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

NCT02582749 | Terminated Phase 2 Results DMC

• 1 other identifier: HCRN GU13-170
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 12

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.

Conditions

Prostate Cancer; Bone Metastases; Prostate Neoplasms

Keywords

Androgen Deprivation Therapy; Androgen Receptor Antagonist; Radium-223 Dichloride; Placebo

Outcome Measures

Primary Outcomes (1)

• 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.

Secondary Outcomes (12)

• 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

• 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

• Secondary Neoplasms

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

• PSA Complete Response Rates

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

• PSA Partial Response Rates

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

Study Arms (2)

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

Interventions

LHRH agonist/antagonist DRUG

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

Also known as: Per treating physician

Control Arm A; Experimental Arm B

Bicalutamide DRUG

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

Also known as: Casodex

Control Arm A; Experimental Arm B

Radium-223 dichloride RADIATION

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

Experimental Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (12)

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

Phoenix, Arizona, 85004, United States

Location

Illinois CancerCare, P. C.

Peoria, Illinois, 61615, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

IU Health Central Indiana Cancer Centers

Indianapolis, Indiana, 46219, United States

Location

University of Iowa Hopital and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Metro Health Cancer Center

Wyoming, Michigan, 49519, United States

Location

GU Research Network, LLC

Omaha, Nebraska, 68130, United States

Location

Integrated Medical Professionals, PLLC

Lake Success, New York, 11042, United States

Location

University of Texas Medical Branch at Galveston

Galveston, Texas, 77555, United States

Location

Clement J. Zablocki VA Medical Center

Milwaukee, Wisconsin, 53295, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Gonadotropin-Releasing Hormone; bicalutamide; radium Ra 223 dichloride

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Limitations and Caveats

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

Results Point of Contact

• Title: Clinicaltrials.gov Results Coordinator
• Organization: Hoosier Cancer Research Network

jsmith@hoosiercancer.org

317.921.2050

Study Officials

• Ajjai Alva, M.D.

  Hoosier Cancer Research Network

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: October 16, 2015
• First Posted: October 21, 2015
• Study Start: April 1, 2016
• Primary Completion: September 14, 2017
• Study Completion: September 14, 2017
• Last Updated: July 11, 2022
• Results First Posted: July 9, 2019

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)