<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/NCT03827616</url>
  </required_header>
  <id_info>
    <org_study_id>prostata116</org_study_id>
    <nct_id>NCT03827616</nct_id>
  </id_info>
  <brief_title>Moderately Hypofractionated Radiotherapy for Prostate Cancer.</brief_title>
  <official_title>A Prospective Randomized Phase II Clinical Trial of Moderately Hypofractionated Radiotherapy (70 Gy in 28 Fractions vs 60 Gy in 20 Fractions) Using Helical Tomotherapy.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tatarstan Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tatarstan Cancer Center</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Radiation therapy is one of the standard treatments for men with prostate cancer. Moderately&#xD;
      hypofractionated radiotherapy has been established to be equivalent to standard fractionated&#xD;
      radiotherapy in several large randomized clinical trials, however different hypofractionated&#xD;
      regimens have been used in these studies. The two most common hypofractionated regimens are&#xD;
      70 Gy in 28 fractions and 60 Gy in 20 fractions, both are considered standard of care,&#xD;
      however it is not unknown which regimen is better in terms of effectiveness and toxicity. The&#xD;
      aim of this randomized controlled clinical trial is to compare the two hypofractionated&#xD;
      radiotherapy regimens using Helical Tomotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OBJECTIVES:&#xD;
&#xD;
      Primary&#xD;
&#xD;
      Compare the biochemical relapse free survival (DFS) of patients with prostate cancer treated&#xD;
      with hypofractionated regimens 70 Gy in 28 fractions and 60 Gy in 20 fractions&#xD;
      intensity-modulated radiotherapy (IMRT) using helical Tomotherapy.&#xD;
&#xD;
      Secondary&#xD;
&#xD;
      Compare time to local progression, freedom from biochemical recurrence, and disease-specific&#xD;
      and overall survival of patients treated with these regimens.&#xD;
&#xD;
      Determine the incidence of gastrointestinal and genitourinary toxic effects in patients&#xD;
      treated with these regimens.&#xD;
&#xD;
      OUTLINE: This is a randomized study. Patients are stratified according to TNM ( T1-3N0M0),&#xD;
      Gleason score (6,7 (3+4), 7(4+3), 8). Before radiotherapy patients receive hormone therapy&#xD;
      from 3 months to 6 months. Patients are randomized to 1 of 2 treatment arms.&#xD;
&#xD;
      Arm 1 hypofractionated dosing 28 fractions x 2,5 Gy over 38 days (prostate 28 x 2,5Gy - 70Gy,&#xD;
      seminal vesicles 28 x 2Gy - 56 Gy, node lympaticus ( if Rouch formula&gt; 15% or N1) 28 x 1,8 Gy&#xD;
      - 50,4 Gy).&#xD;
&#xD;
      Arm II hypofractionated dosing 20 fractions x 3 Gy over 26day (prostate 20 x 3Gy - 60Gy,&#xD;
      seminal vesicles 20 x 2,5Gy - 50 Gy, node lympaticus ( if if Rouch formula&gt; 15% or N1 ) 20 x&#xD;
      2,2 Gy - 44 Gy).&#xD;
&#xD;
      After completion of study treatment, patients are followed every 3 months for 2 years, every&#xD;
      6 months for 3 years, and then annually thereafter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">January 25, 2019</start_date>
  <completion_date type="Anticipated">February 1, 2030</completion_date>
  <primary_completion_date type="Anticipated">February 1, 2029</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Biochemical Relapse Free Survival Rate</measure>
    <time_frame>Analysis occurs after all patients have been followed for five year.</time_frame>
    <description>Determine what regime of hypofractionation will be the best 5-10 year biochemical disease free survival. Compare the results of hypofractional regimes (60Gy in 20 farctions; 70 Gy in 28 farctions).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Biochemical Relapse Free Survival Rate</measure>
    <time_frame>Analysis occurs after all patients have been followed for ten year.</time_frame>
    <description>Determine what regime of hypofractionation will be the best 5-10 year biochemical disease free survival. Compare the results of hypofractional regimes (60Gy in 20 farctions; 70 Gy in 28 farctions).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Five year Local Progression Rate</measure>
    <time_frame>Analysis occurs after all patients have been followed for five year.</time_frame>
    <description>Clinical criteria for local recurrence are progression (increase in palpable abnormality) at any time, failure of regression of the palpable tumor by 2 years, and redevelopment of a palpable abnormality after complete disappearance of previous abnormalities. Histologic criteria for local recurrence are presence of prostatic carcinoma upon biopsy and positive biopsy of the palpably normal prostate more than 2 years after the start of treatment. The arms were not statistically compared because of an insufficient number of events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ten year Local Progression Rate</measure>
    <time_frame>Analysis occurs after all patients have been followed for ten year.</time_frame>
    <description>Clinical criteria for local recurrence are progression (increase in palpable abnormality) at any time, failure of regression of the palpable tumor by 2 years, and redevelopment of a palpable abnormality after complete disappearance of previous abnormalities. Histologic criteria for local recurrence are presence of prostatic carcinoma upon biopsy and positive biopsy of the palpably normal prostate more than 2 years after the start of treatment. The arms were not statistically compared because of an insufficient number of events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Five year Overall Survival Rate</measure>
    <time_frame>Analysis occurs after all patients have been followed for five year.</time_frame>
    <description>Five-year rates Kaplan-Meier estimates. Overall survival (OS) was measured from study entry until the date of death. Patients still alive at the time of analysis were censored at the date of last follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ten year Overall Survival Rate</measure>
    <time_frame>Analysis occurs after all patients have been followed for ten year.</time_frame>
    <description>Five-year rates Kaplan-Meier estimates. Overall survival (OS) was measured from study entry until the date of death. Patients still alive at the time of analysis were censored at the date of last follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of Patients With GU and GI Acute and Late Toxicity</measure>
    <time_frame>Acute toxicity is measured from start of treatment to 90 days from the completion of treatment. Late toxicity is defined as toxicity occuring after 90 days from completion of treatment. Analysis occured at the time of the primary endpoint analysis.</time_frame>
    <description>The frequency of GU and GI adverse events as defined and graded according to the National Cancer Institute СTCAE v4 were compared between treatment arms. Acute toxicity was defined as any toxicity beginning within 90 days of completion of RT, and late toxicity was defined as any toxicity beginning more than 90 days after the completion of RT. Acute and late GU and GI toxicity rates were tabulated and reported in two ways: dichotomized as &lt; grade 2 vs ≥ grade 2, and dichotomized as &lt; grade 3 vs ≥ grade 3. Higher grade indicates more severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Five year Quality of life measured with EQ5D.</measure>
    <time_frame>Analysis occurs after all patients have been followed for five year.</time_frame>
    <description>Compare quality of life of patients in 2 groups using the scale EQ5D (European Quality of Life Questionnaire).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Five year Quality of life measured with EPIС СP.</measure>
    <time_frame>Analysis occurs after all patients have been followed for five year.</time_frame>
    <description>Compare quality of life of patients in 2 groups using the scale EPIС СP (Expanded Prostate Cancer Index Composite for Clinical Practice).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ten year Quality of life measured with EQ5D.</measure>
    <time_frame>Analysis occurs after all patients have been followed for ten year.</time_frame>
    <description>.Compare quality of life of patients in 2 groups using the scale EQ5D (European Quality of Life Questionnaire).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ten year Quality of life measured with EPIС СP.</measure>
    <time_frame>Analysis occurs after all patients have been followed for ten year.</time_frame>
    <description>Compare quality of life of patients in 2 groups using the scale EPIС СP (Expanded Prostate Cancer Index Composite for Clinical Practice)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Prostatic Neoplasms</condition>
  <condition>Genital Neoplasms</condition>
  <arm_group>
    <arm_group_label>2,5 Gy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>hypofractionated dosing 28 fractions x 2,5 Gy over 38 days (prostate 28 x 2,5Gy - 70Gy, seminal vesicles 28 x 2Gy - 56 Gy, node lympaticus ( if Rouch formula&gt; 15% or N1) 28 x 1,8 Gy - 50,4 Gy).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>3 Gy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>hypofractionated dosing 20 fractions x 3 Gy over 26day (prostate 20 x 3Gy - 60Gy, seminal vesicles 20 x 2,5Gy - 50 Gy, node lympaticus ( if if Rouch formula&gt; 15% or N1 ) 20 x 2,2 Gy - 44 Gy).</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Hypofractionated IMRT using helical Tomotherapy.</intervention_name>
    <description>70 Gy in 28 fractions intensity-modulated radiotherapy (IMRT)</description>
    <arm_group_label>2,5 Gy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Hypofractionated IMRT using helical Tomotherapy.</intervention_name>
    <description>60 Gy in 20 fractions intensity-modulated radiotherapy (IMRT) using helical Tomotherapy.</description>
    <arm_group_label>3 Gy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
        1. Histologically confirmed adenocarcinoma of the prostate. 2 The presence of the following&#xD;
        studies: TRUS of the prostate gland, pelvis MRI, OSG.&#xD;
&#xD;
        3 Histological evaluation of prostate biopsy with assignment of the Gleason index.&#xD;
&#xD;
        4 Clinical stage T1-3N0M0 (AJCC 7th edition). 5 ECOG performance status 0-1 6 Age limit 18&#xD;
        years. 7 Patient consent to participate in a clinical study.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Prior or concurrent lymphomatous/hematogenous malignancy or other invasive malignancy&#xD;
             except nonmelanomatous skin cancer or any other cancer for which the patient has been&#xD;
             continually disease-free for ≥ 5 years (e.g., carcinoma in situ of the bladder or oral&#xD;
             cavity)&#xD;
&#xD;
          2. Distatnt metastases.&#xD;
&#xD;
          3. Metastases in the lymph nodes of prostate cancer.&#xD;
&#xD;
          4. Radical prostatectomy or cryodestruction of the prostate gland in history.&#xD;
&#xD;
          5. Radiation of a small pelvis in the anamnesis. Bilateral orchectomy history.&#xD;
&#xD;
          6. Unstable angina and/or congestive heart failure requiring hospitalization within the&#xD;
             past 6 months, transmural myocardial infarction within the past 6 months, acute&#xD;
             bacterial or fungal infection requiring IV antibiotics, chronic obstructive pulmonary&#xD;
             disease exacerbation or other respiratory illness requiring hospitalization or&#xD;
             precluding study treatment, hepatic insufficiency resulting in clinical jaundice&#xD;
             and/or coagulation defects.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Tatarstan Cancer Cente</name>
      <address>
        <city>Kazan</city>
        <state>Tatarstan</state>
        <zip>420029</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>January 30, 2019</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 1, 2019</study_first_posted>
  <last_update_submitted>February 8, 2019</last_update_submitted>
  <last_update_submitted_qc>February 8, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 12, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Prostate cancer</keyword>
  <keyword>Radiation therapy</keyword>
  <keyword>Hypofractionated radiotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 25, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/16/NCT03827616/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 25, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/16/NCT03827616/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03827616
org study id: prostata116
nct id: NCT03827616
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Radiation therapy is one of the standard treatments for men with prostate cancer. Moderately
      hypofractionated radiotherapy has been established to be equivalent to standard fractionated
      radiotherapy in several large randomized clinical trials, however different hypofractionated
      regimens have been used in these studies. The two most common hypofractionated regimens are
      70 Gy in 28 fractions and 60 Gy in 20 fractions, both are considered standard of care,
      however it is not unknown which regimen is better in terms of effectiveness and toxicity. The
      aim of this randomized controlled clinical trial is to compare the two hypofractionated
      radiotherapy regimens using Helical Tomotherapy.
OBJECTIVES:

      Primary

      Compare the biochemical relapse free survival (DFS) of patients with prostate cancer treated
      with hypofractionated regimens 70 Gy in 28 fractions and 60 Gy in 20 fractions
      intensity-modulated radiotherapy (IMRT) using helical Tomotherapy.

      Secondary

      Compare time to local progression, freedom from biochemical recurrence, and disease-specific
      and overall survival of patients treated with these regimens.

      Determine the incidence of gastrointestinal and genitourinary toxic effects in patients
      treated with these regimens.

      OUTLINE: This is a randomized study. Patients are stratified according to TNM ( T1-3N0M0),
      Gleason score (6,7 (3+4), 7(4+3), 8). Before radiotherapy patients receive hormone therapy
      from 3 months to 6 months. Patients are randomized to 1 of 2 treatment arms.

      Arm 1 hypofractionated dosing 28 fractions x 2,5 Gy over 38 days (prostate 28 x 2,5Gy - 70Gy,
      seminal vesicles 28 x 2Gy - 56 Gy, node lympaticus ( if Rouch formula> 15% or N1) 28 x 1,8 Gy
      - 50,4 Gy).

      Arm II hypofractionated dosing 20 fractions x 3 Gy over 26day (prostate 20 x 3Gy - 60Gy,
      seminal vesicles 20 x 2,5Gy - 50 Gy, node lympaticus ( if if Rouch formula> 15% or N1 ) 20 x
      2,2 Gy - 44 Gy).

      After completion of study treatment, patients are followed every 3 months for 2 years, every
      6 months for 3 years, and then annually thereafter.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Biochemical Relapse Free Survival Rate
time frame: Analysis occurs after all patients have been followed for five year.
description: Determine what regime of hypofractionation will be the best 5-10 year biochemical disease free survival. Compare the results of hypofractional regimes (60Gy in 20 farctions; 70 Gy in 28 farctions).
measure: Biochemical Relapse Free Survival Rate
time frame: Analysis occurs after all patients have been followed for ten year.
description: Determine what regime of hypofractionation will be the best 5-10 year biochemical disease free survival. Compare the results of hypofractional regimes (60Gy in 20 farctions; 70 Gy in 28 farctions).
measure: Five year Local Progression Rate
time frame: Analysis occurs after all patients have been followed for five year.
description: Clinical criteria for local recurrence are progression (increase in palpable abnormality) at any time, failure of regression of the palpable tumor by 2 years, and redevelopment of a palpable abnormality after complete disappearance of previous abnormalities. Histologic criteria for local recurrence are presence of prostatic carcinoma upon biopsy and positive biopsy of the palpably normal prostate more than 2 years after the start of treatment. The arms were not statistically compared because of an insufficient number of events.
measure: Ten year Local Progression Rate
time frame: Analysis occurs after all patients have been followed for ten year.
description: Clinical criteria for local recurrence are progression (increase in palpable abnormality) at any time, failure of regression of the palpable tumor by 2 years, and redevelopment of a palpable abnormality after complete disappearance of previous abnormalities. Histologic criteria for local recurrence are presence of prostatic carcinoma upon biopsy and positive biopsy of the palpably normal prostate more than 2 years after the start of treatment. The arms were not statistically compared because of an insufficient number of events.
measure: Five year Overall Survival Rate
time frame: Analysis occurs after all patients have been followed for five year.
description: Five-year rates Kaplan-Meier estimates. Overall survival (OS) was measured from study entry until the date of death. Patients still alive at the time of analysis were censored at the date of last follow-up
measure: Ten year Overall Survival Rate
time frame: Analysis occurs after all patients have been followed for ten year.
description: Five-year rates Kaplan-Meier estimates. Overall survival (OS) was measured from study entry until the date of death. Patients still alive at the time of analysis were censored at the date of last follow-up
measure: Frequency of Patients With GU and GI Acute and Late Toxicity
time frame: Acute toxicity is measured from start of treatment to 90 days from the completion of treatment. Late toxicity is defined as toxicity occuring after 90 days from completion of treatment. Analysis occured at the time of the primary endpoint analysis.
description: The frequency of GU and GI adverse events as defined and graded according to the National Cancer Institute СTCAE v4 were compared between treatment arms. Acute toxicity was defined as any toxicity beginning within 90 days of completion of RT, and late toxicity was defined as any toxicity beginning more than 90 days after the completion of RT. Acute and late GU and GI toxicity rates were tabulated and reported in two ways: dichotomized as < grade 2 vs ≥ grade 2, and dichotomized as < grade 3 vs ≥ grade 3. Higher grade indicates more severity.
measure: Five year Quality of life measured with EQ5D.
time frame: Analysis occurs after all patients have been followed for five year.
description: Compare quality of life of patients in 2 groups using the scale EQ5D (European Quality of Life Questionnaire).
measure: Five year Quality of life measured with EPIС СP.
time frame: Analysis occurs after all patients have been followed for five year.
description: Compare quality of life of patients in 2 groups using the scale EPIС СP (Expanded Prostate Cancer Index Composite for Clinical Practice).
measure: Ten year Quality of life measured with EQ5D.
time frame: Analysis occurs after all patients have been followed for ten year.
description: .Compare quality of life of patients in 2 groups using the scale EQ5D (European Quality of Life Questionnaire).
measure: Ten year Quality of life measured with EPIС СP.
time frame: Analysis occurs after all patients have been followed for ten year.
description: Compare quality of life of patients in 2 groups using the scale EPIС СP (Expanded Prostate Cancer Index Composite for Clinical Practice)
arm group label: 2,5 Gy
arm group type: Active Comparator
description: hypofractionated dosing 28 fractions x 2,5 Gy over 38 days (prostate 28 x 2,5Gy - 70Gy, seminal vesicles 28 x 2Gy - 56 Gy, node lympaticus ( if Rouch formula> 15% or N1) 28 x 1,8 Gy - 50,4 Gy).
arm group label: 3 Gy
arm group type: Active Comparator
description: hypofractionated dosing 20 fractions x 3 Gy over 26day (prostate 20 x 3Gy - 60Gy, seminal vesicles 20 x 2,5Gy - 50 Gy, node lympaticus ( if if Rouch formula> 15% or N1 ) 20 x 2,2 Gy - 44 Gy).
intervention type: Radiation
intervention name: Hypofractionated IMRT using helical Tomotherapy.
description: 70 Gy in 28 fractions intensity-modulated radiotherapy (IMRT)
arm group label: 2,5 Gy
intervention type: Radiation
intervention name: Hypofractionated IMRT using helical Tomotherapy.
description: 60 Gy in 20 fractions intensity-modulated radiotherapy (IMRT) using helical Tomotherapy.
arm group label: 3 Gy
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
facility: 
country: Russian Federation
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Prostatic Neoplasms
sharing ipd: Undecided
provided document: 
provided document: 