We updated the design of this site on September 25th. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Biomarker Study of Standard-of-care Radium-223 Chloride for Metastatic Castration-resistant Prostate Cancer

This study is currently recruiting participants.
Verified August 2017 by Philip J. Saylor, MD, Massachusetts General Hospital
Sponsor:
ClinicalTrials.gov Identifier:
NCT02346526
First Posted: January 27, 2015
Last Update Posted: August 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Bayer
Information provided by (Responsible Party):
Philip J. Saylor, MD, Massachusetts General Hospital
  Purpose
The purpose of this study is to look for markers of how Ra-223 improves the lives of men with prostate cancer. This study makes use of Ra-223 in the standard FDA-approved way, but adds non-standard testing in an attempt to gain insight about how the drug works and how best to track patients who are receiving the drug.

Condition Intervention Phase
Prostate Cancer Castration-resistant Prostate Cancer Castration-resistant Prostate Cancer Metastatic to Bone Procedure: Blood Tests Procedure: CT scan and bone scan Procedure: FACBC PET/MRI in a subset of participants Drug: Radium-223 dichloride Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single-arm Open Label Biomarker Study of Standard-of-care Radium-223 Chloride for Metastatic Castration-resistant Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Philip J. Saylor, MD, Massachusetts General Hospital:

Primary Outcome Measures:
  • Change from baseline in bone scan index at 2 months [ Time Frame: Baseline to 2 Months ]
    Bone scan index (BSI) will be used to quantitatively assess effect of therapy


Secondary Outcome Measures:
  • Mean percent change in bone scan lesion area by 18 month survival status [ Time Frame: 2 months (change in bone scan lesion area), 18 Months (survival status) ]
    Mean change in bone scan index (BSI) at 2 months (i.e. approximately week 9) as assessed by BSI will be described by 18 month survival status. In other words, decline in BSI at 2 months on therapy will be evaluated as a predictive biomarker of survival at 18 months.

  • Changes in circulating tumor cell (CTC) number [ Time Frame: Day 1, day 4, weeks 5, 9, 13, 17, 21, 25, 37, 93 ]
    CTCs will be assessed by FDA-approved assay (Veridex CellSearch)

  • Circulating biomarkers of the tumor microenvironment [ Time Frame: Day 1, day 4, weeks 5, 9, 13, 17, 21, 25, 37, 93 ]
    Bone turnover markers and plasma biomarkers of inflammation and angiogenesis will be assessed serially

  • Changes in circulating tumor cell (CTC) number and translational biomarkers [ Time Frame: Day 1, day 4, weeks 5, 9, 13, 17, 21, 25, 37, 93 ]
    CTCs will be assessed by an experimental microfluidic platform


Estimated Enrollment: 22
Actual Study Start Date: April 2015
Estimated Study Completion Date: July 2021
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Radium-223 dichloride

After the screening procedures confirm that a patient is eligible to participate in the research study.

Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments. These treatments are designed to be entirely standard. Extra testing during and after that six month period will be added to standard testing and monitoring.

  • Blood Tests
  • CT scan and bone scan
  • FACBC PET/MRI in a subset of participants
Procedure: Blood Tests
Blood will be drawn for standard and nonstandard testing on day one, day 4, and weeks 5, 9, 13, 17, 21, 25, 37, and 93.
Procedure: CT scan and bone scan
Standard CT and bone scans will be carried out prior to treatment, week 9, and week 25.
Procedure: FACBC PET/MRI in a subset of participants
Approximately half of the study patients (n=10) will undergo experimental FACBC PET/MRI testing at 2 time points each: (1) prior to therapy, and (2) week 9.
Drug: Radium-223 dichloride
Ra-223- Each treatment cycle lasts 4 weeks during which the patient receives Ra-223 at a dose of 50 kBq/kg body weight by intravenous infusion on day 1 only. Treatments are given every 4 weeks for a total of 6 treatments.
Other Name: Xofigo

Detailed Description:

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

This research study is designed to examine a treatment strategy that is standard but still relatively new. Ra-223 consists of a series of six infusions given once every 4 weeks. It was FDA approved in 2013 for the treatment of prostate cancer that has spread to bone and has grown despite ADT ("hormonal therapy").

Ra-223 was approved because it was shown to improve the length of the lives of the men with prostate cancer who received it. Despite that important benefit, it is not known to improve other standard markers of prostate cancer such as PSA blood tests (a blood marker that is used to track cancer activity in men who have prostate cancer) and standard imaging scans such as bone scans and computed tomography (CT) scans. If participants and their doctors do not have good markers of whether or not the cancer is responding to therapy, it is harder to make decisions about whether to continue that therapy. This is a current problem.

This study makes use of Ra-223 in the standard FDA-approved way, but adds non-standard testing in an attempt to gain insight about how the drug works and how best to track patients who are receiving the drug.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Male age ≥ 18 years.
  • Histologically or cytologically confirmed adenocarcinoma of the prostate. Life expectancy of at least 6 months.
  • ECOG performance status of zero, one, or two.
  • Bone-predominant metastatic CRPC: at least two skeletal metastases on bone scan with no lung, liver, and/or brain metastasis (lymph node metastasis is allowed).
  • Symptomatic as defined by either of the following:

    • (a) Regular use of analgesic medication for cancer-related bone pain (≥ level 1; WHO ladder for cancer pain), or
    • (b) Treatment with EBRT for bone pain (though EBRT must be completed ≥12 weeks prior to enrollment in this trial).
  • Judged by investigator to have progressive disease sufficient to clinically justify standard-of-care radium-223 treatment.
  • Subjects must be able to understand and be willing to sign the written informed consent form.
  • All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v4.0 Grade 1 or less at the time of signing the Informed Consent Form (ICF).
  • No intention to use cytotoxic chemotherapy within the next 6 months. Subjects must agree to use adequate contraception beginning at the signing of the ICF until at least 6 months after the last dose of study drug. The definition of adequate contraception will be based on the judgment of the principal investigator.
  • 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) ≥10 g/dl (Please note: it is acceptable from the standpoint of study eligibility to undergo transfusion in order to achieve hemoglobin ≥ 10 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 > 25 g/L
  • Willing and able to comply with the protocol, including follow-up visits and examinations.

Exclusion Criteria:

  • Treatment with cytotoxic chemotherapy within previous 28 days, or failure to recover from AEs due to cytotoxic chemotherapy administered more than 28 days previous (however, ongoing neuropathy is permitted).
  • Received any investigational compound within 28 days prior to the first dose of study drug or planned during the treatment period or follow-up.
  • Received systemic therapy with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188, or Radium Ra 223 dichloride) for the treatment of bony metastases.
  • Received previous radiotherapy to approximately >25% of bone marrow.
  • Other malignancy treated within the last 3 years (except non melanoma skin cancer or low-grade superficial bladder cancer).
  • Visceral metastases as assessed by abdominal or pelvic computed tomography (CT) or other imaging modality.
  • Presence of brain metastases.
  • Lymphadenopathy exceeding 6 cm in short-axis diameter.
  • Any size pelvic lymphadenopathy if it is thought to be a contributor to concurrent hydronephrosis.
  • Imminent spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI). Treatment should be completed for spinal cord compression.
  • 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 4.03 Grade 2
    • Cardiac failure New York Heart Association (NYHA) III or IV
    • Crohn's disease or ulcerative colitis
    • Known bone marrow dysplasia
  • Fecal incontinence.
  • Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.
  Contacts and Locations
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): NCT02346526


Contacts
Contact: Philip J Saylor, MD 617-724-4000 psaylor@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Philip J Saylor, MD    617-724-4000    psaylor@partners.org   
Principal Investigator: Philip J Saylor, MD         
Sponsors and Collaborators
Massachusetts General Hospital
Bayer
Investigators
Principal Investigator: Philip J Saylor, MD Massachusetts General Hospital
  More Information

Responsible Party: Philip J. Saylor, MD, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02346526     History of Changes
Other Study ID Numbers: 14-375
ONC-2013-119 ( Other Identifier: Bayer )
First Submitted: January 13, 2015
First Posted: January 27, 2015
Last Update Posted: August 7, 2017
Last Verified: August 2017

Keywords provided by Philip J. Saylor, MD, Massachusetts General Hospital:
Prostate Cancer
Castration-resistant prostate cancer
Castration-resistant prostate cancer metastatic to bone

Additional relevant MeSH terms:
Prostatic Neoplasms
Bone Neoplasms
Bone Marrow Diseases
Neoplasm Metastasis
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Bone Diseases
Musculoskeletal Diseases
Hematologic Diseases
Neoplastic Processes
Pathologic Processes
Radium Ra 223 dichloride
Antineoplastic Agents