<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/NCT03230734</url>
  </required_header>
  <id_info>
    <org_study_id>IRST185.04</org_study_id>
    <secondary_id>2016-004452-29</secondary_id>
    <nct_id>NCT03230734</nct_id>
  </id_info>
  <brief_title>Sequencing of Radium-223 and Docetaxel in Symptomatic Bone-only Metastatic Castration-resistant Prostate Cancer</brief_title>
  <acronym>RAPSON</acronym>
  <official_title>Randomized, Multicentre Phase II Trial of the Sequencing of Radium-223 and Docetaxel Plus Prednisone in Symptomatic Bone-only Metastatic Castration-resistant Prostate Cancer (mCRPC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bayer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Randomized, multicentre phase II trial of the sequencing of Radium-223 and Docetaxel plus&#xD;
      prednisone in symptomatic bone-only metastatic castration-resistant prostate cancer (mCRPC)&#xD;
&#xD;
      Open-label, randomized phase II trial in patients with symptomatic bone-only metastatic&#xD;
      castration-resistant prostate cancer. Eligible patients are randomly assigned into two arms:&#xD;
&#xD;
        -  Arm A: radium-223 initially followed by docetaxel plus prednisone at the time of&#xD;
           progression (the second step is optional according to clinical evolution of disease)&#xD;
&#xD;
        -  Arm B: docetaxel plus prednisone initially followed by radium-223 at the time of&#xD;
           progression (the second step is optional according to clinical evolution of disease).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Randomized, multicentre phase II trial of the sequencing of Radium-223 and Docetaxel plus&#xD;
      prednisone in symptomatic bone-only metastatic castration-resistant prostate cancer (mCRPC)&#xD;
      Primary objective: To determine the effects of sequential treatment between radium-223 and&#xD;
      docetaxel on the percentage of symptomatic bone-only CRPC patients experiencing improvement&#xD;
      or worsening in health-related quality of life (HRQoL) Secondary objective: To compare&#xD;
      survival in patients treated with sequential therapy between radium-223 and docetaxel and to&#xD;
      identify predictive factors of Radium-223 for clinical outcome (progression free survival and&#xD;
      overall survival) in this patient population.&#xD;
&#xD;
      Study Treatment:&#xD;
&#xD;
      Radium-223: administered at the dose of 55 kBq per kg body weight, given at 4 week intervals&#xD;
      for 6 injections, by slow intravenous injection.&#xD;
&#xD;
      Docetaxel: administered at the dose of 75 mg/m2 by intravenous infusion over a period of 1&#xD;
      hour every 3 weeks for 10 cycles. It is associated with prednisone 5 mg orally twice daily&#xD;
      administered continuously.&#xD;
&#xD;
      Statistical methodology A responder analysis investigating treatment effects on percentage of&#xD;
      patients experiencing meaningful HRQoL improvement/worsening on treatment will be conducted.&#xD;
      When defining meaningful improvement/worsening, the upper limit of the minimally important&#xD;
      difference (MID) range will be used. The MIDs for FACT-P total score and subscales that will&#xD;
      be used in this study will be 10 and 3, respectively.&#xD;
&#xD;
      Patients experiencing a QoL increase &gt;=MID from baseline at week 12 will be considered&#xD;
      responders while patients experiencing a decrease in HRQoL score &gt;=MID at this time point&#xD;
      will be considered to have experienced worsening HRQoL.&#xD;
&#xD;
      According to primary endpoint, considering a type I error 0.10, type II error 0.20,&#xD;
      proportion of responder patients in the standard arm 0.10 and in the experimental arm of&#xD;
      0.40, a total of 70 patients (35 for each arm) will be enrolled in the study. Chi-square&#xD;
      tests will be used to test for an association between treatment and meaningful improvement&#xD;
      (i.e. responder) or worsening in HRQoL.&#xD;
&#xD;
      According to secondary endpoints, PFS, TPFS and OS will be estimated by the Kaplan-Meier&#xD;
      method. The treatment groups will be compared with a two-sided log rank test. All analyses&#xD;
      will be done in the intention-to-treat population. For translational studies, we will conduct&#xD;
      a prognostic and predictive factor analysis for time-to-event clinical outcomes using a&#xD;
      univariate Cox model; significant factors subsequently will be included in a multivariable&#xD;
      Cox regression model (cutoff p&lt;0•05).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 1, 2017</start_date>
  <completion_date type="Anticipated">July 2025</completion_date>
  <primary_completion_date type="Anticipated">July 2025</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>health-related quality of life (HRQoL) clinical benefit</measure>
    <time_frame>up to 36 months</time_frame>
    <description>HRQoL clinical benefit, according to the Functional Assessment of Cancer Therapy-Prostate (FACT-P)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>health-related quality of life (HRQoL ) clinical benefit</measure>
    <time_frame>up to 36 months</time_frame>
    <description>HRQoL clinical benefit, according to Brief Pain Inventory-Short Form questionnaire (BPI) for bone pain intensity.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>up to 36 months</time_frame>
    <description>PFS defined as the duration of time from randomization to time of progression or death, whichever occurred earlier</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total progression-free survival (TPFS)</measure>
    <time_frame>up to 36 months</time_frame>
    <description>TPFS defined as total PFS at the end of the therapeutic sequence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>up to 36 months</time_frame>
    <description>OS defined as the time from randomization to the date of death due to any cause or the last date the patient was known to be alive</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>toxic effects categorization for safety monitoring</measure>
    <time_frame>up to 36 months</time_frame>
    <description>evaluation of toxicity by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Identification of markers predictive to clinical outcome</measure>
    <time_frame>up to 36 months</time_frame>
    <description>Identification of markers predictive to clinical outcome including:&#xD;
translational studies of circulating tumor DNA and/or circulating tumor cells and/or circulating RNA&#xD;
serum chromogranin A and neuron specific enolase levels&#xD;
positron emission tomography (PET) with choline and/or new tracer</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">70</enrollment>
  <condition>Metastatic Castration-resistant Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Treatment Arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>radium-223 initially followed by docetaxel plus prednisone at the time of progression (PD)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Arm B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>docetaxel plus prednisone initially followed by radium-223 at the time of progression (PD)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Radium-223</intervention_name>
    <description>Radium-223: administered at the dose of 55 kBq per kg body weight, given at 4 week intervals for 6 injections, by slow intravenous injection</description>
    <arm_group_label>Treatment Arm A</arm_group_label>
    <arm_group_label>Treatment Arm B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Docetaxel</intervention_name>
    <description>Docetaxel: administered at the dose of 75 mg/m2 by intravenous infusion over a period of 1 hour every 3 weeks for 10 cycles. It is associated with prednisone 5 mg orally twice daily administered continuously.</description>
    <arm_group_label>Treatment Arm A</arm_group_label>
    <arm_group_label>Treatment Arm B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients must have histologically or cytologically confirmed adenocarcinoma of&#xD;
             prostate&#xD;
&#xD;
          2. Two or more bone metastases confirmed by bone scintigraphy within 4 weeks prior to&#xD;
             study entry&#xD;
&#xD;
          3. Symptomatic disease defined as regular use of opioid or non-opioid analgesic&#xD;
             medication or treatment with external beam radiation therapy within the previous 12&#xD;
             weeks for cancer-related bone pain&#xD;
&#xD;
          4. Known castration-resistant disease, defined according to the Prostate Cancer Clinical&#xD;
             Trials Working Group 3 (PCWG3) criteria as: castrate serum testosterone level: ≤50&#xD;
             ng/dL (≤1.7 nmol/L)&#xD;
&#xD;
          5. Subjects who have failed initial hormonal therapy, either by orchiectomy or by using a&#xD;
             gonadotropin-releasing hormone (GnRH) agonist in combination with an anti-androgen,&#xD;
             must first progress through antiandrogen withdrawal prior to being eligible. The&#xD;
             minimum timeframe to document failure of anti-androgen withdrawal will be four weeks&#xD;
&#xD;
          6. Progressive disease based on prostate-specific antigen (PSA) and/or radiographic PCWG3&#xD;
             criteria:&#xD;
&#xD;
               -  Serum PSA progression defined as two consecutive increases in PSA over a previous&#xD;
                  reference value within 6 months of first study treatment, each measurement at&#xD;
                  least one week apart. Serum PSA at screening ≥ 1ng/mL is the minimal starting&#xD;
                  value&#xD;
&#xD;
               -  or radiographic disease progression based on documented bone lesions by the&#xD;
                  appearance of two or more new lesions by bone scintigraphy&#xD;
&#xD;
          7. Patients who failed treatment with any Androgen deprivation therapy (ADT) abiraterone&#xD;
             and/or enzalutamide for CRPC that must be terminated at least 4 weeks before study&#xD;
             entry.&#xD;
&#xD;
          8. Male, aged ≥18 years.&#xD;
&#xD;
          9. Life expectancy of greater than 6 months.&#xD;
&#xD;
         10. Eastern Cooperative Oncology Group (ECOG) performance status≤2 .&#xD;
&#xD;
         11. Patients must have normal organ and marrow function as defined below:&#xD;
&#xD;
               -  leukocytes &gt;3,000 x 10 9/L&#xD;
&#xD;
               -  absolute neutrophil count &gt;1,500 x 10 9/L&#xD;
&#xD;
               -  platelets &gt;100,000 x 10 9/L&#xD;
&#xD;
               -  total bilirubin within normal institutional limits&#xD;
&#xD;
               -  aspartate aminotransferase (AST/SGOT)/alanine aminotransferase (ALT/SGPT) &lt;2.5 X&#xD;
                  institutional upper limit of normal&#xD;
&#xD;
               -  creatinine within normal institutional limits&#xD;
&#xD;
         12. Male patient and his female partner who is of childbearing potential must use 2&#xD;
             acceptable methods of birth control (1 of which must include a condom as a barrier&#xD;
             method of contraception) starting at screening and continuing throughout the study&#xD;
             period and for 6 months after the last dose of radium-223 or docetaxel, according to&#xD;
             guideline &quot;Recommendation related to contraception and pregnancy testing in clinical&#xD;
             trials&quot;, (2014_09_15 section 4.1) . Two acceptable methods of birth control thus&#xD;
             include condom (barrier method of contraception) and one of the following is required&#xD;
             (established use of oral, or injected or implanted hormonal method of contraception by&#xD;
             the female partner; placement of an intrauterine device (IUD) or intrauterine system&#xD;
             (IUS) by the female partner; additional barrier method like occlusive cap with&#xD;
             spermicidal foam/gel/film/cream/suppository in the female partner; tubal ligation in&#xD;
             the female partner; vasectomy or other procedure resulting in infertility (eg,&#xD;
             bilateral orchiectomy), for more than 6 months.&#xD;
&#xD;
         13. No evidence (within 5 years) of prior malignancies (except successfully treated basal&#xD;
             cell or squamous cell carcinoma of the skin).&#xD;
&#xD;
         14. Participant is willing and able to give informed consent for participation in the&#xD;
             study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients who have had previous chemotherapy.&#xD;
&#xD;
          2. Patients who have had radiotherapy within 4 weeks prior to entering the study.&#xD;
&#xD;
          3. Participation in another clinical trial with any investigational agents within 30 days&#xD;
             prior to study screening.&#xD;
&#xD;
          4. Concurrent use of other anticancer agents or treatments, with the following&#xD;
             exceptions: luteinizing hormone-releasing hormone (LHRH) agonists or antagonists,&#xD;
             denosumab or bisphosphonate (eg, zoledronic acid). Ongoing treatment should be kept at&#xD;
             a stable schedule; however, if medically required, a change of dose, compound, or both&#xD;
             is allowed.&#xD;
&#xD;
          5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements.&#xD;
&#xD;
          6. Patients who received systemic radiotherapy (e.g. samarium, strontium etc.) for the&#xD;
             treatment of bone metastases.&#xD;
&#xD;
          7. Patients who received blood transfusion or erythropoietin within the last 4 weeks&#xD;
             prior to start of study treatment.&#xD;
&#xD;
          8. Patients who received prior treatment with Radium-223.&#xD;
&#xD;
          9. Patients with malignant lymphadenopathy exceeding 3 cm in short-axis diameter, or&#xD;
             symptomatic nodal disease, i.e. scrotal, penile or leg edema.&#xD;
&#xD;
         10. Other primary tumor (other than CRPC) including hematological malignancy present&#xD;
             within the last 5 years (except non-melanoma skin cancer or low-grade superficial&#xD;
             bladder cancer).&#xD;
&#xD;
         11. Maintenance treatment with corticosteroids corresponding to a prednisolone or&#xD;
             prednisone dose above 10 mg/day. The dose must have been stable for at least 5 days.&#xD;
&#xD;
         12. Patients with imminent or established spinal cord compression based on clinical&#xD;
             findings and/or magnetic resonance imaging.&#xD;
&#xD;
         13. Positive test for HIV&#xD;
&#xD;
         14. Patients with active hepatitis B (defined as having a positive hepatitis B surface&#xD;
             antigen [HBsAg] test at screening) or hepatitis C&#xD;
&#xD;
               -  Patients with past hepatitis B virus (HBV) infection or resolved HBV infection&#xD;
                  (defined as having a negative HBsAg test and a positive antibody to hepatitis B&#xD;
                  core antigen (anti-HBc) antibody test) are eligible.&#xD;
&#xD;
               -  Patients positive for hepatitis C virus (HCV) antibody are eligible only if&#xD;
                  polymerase chain reaction (PCR) is negative for HCV RNA.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Vincenza Conteduca, MD</last_name>
    <role>Study Director</role>
    <affiliation>Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Via Maroncelli 40, 47014 Meldola, ITALY</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Oriana Nanni</last_name>
    <phone>+390543739266</phone>
    <email>oriana.nanni@irst.emr.it</email>
  </overall_contact>
  <location>
    <facility>
      <name>UO Oncologia Medica, IRST IRCCS</name>
      <address>
        <city>Meldola</city>
        <state>FC</state>
        <zip>47014</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ugo de Giorgi, MD</last_name>
      <phone>0543739100</phone>
      <email>ugo.degiorgi@irst.emr.it</email>
    </contact>
    <investigator>
      <last_name>Ugo De Giorgi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>U.O. Oncologia PO Vito Fazzi</name>
      <address>
        <city>Lecce</city>
        <state>LE</state>
        <zip>73100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vincenzo Emanuele Chiuri</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>IRCCS Istituto Clinico Humanitas</name>
      <address>
        <city>Rozzano</city>
        <state>Milano</state>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Paolo Andrea Zucali</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>UO Oncologia Medica, C.R.O.B. - I.R.C.C.S</name>
      <address>
        <city>Rionero in Vulture</city>
        <state>PZ</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Ospedale S. Chiara - UO Oncologia Medica</name>
      <address>
        <city>Trento</city>
        <state>TN</state>
        <zip>38122</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Orazio Caffo</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Oncologia Medica San Luigi Gonzaga</name>
      <address>
        <city>Orbassano</city>
        <state>TO</state>
        <zip>10043</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Consuelo Buttigliero</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ospedale Sacro Cuore &quot;Don Calabria&quot;</name>
      <address>
        <city>Negrar</city>
        <state>VR</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Stefania Gori, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Matteo Salgarello, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UO Oncologia medica, IRCCS Centro di Riferimento Oncologico di Aviano</name>
      <address>
        <city>Aviano</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Lucia Fratino, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Eugenio Borsatti, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>IO Oncologia Medica, Ospedale Regionale Bolzano - Az. Sanitaria Alto Adige</name>
      <address>
        <city>Bolzano</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Susanne Baier, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mohsen Farsad, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>IRCCS Ospedale Policlinico San Martino</name>
      <address>
        <city>Genova</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Giuseppe Fornarini</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Istituto Europeo di Oncologia</name>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Franco Nole</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>INT di Napoli Fondazione &quot;G. Pascale&quot;</name>
      <address>
        <city>Napoli</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>UO Oncologia Medica, Azienda Ospedaliera-Universitaria di Parma</name>
      <address>
        <city>Parma</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Donatello Gasparro, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Livia Ruffini, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UO Oncologia Medica, AOU PISANA - Ospedale Santa Chiara</name>
      <address>
        <city>Pisa</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Luca Galli, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Giuseppe Boni, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Arcispedale S. Maria Nuova/IRCCA di Reggio Emilia</name>
      <address>
        <city>Reggio Emilia</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>July 24, 2017</study_first_submitted>
  <study_first_submitted_qc>July 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 26, 2017</study_first_posted>
  <last_update_submitted>May 26, 2023</last_update_submitted>
  <last_update_submitted_qc>May 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>prostate cancer</keyword>
  <keyword>castration-resistant prostate cancer</keyword>
  <keyword>metastatic prostate cancer</keyword>
  <keyword>bone only metastatic prostate cancer</keyword>
  <keyword>radium-223</keyword>
  <keyword>Docetaxel</keyword>
  <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>Docetaxel</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03230734
org study id: IRST185.04
secondary id: 2016-004452-29
nct id: NCT03230734
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Randomized, multicentre phase II trial of the sequencing of Radium-223 and Docetaxel plus
      prednisone in symptomatic bone-only metastatic castration-resistant prostate cancer (mCRPC)

      Open-label, randomized phase II trial in patients with symptomatic bone-only metastatic
      castration-resistant prostate cancer. Eligible patients are randomly assigned into two arms:

        -  Arm A: radium-223 initially followed by docetaxel plus prednisone at the time of
           progression (the second step is optional according to clinical evolution of disease)

        -  Arm B: docetaxel plus prednisone initially followed by radium-223 at the time of
           progression (the second step is optional according to clinical evolution of disease).
Randomized, multicentre phase II trial of the sequencing of Radium-223 and Docetaxel plus
      prednisone in symptomatic bone-only metastatic castration-resistant prostate cancer (mCRPC)
      Primary objective: To determine the effects of sequential treatment between radium-223 and
      docetaxel on the percentage of symptomatic bone-only CRPC patients experiencing improvement
      or worsening in health-related quality of life (HRQoL) Secondary objective: To compare
      survival in patients treated with sequential therapy between radium-223 and docetaxel and to
      identify predictive factors of Radium-223 for clinical outcome (progression free survival and
      overall survival) in this patient population.

      Study Treatment:

      Radium-223: administered at the dose of 55 kBq per kg body weight, given at 4 week intervals
      for 6 injections, by slow intravenous injection.

      Docetaxel: administered at the dose of 75 mg/m2 by intravenous infusion over a period of 1
      hour every 3 weeks for 10 cycles. It is associated with prednisone 5 mg orally twice daily
      administered continuously.

      Statistical methodology A responder analysis investigating treatment effects on percentage of
      patients experiencing meaningful HRQoL improvement/worsening on treatment will be conducted.
      When defining meaningful improvement/worsening, the upper limit of the minimally important
      difference (MID) range will be used. The MIDs for FACT-P total score and subscales that will
      be used in this study will be 10 and 3, respectively.

      Patients experiencing a QoL increase >=MID from baseline at week 12 will be considered
      responders while patients experiencing a decrease in HRQoL score >=MID at this time point
      will be considered to have experienced worsening HRQoL.

      According to primary endpoint, considering a type I error 0.10, type II error 0.20,
      proportion of responder patients in the standard arm 0.10 and in the experimental arm of
      0.40, a total of 70 patients (35 for each arm) will be enrolled in the study. Chi-square
      tests will be used to test for an association between treatment and meaningful improvement
      (i.e. responder) or worsening in HRQoL.

      According to secondary endpoints, PFS, TPFS and OS will be estimated by the Kaplan-Meier
      method. The treatment groups will be compared with a two-sided log rank test. All analyses
      will be done in the intention-to-treat population. For translational studies, we will conduct
      a prognostic and predictive factor analysis for time-to-event clinical outcomes using a
      univariate Cox model; significant factors subsequently will be included in a multivariable
      Cox regression model (cutoff p<0•05).
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: health-related quality of life (HRQoL) clinical benefit
time frame: up to 36 months
description: HRQoL clinical benefit, according to the Functional Assessment of Cancer Therapy-Prostate (FACT-P)
measure: health-related quality of life (HRQoL ) clinical benefit
time frame: up to 36 months
description: HRQoL clinical benefit, according to Brief Pain Inventory-Short Form questionnaire (BPI) for bone pain intensity.
measure: Progression-free survival (PFS)
time frame: up to 36 months
description: PFS defined as the duration of time from randomization to time of progression or death, whichever occurred earlier
measure: Total progression-free survival (TPFS)
time frame: up to 36 months
description: TPFS defined as total PFS at the end of the therapeutic sequence
measure: Overall survival (OS)
time frame: up to 36 months
description: OS defined as the time from randomization to the date of death due to any cause or the last date the patient was known to be alive
measure: toxic effects categorization for safety monitoring
time frame: up to 36 months
description: evaluation of toxicity by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
measure: Identification of markers predictive to clinical outcome
time frame: up to 36 months
description: Identification of markers predictive to clinical outcome including:
translational studies of circulating tumor DNA and/or circulating tumor cells and/or circulating RNA
serum chromogranin A and neuron specific enolase levels
positron emission tomography (PET) with choline and/or new tracer
arm group label: Treatment Arm A
arm group type: Experimental
description: radium-223 initially followed by docetaxel plus prednisone at the time of progression (PD)
arm group label: Treatment Arm B
arm group type: Experimental
description: docetaxel plus prednisone initially followed by radium-223 at the time of progression (PD)
intervention type: Drug
intervention name: Radium-223
description: Radium-223: administered at the dose of 55 kBq per kg body weight, given at 4 week intervals for 6 injections, by slow intravenous injection
arm group label: Treatment Arm A
arm group label: Treatment Arm B
intervention type: Drug
intervention name: Docetaxel
description: Docetaxel: administered at the dose of 75 mg/m2 by intravenous infusion over a period of 1 hour every 3 weeks for 10 cycles. It is associated with prednisone 5 mg orally twice daily administered continuously.
arm group label: Treatment Arm A
arm group label: Treatment Arm B
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Vincenza Conteduca, MD
role: Study Director
affiliation: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Via Maroncelli 40, 47014 Meldola, ITALY
last name: Oriana Nanni
phone: +390543739266
email: oriana.nanni@irst.emr.it
facility: 
status: Recruiting
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status: Terminated
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status: Not yet recruiting
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status: Not yet recruiting
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status: Terminated
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status: Terminated
country: Italy
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Docetaxel