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Pharmacodynamic Study of Radium-223 in Men With Bone Metastatic Castration-Resistant Prostate Cancer

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ClinicalTrials.gov Identifier: NCT02204943
Recruitment Status : Completed
First Posted : July 31, 2014
Last Update Posted : June 8, 2018
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Duke University

Brief Summary:

This study will examine biomarkers involved in osteomimicry in bone metastases and circulating tumor cells (CTCs) of men with mCRPC before and during therapy with the bone-targeting radiopharmaceutical radium-223. This study will also examine the bio-distribution of radium-223 in bone and bone metastases of men with mCRPC.

The investigators hypothesize that bone metastases and CTCs in men with mCRPC will commonly express markers of EMT/plasticity and osteomimicry, not just in the normal surrounding osteoblastic stroma but in the epithelial tumor cells themselves and that radium-223 will target both of these compartments including the more mesenchymal/osteoblastic tumor cells and the surrounding osteoblasts in the active bone microenvironment, with a relative sparing of normal bone and bone marrow.


Condition or disease Intervention/treatment Phase
Bone Metastatic Castration-Resistant Prostate Cancer Device: Biomarker analysis Drug: Administration of radium-223 Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Pharmacodynamic Study of Radium-223 in Men With Bone Metastatic Castration-Resistant Prostate Cancer
Actual Study Start Date : May 6, 2015
Actual Primary Completion Date : July 31, 2017
Actual Study Completion Date : July 31, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Bone Biopsy and Circulating Tumor Cell Samples Device: Biomarker analysis
Pharmacodynamic study of Radium-223 in bone biopsy and circulating tumor cell samples

Drug: Administration of radium-223
Subjects will receive radium-223 treatment for their disease as standard of care in this protocol. They will be receiving this treatment regardless of their participation in this protocol.




Primary Outcome Measures :
  1. Proportion of patients who overexpress alkaline phosphatase (ALP) in Circulating Tumor Cells (CTCs) at each time point [ Time Frame: Cycle 1 Day 1, Cycle 3 Day 1 and Cycle 6 Day 1 or disease progression ]
    The proportion of patients who over-express ALP in the CTCs, defined as any over-expression, will be estimated using descriptive statistics at each time point. ALP expression will be concurrently examined in the bone metastatic biopsies of men as well, if evaluable tissue is available.


Secondary Outcome Measures :
  1. Change in biomarkers of epithelial plasticity and osteomimicry expressed in the bone metastases of men with bone metastatic CRPC [ Time Frame: At time of optional biopsy, pre- and post-treatment with Radium-223. Post-treatment biopsies will be approximately 10 and 22 weeks after first treatment. ]
    Summary statistics of other biomarkers involved in epithelial plasticity and osteomimicry in the tumor tissue of men with bone metastatic CRPC including expression of ALP, PSA, CK, O-cadherin, N-cadherin, vimentin, TWIST, SNAIL, beta-catenin, ZEB1, androgen receptor (AR), AR variants (ARv) and γ-H2AX will be completed.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years.
  2. Life expectancy of at least 12 weeks (3 months).
  3. Subjects must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.
  4. Histologically confirmed diagnosis of adenocarcinoma of the prostate. Histologic variants of prostate cancer, including neuroendocrine features are permitted; however, pure small cell carcinoma of the prostate is excluded.
  5. Presence of >2 sites of metastatic disease in bone as determined by bone scan or CT, and for men who opt-in for bone biopsy, they must have at least one site amenable to radiographically-guided metastatic biopsy as determined by the study radiologist.
  6. Symptomatic castration-resistant bone metastatic disease as determined by the provider.
  7. Prior or concurrent therapy with either abiraterone acetate or enzalutamide.
  8. Ongoing ADT using an LHRH agonist (e.g. leuprolide, goserelin) or antagonist (e.g. degarelix) must continue on therapy unless prior bilateral orchiectomy has been performed.
  9. Current evidence of disease progression as evidenced by one of the following:

    1. 2 consecutive rising PSA levels separated at least 1 week apart above nadir PSA on last systemic therapy. If no nadir, then 2 rising PSA values greater than baseline pretreatment value is required from the most immediate prior therapy, OR
    2. CT or bone scan based evidence of disease progression with bone metastasis (new lesions or growth of existing lesions), OR
    3. Evidence of symptomatic progression (increased pain in an area with known lesions confirmed on imaging).
  10. All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v4.0 Grade 2 or less.
  11. Men of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF until at least 30 days after the last dose of study drug. The definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate.
  12. Acceptable hematology and serum biochemistry screening values:

    • White Blood Cell Count (WBC) ≥ 3,000/mm3
    • Absolute Neutrophil Count (ANC) ≥ 1,500/mm3
    • Platelet (PLT) count ≥ 100,000/mm3
    • Hemoglobin (HGB) ≥ 9.0 g/dl
    • Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN)
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
    • Creatinine ≤ 1.5 x ULN
    • Albumin > 2.5 g/dL
  13. Willing and able to comply with the protocol, including follow-up visits and examinations

Exclusion Criteria:

  1. Treatment with cytotoxic chemotherapy within previous 4 weeks, or failure to recover from AEs down to grade 2 or less due to cytotoxic chemotherapy administered more than 4 weeks previous (however, ongoing neuropathy is permitted)
  2. Receiving concurrent systemic therapy with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188) for the treatment of bony metastases. Prior therapy with radium-223 is not permitted.
  3. Other malignancy treated within the last 3 years (except non melanoma skin cancer or low-grade superficial bladder cancer)
  4. Visceral (i.e. liver, lung, etc) metastases (pulmonary nodules ≤1cm are permitted) as assessed by chest, abdominal or pelvic computed tomography (CT) (or other imaging modality)
  5. Presence of active untreated CNS parenchymal or epidural spinal metastases
  6. Lymphadenopathy exceeding 3 cm in short-axis diameter
  7. Imminent spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI). Treatment should be completed for spinal cord compression.
  8. Any other serious illness or medical condition, such as but not limited to:

    • Any infection ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 Grade 2
    • Cardiac failure New York Heart Association (NYHA) III or IV
    • Crohn's disease or ulcerative colitis
    • Bone marrow dysplasia
    • Fecal incontinence
  9. Inability to comply with the protocol and/or not willing or not available for follow-up assessments.
  10. Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.
  11. Concurrent cytotoxic chemotherapy or anticancer therapies other than abiraterone, prednisone or other glucocorticoids, enzalutamide, androgen deprivation therapy, bisphosphonates, and denosumab.
  12. Concurrent use of another investigational drug or device therapy (i.e., outside of study treatment) during, or within 2 weeks of treatment initiation.
  13. Major surgery within 30 days prior to start of study drug.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02204943


Locations
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United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Bayer
Investigators
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Principal Investigator: Andrew Armstrong, MD Duke University
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT02204943    
Other Study ID Numbers: Pro00053925
First Posted: July 31, 2014    Key Record Dates
Last Update Posted: June 8, 2018
Last Verified: June 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases