	0/5 (0%)	0	2/11 (18.2%)	2
Endocrine disorders
HYPOTHYROIDISM	0/5 (0%)	0	1/11 (9.1%)	1
Eye disorders
EYE DISORDERS - OTHER, SPECIFY	0/5 (0%)	0	4/11 (36.4%)	4
Gastrointestinal disorders
ABDOMINAL PAIN	1/5 (20%)	2	2/11 (18.2%)	2
CONSTIPATION	3/5 (60%)	4	4/11 (36.4%)	4
GASTROESOPHAGEAL REFLUX DISEASE	1/5 (20%)	1	1/11 (9.1%)	1
NAUSEA	1/5 (20%)	1	4/11 (36.4%)	5
DIARRHEA	0/5 (0%)	0	4/11 (36.4%)	8
General disorders
FATIGUE	1/5 (20%)	1	7/11 (63.6%)	12
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - OTHER, SPECIFY	1/5 (20%)	1	0/11 (0%)	0
PAIN	1/5 (20%)	1	3/11 (27.3%)	4
EDEMA LIMBS	0/5 (0%)	0	2/11 (18.2%)	3
Infections and infestations
URINARY TRACT INFECTION	1/5 (20%)	1	0/11 (0%)	0
INFECTIONS AND INFESTATIONS - OTHER, SPECIFY	0/5 (0%)	0	1/11 (9.1%)	1
TOOTH INFECTION	0/5 (0%)	0	1/11 (9.1%)	1
Injury, poisoning and procedural complications
FALL	1/5 (20%)	1	0/11 (0%)	0
INJURY, POISONING AND PROCEDURAL COMPLICATIONS - OTHER, SPECIFY	0/5 (0%)	0	1/11 (9.1%)	1
Investigations
ALKALINE PHOSPHATASE INCREASED	1/5 (20%)	2	2/11 (18.2%)	2
ALANINE AMINOTRANSFERASE INCREASED	0/5 (0%)	0	3/11 (27.3%)	5
ASPARTATE AMINOTRANSFERASE INCREASED	0/5 (0%)	0	3/11 (27.3%)	4
CHOLESTEROL HIGH	0/5 (0%)	0	1/11 (9.1%)	1
INVESTIGATIONS - OTHER, SPECIFY	0/5 (0%)	0	1/11 (9.1%)	1
LYMPHOCYTE COUNT DECREASED	0/5 (0%)	0	2/11 (18.2%)	2
PLATELET COUNT DECREASED	0/5 (0%)	0	2/11 (18.2%)	5
WEIGHT GAIN	0/5 (0%)	0	1/11 (9.1%)	1
WHITE BLOOD CELL DECREASED	0/5 (0%)	0	1/11 (9.1%)	1
Metabolism and nutrition disorders
HYPERGLYCEMIA	1/5 (20%)	1	4/11 (36.4%)	13
ANOREXIA	0/5 (0%)	0	1/11 (9.1%)	1
METABOLISM AND NUTRITION DISORDERS - OTHER, SPECIFY	0/5 (0%)	0	1/11 (9.1%)	1
Musculoskeletal and connective tissue disorders
ARTHRALGIA	1/5 (20%)	1	0/11 (0%)	0
BACK PAIN	2/5 (40%)	2	3/11 (27.3%)	4
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDER - OTHER, SPECIFY	1/5 (20%)	1	0/11 (0%)	0
MYALGIA	1/5 (20%)	1	0/11 (0%)	0
ARTHRITIS	0/5 (0%)	0	1/11 (9.1%)	1
BONE PAIN	0/5 (0%)	0	3/11 (27.3%)	4
FLANK PAIN	0/5 (0%)	0	1/11 (9.1%)	1
PAIN IN EXTREMITY	0/5 (0%)	0	2/11 (18.2%)	5
Nervous system disorders
HEADACHE	1/5 (20%)	1	1/11 (9.1%)	2
NERVOUS SYSTEM DISORDERS - OTHER, SPECIFY	1/5 (20%)	1	1/11 (9.1%)	1
SPASTICITY	1/5 (20%)	1	0/11 (0%)	0
AMNESIA	0/5 (0%)	0	1/11 (9.1%)	1
DIZZINESS	0/5 (0%)	0	3/11 (27.3%)	4
PARESTHESIA	0/5 (0%)	0	1/11 (9.1%)	1
Psychiatric disorders
DEPRESSION	1/5 (20%)	1	1/11 (9.1%)	1
INSOMNIA	1/5 (20%)	1	1/11 (9.1%)	1
AGITATION	0/5 (0%)	0	1/11 (9.1%)	1
ANORGASMIA	0/5 (0%)	0	1/11 (9.1%)	1
ANXIETY	0/5 (0%)	0	1/11 (9.1%)	1
LIBIDO DECREASED	0/5 (0%)	0	1/11 (9.1%)	1
PSYCHIATRIC DISORDERS - OTHER, SPECIFY	0/5 (0%)	0	1/11 (9.1%)	1
Renal and urinary disorders
URINARY INCONTINENCE	1/5 (20%)	1	0/11 (0%)	0
URINARY RETENTION	1/5 (20%)	1	1/11 (9.1%)	1
URINARY URGENCY	1/5 (20%)	1	1/11 (9.1%)	1
HEMATURIA	0/5 (0%)	0	1/11 (9.1%)	1
RENAL AND URINARY DISORDERS - OTHER, SPECIFY	0/5 (0%)	0	4/11 (36.4%)	4
RENAL CALCULI	0/5 (0%)	0	1/11 (9.1%)	1
URINARY FREQUENCY	0/5 (0%)	0	5/11 (45.5%)	5
Reproductive system and breast disorders
ERECTILE DYSFUNCTION	1/5 (20%)	1	1/11 (9.1%)	1
GYNECOMASTIA	0/5 (0%)	0	1/11 (9.1%)	1
PELVIC PAIN	0/5 (0%)	0	1/11 (9.1%)	1
REPRODUCTIVE SYSTEM AND BREAST DISORDERS - OTHER, SPECIFY	0/5 (0%)	0	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders
DYSPNEA	1/5 (20%)	1	2/11 (18.2%)	2
PRODUCTIVE COUGH	0/5 (0%)	0	1/11 (9.1%)	1
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - OTHER, SPECIFY	0/5 (0%)	0	1/11 (9.1%)	1
SLEEP APNEA	0/5 (0%)	0	2/11 (18.2%)	2
Skin and subcutaneous tissue disorders
HYPERHIDROSIS	1/5 (20%)	3	0/11 (0%)	0
SKIN AND SUBCUTANEOUS TISSUE DISORDERS - OTHER, SPECIFY	0/5 (0%)	0	2/11 (18.2%)	4
Vascular disorders
HOT FLASHES	2/5 (40%)	3	8/11 (72.7%)	8
HYPERTENSION	4/5 (80%)	4	7/11 (63.6%)	12
FLUSHING	0/5 (0%)	0	1/11 (9.1%)	1

Limitations/Caveats

Study was terminated due to slow accrual. All subjects were removed from study before reaching any primary or secondary endpoints.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.