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

NCT ID: NCT02582749

Last Updated: 2022-07-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-30
• Study Completion Date: 2017-09-14

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.

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

Conditions

Prostate Cancer; Bone Metastases; Prostate Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

LHRH agonist/antagonist

Intervention Type: DRUG

Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle.

Bicalutamide

Intervention Type: DRUG

Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle.

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.

Group Type: EXPERIMENTAL

LHRH agonist/antagonist

Intervention Type: DRUG

Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle.

Bicalutamide

Intervention Type: DRUG

Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle.

Radium-223 dichloride

Intervention Type: RADIATION

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

Interventions

LHRH agonist/antagonist

Treating physician will determine LHRH agonist/antagonist, dosage and route of administration, per package insert, during each 28-day cycle.

Intervention Type: DRUG

Bicalutamide

Bicalutamide, 50 mg Oral (PO) will be administered daily in each 28-day cycle.

Intervention Type: DRUG

Radium-223 dichloride

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

Intervention Type: RADIATION

Other Intervention Names

Per treating physician; Casodex

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Hoosier Cancer Research Network

OTHER

Sponsor Role: collaborator

Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma

INDUSTRY

Sponsor Role: collaborator

Ajjai Alva, MD

OTHER

Sponsor Role: lead

Responsible Party

Ajjai Alva, MD

Sponsor-Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ajjai Alva, M.D.

Role: STUDY_CHAIR

Hoosier Cancer Research Network

Locations

University of Arizona Cancer Center at Dignity Health St. Joseph's

Phoenix, Arizona, United States

Illinois CancerCare, P. C.

Peoria, Illinois, United States

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

IU Health Central Indiana Cancer Centers

Indianapolis, Indiana, United States

University of Iowa Hopital and Clinics

Iowa City, Iowa, United States

University of Michigan Health System

Ann Arbor, Michigan, United States

Henry Ford Hospital

Detroit, Michigan, United States

Metro Health Cancer Center

Wyoming, Michigan, United States

GU Research Network, LLC

Omaha, Nebraska, United States

Integrated Medical Professionals, PLLC

Lake Success, New York, United States

University of Texas Medical Branch at Galveston

Galveston, Texas, United States

Clement J. Zablocki VA Medical Center

Milwaukee, Wisconsin, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

HCRN GU13-170

Identifier Type: -

Identifier Source: org_study_id