<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03304418</url>
  </required_header>
  <id_info>
    <org_study_id>HCI102312</org_study_id>
    <nct_id>NCT03304418</nct_id>
  </id_info>
  <brief_title>Radium-223 and Radiotherapy in Hormone-Naïve Men With Oligometastatic Prostate Cancer to Bone</brief_title>
  <acronym>RROPE</acronym>
  <official_title>A Phase 2 Study of Radium-223 and Radiotherapy in Hormone-Naïve Men With Oligometastatic Prostate Cancer to Bone</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Utah</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bayer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Utah</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase IIa, open label, single arm, and prospective study of hormone therapy-naïve&#xD;
      men with oligometastatic prostate cancer to the bone. The study will test if treating the&#xD;
      primary tumor sites and 5 or fewer sites of bone-only metastasis with external beam radiation&#xD;
      with concomitant systemic Radium-223 will reduce the utilization of androgen deprivation&#xD;
      therapy, improve QOL and improve OS over a the comparator cohort of SWOG intermittent ADT&#xD;
      historic cohort.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 27, 2018</start_date>
  <completion_date type="Anticipated">August 2024</completion_date>
  <primary_completion_date type="Anticipated">November 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>This is a phase IIa, open label, single arm, prospective study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to Androgen Deprivation Therapy (ADT) Use</measure>
    <time_frame>15 months</time_frame>
    <description>Determine if 20% of ADT naïve men treated with concurrent EBRT and Radium-223 will not require ADT for progression by 15 months.&#xD;
Endpoint: Determine the time from start of study therapy to start of ADT.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time from start of study therapy to start of ADT.</measure>
    <time_frame>2 years</time_frame>
    <description>Determine the hormone-therapy free survival time for men treated with concurrent EBRT and Radium-223 and determine if it is a 30% risk reduction over the SWOG intermittent ADT historic cohort</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate health related quality of life (QOL)</measure>
    <time_frame>This questionnaire will be given every 3 months for 2 years</time_frame>
    <description>Evaluate health related quality of life (QOL) as scored by the 50 item Expanded Prostate Inventory Composite (EPIC) EPIC urinary, bowel, sexual and hormonal domains.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate changes in general function and well being</measure>
    <time_frame>This questionnaire will be given every 3 months for 2 years</time_frame>
    <description>Evaluate health related quality of life (QOL)- the PROMIS 29 will be used to assess general function and well-being</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate time to first skeletal related event (SRE)</measure>
    <time_frame>2 years</time_frame>
    <description>Documentation of complications associated with bone metastases and may include (but not limited to) fractures, spinal cord compression, bone pain, and hypercalcemia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the PSA doubling time</measure>
    <time_frame>2 years, assessed at every visit in that time period</time_frame>
    <description>Time elapsed from baseline PSA to double in value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate Overall Surival</measure>
    <time_frame>2 years</time_frame>
    <description>Evaluate overall survival at 2 years relative to the SWOG intermittent ADT historic cohort.&#xD;
Endpoint: Patients will be followed for survival for two years after study enrollment</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Prostate Cancer Metastatic to Bone</condition>
  <arm_group>
    <arm_group_label>Radium Ra 223 dichloride and radiation, all patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Radium Ra 223 Dichloride</intervention_name>
    <description>Radium Ra 223 dichloride will be delivered intravenously at 55 kBq/kg (1.49 mCi)/kg (+/- 10% total dose) for a total of six cycles. 1 cycle= 28 days. The first cycle will commence at study enrollment, then cycles 2-6 will commence after the completion of radiotherapies at 4 week intervals</description>
    <arm_group_label>Radium Ra 223 dichloride and radiation, all patients</arm_group_label>
    <other_name>Xofigo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiation</intervention_name>
    <description>All external beam radiations oligometastatic sites will commence after cycle 1 of Radium-223 but prior to cycle 2 of Radium-223. All subjects will receive Stereotactic body or hypofractionated radiation to sites of bone disease seen on imaging studies. Patients will have the primary tumor sites and 5 or fewer sites of bone-only metastasis treated with external beam radiation.&#xD;
Any of the following regimens are considered ablative, acceptable and are biologically equivalent to 60Gy EQD2:&#xD;
Single fraction: 16 Gy total at 16 Gy per fraction (SBRT)&#xD;
Three fractions: 24 Gy total at 8 Gy per fraction (SBRT)&#xD;
Five fractions: 30 Gy total at 6Gy per fraction (SBRT).When using five fractions, can reduce to 25 Gy total at 5 Gy per fraction (SBRT) or to a minimum of 20 Gy total at 4 Gy per fraction (SBRT), per treating investigator.&#xD;
Six fractions: 32.4 Gy total at 5.4Gy per fraction (Hypofractionated)</description>
    <arm_group_label>Radium Ra 223 dichloride and radiation, all patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Asymptomatic or symptomatic hormone naïve men with testosterone levels ≥100 ng/dL with&#xD;
             previously treated localized prostate cancer who now have rising PSA's and five or&#xD;
             fewer bone metastases.&#xD;
&#xD;
          -  Subjects who have been previously treated with definitive and/or adjuvant/salvage&#xD;
             radiotherapy to the primary site and/or regional lymph nodes with concurrent ADT are&#xD;
             allowed if the last hormone therapy delivered &gt; 6 months prior. Subjects who have had&#xD;
             more than 30 days and fewer than 45 days of bicalutamide monotherapy for any reason&#xD;
             within the 6 months prior to enrollment are eligible for the study, providing they&#xD;
             have been off of the drug for at least 30 days prior to enrollment. Subjects who have&#xD;
             had fewer than 30 days of bicalutamide are eligible for the study, as long as they&#xD;
             discontinue the drug at least 5 days prior to the first study treatment.&#xD;
&#xD;
          -  Histologic confirmation of Prostate Adenocarcinoma diagnosis.&#xD;
&#xD;
          -  Age ≥ 18 years.&#xD;
&#xD;
          -  Life expectancy of at least 2 years.&#xD;
&#xD;
          -  Acceptable hematology and serum biochemistry screening values:&#xD;
&#xD;
               -  White Blood Cell Count (WBC) ≥ 3,000/mm3&#xD;
&#xD;
               -  Absolute Neutrophil Count (ANC) ≥ 1,500/mm3&#xD;
&#xD;
               -  Platelet (PLT) count ≥ 100,000/mm3&#xD;
&#xD;
               -  Hemoglobin (HGB) ≥ 10 g/dl&#xD;
&#xD;
               -  Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN)&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN&#xD;
&#xD;
               -  Creatinine ≤ 1.5 x ULN&#xD;
&#xD;
               -  Albumin &gt; 2.5 mg/dL&#xD;
&#xD;
          -  Willing and able to comply with the protocol, including follow-up visits and&#xD;
             examinations.&#xD;
&#xD;
          -  Karnofsky Performance Score &gt;60 or ECOG equivalent.&#xD;
&#xD;
          -  Radiographic confirmation of oligometastatic diagnosis via Bone Scan validated by&#xD;
             either CT scan or MRI or PET/CT with Fluciclovine within the past 90 days.&#xD;
&#xD;
          -  Subjects who have not had surgical removal of their prostate and have a partner of&#xD;
             child bearing potential must agree to use condoms beginning at the signing of the ICF&#xD;
             until at least 6 months after the last dose of study drug. Because of the potential&#xD;
             side effect on spermatogenesis associated with radiation, female partners of&#xD;
             childbearing potential must agree to use a highly effective contraceptive method&#xD;
             during and for 6 months after completing treatment&#xD;
&#xD;
          -  Able to provide informed consent and willing to sign an approved consent form that&#xD;
             conforms to federal and institutional guidelines.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Men with known brain or visceral metastases (except regional lymph nodes as defined by&#xD;
             section 5.2.5) defined by CT or MRI Imaging of the abdomen or pelvis.&#xD;
&#xD;
          -  Men who have had LHRH agonist or antagonist hormone therapy in the prior six months.&#xD;
&#xD;
          -  Men with &gt;5 bony metastases.&#xD;
&#xD;
          -  Men with baseline serum Testosterone &lt;100 ng/dL.&#xD;
&#xD;
          -  Men with new or progressing lymphadenopathy clearly consistent with prostate&#xD;
             metastasis on imaging or proven by pathologic biopsy at any time three months or later&#xD;
             following their initial definitive therapy.&#xD;
&#xD;
          -  Prior or concurrent invasive malignancy (except non-melanomatous skin cancer) or&#xD;
             lymphomatous/hematogenous malignancy unless continually disease free for a minimum of&#xD;
             3 years. All patients with in situ carcinoma are eligible for this study (for example,&#xD;
             carcinoma in situ of the oral cavity is eligible) except patients with carcinoma of&#xD;
             the bladder (including in situ bladder cancer or superficial bladder cancer).&#xD;
&#xD;
          -  Use of finasteride within 30 days prior to therapy PSA should not be obtained prior to&#xD;
             30 days after stopping finasteride.&#xD;
&#xD;
          -  Use of dutasteride within 90 days prior to therapy. PSA should not be obtained prior&#xD;
             to 90 days after stopping dutasteride.&#xD;
&#xD;
          -  Previous or concurrent cytotoxic chemotherapy for prostate cancer.&#xD;
&#xD;
          -  Received systemic therapy with radionuclides (e.g., strontium-89, samarium-153,&#xD;
             rhenium-186, or rhenium-188, or Radium Ra 223 dichloride) for the treatment of bony&#xD;
             metastases.&#xD;
&#xD;
          -  Men who will receive radical prostatectomy to the primary site.&#xD;
&#xD;
          -  Imminent spinal cord compression based on clinical findings and/or magnetic resonance&#xD;
             imaging (MRI). Spinal Cord compression will be defined as 360 degree circumferential&#xD;
             obliteration of T2 cerebrospinal fluid signal around the spinal cord. Treatment should&#xD;
             be completed for spinal cord compression.&#xD;
&#xD;
          -  Severe, active co-morbidity, defined as follows:&#xD;
&#xD;
               -  Unstable angina and/or congestive heart failure requiring hospitalization within&#xD;
                  the last 6 months&#xD;
&#xD;
               -  Transmural myocardial infarction within the last 6 months&#xD;
&#xD;
               -  Acute bacterial or fungal infection requiring intravenous antibiotics at the time&#xD;
                  of registration&#xD;
&#xD;
               -  Chronic obstructive pulmonary disease exacerbation or other respiratory illness&#xD;
                  requiring hospitalization or precluding study therapy at the time of registration&#xD;
&#xD;
               -  Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;&#xD;
                  note, however, that laboratory tests for liver function and coagulation&#xD;
                  parameters are not required for entry into this protocol. (Patients on Coumadin&#xD;
                  or other blood thinning agents are eligible for this study.)&#xD;
&#xD;
               -  Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition;&#xD;
                  note, however, that HIV testing is not required for entry into this protocol. The&#xD;
                  need to exclude patients with AIDS from this protocol is necessary because the&#xD;
                  treatments involved in this protocol may be significantly immunosuppressive.&#xD;
&#xD;
          -  Cardiac failure New York Heart Association (NYHA) III or IV Crohn's disease or&#xD;
             ulcerative colitis.&#xD;
&#xD;
          -  Bone marrow dysplasia.&#xD;
&#xD;
          -  Fecal incontinence.&#xD;
&#xD;
          -  Any condition which, in the investigator's opinion, makes the subject unsuitable for&#xD;
             trial participation.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Huntsman Cancer Institute</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>September 27, 2017</study_first_submitted>
  <study_first_submitted_qc>October 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 9, 2017</study_first_posted>
  <last_update_submitted>August 2, 2023</last_update_submitted>
  <last_update_submitted_qc>August 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Radium Ra 223 dichloride</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03304418
org study id: HCI102312
nct id: NCT03304418
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is a phase IIa, open label, single arm, and prospective study of hormone therapy-naïve
      men with oligometastatic prostate cancer to the bone. The study will test if treating the
      primary tumor sites and 5 or fewer sites of bone-only metastasis with external beam radiation
      with concomitant systemic Radium-223 will reduce the utilization of androgen deprivation
      therapy, improve QOL and improve OS over a the comparator cohort of SWOG intermittent ADT
      historic cohort.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This is a phase IIa, open label, single arm, prospective study
primary purpose: Treatment
masking: None (Open Label)
measure: Time to Androgen Deprivation Therapy (ADT) Use
time frame: 15 months
description: Determine if 20% of ADT naïve men treated with concurrent EBRT and Radium-223 will not require ADT for progression by 15 months.
Endpoint: Determine the time from start of study therapy to start of ADT.
measure: Time from start of study therapy to start of ADT.
time frame: 2 years
description: Determine the hormone-therapy free survival time for men treated with concurrent EBRT and Radium-223 and determine if it is a 30% risk reduction over the SWOG intermittent ADT historic cohort
measure: Evaluate health related quality of life (QOL)
time frame: This questionnaire will be given every 3 months for 2 years
description: Evaluate health related quality of life (QOL) as scored by the 50 item Expanded Prostate Inventory Composite (EPIC) EPIC urinary, bowel, sexual and hormonal domains.
measure: Evaluate changes in general function and well being
time frame: This questionnaire will be given every 3 months for 2 years
description: Evaluate health related quality of life (QOL)- the PROMIS 29 will be used to assess general function and well-being
measure: Evaluate time to first skeletal related event (SRE)
time frame: 2 years
description: Documentation of complications associated with bone metastases and may include (but not limited to) fractures, spinal cord compression, bone pain, and hypercalcemia.
measure: Evaluate the PSA doubling time
time frame: 2 years, assessed at every visit in that time period
description: Time elapsed from baseline PSA to double in value.
measure: Evaluate Overall Surival
time frame: 2 years
description: Evaluate overall survival at 2 years relative to the SWOG intermittent ADT historic cohort.
Endpoint: Patients will be followed for survival for two years after study enrollment
arm group label: Radium Ra 223 dichloride and radiation, all patients
arm group type: Experimental
intervention type: Drug
intervention name: Radium Ra 223 Dichloride
description: Radium Ra 223 dichloride will be delivered intravenously at 55 kBq/kg (1.49 mCi)/kg (+/- 10% total dose) for a total of six cycles. 1 cycle= 28 days. The first cycle will commence at study enrollment, then cycles 2-6 will commence after the completion of radiotherapies at 4 week intervals
arm group label: Radium Ra 223 dichloride and radiation, all patients
other name: Xofigo
intervention type: Radiation
intervention name: Radiation
description: All external beam radiations oligometastatic sites will commence after cycle 1 of Radium-223 but prior to cycle 2 of Radium-223. All subjects will receive Stereotactic body or hypofractionated radiation to sites of bone disease seen on imaging studies. Patients will have the primary tumor sites and 5 or fewer sites of bone-only metastasis treated with external beam radiation.
Any of the following regimens are considered ablative, acceptable and are biologically equivalent to 60Gy EQD2:
Single fraction: 16 Gy total at 16 Gy per fraction (SBRT)
Three fractions: 24 Gy total at 8 Gy per fraction (SBRT)
Five fractions: 30 Gy total at 6Gy per fraction (SBRT).When using five fractions, can reduce to 25 Gy total at 5 Gy per fraction (SBRT) or to a minimum of 20 Gy total at 4 Gy per fraction (SBRT), per treating investigator.
Six fractions: 32.4 Gy total at 5.4Gy per fraction (Hypofractionated)
arm group label: Radium Ra 223 dichloride and radiation, all patients
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Radium Ra 223 dichloride
sharing ipd: No