<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/NCT04486755</url>
  </required_header>
  <id_info>
    <org_study_id>HP-00091499</org_study_id>
    <nct_id>NCT04486755</nct_id>
  </id_info>
  <brief_title>Hypofractionated Accelerated Pelvic Nodal Radiotherapy (GCC 2048)</brief_title>
  <official_title>A Phase I Dose Escalation Study of Hypofractionated Accelerated Pelvic Nodal Radiotherapy Delivered With A Simultaneously Integrated Prostate Boost For Patients With Localized, Intermediate- And High-Risk Prostate Cancer (GCC 2048)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Maryland, Baltimore</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Maryland, Baltimore</source>
  <oversight_info>
    <has_dmc>Yes</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>
      A phase I trial to determine the safety of delivering three sequentially shorter RT schedules&#xD;
      (20, 16, and 12 fractions) of HypoFx pelvic nodal RT in combination with a HypoFx,&#xD;
      simultaneous integrated boost (SIB) to the prostate that have been designed to incrementally&#xD;
      increased the biological equivalent dose (BED) to prostate cancer, while maintaining a&#xD;
      constant BED to normal tissue toxicity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Outcomes for patients with unfavorable intermediate-risk and high-risk prostate cancer (PC)&#xD;
      have been historically poor and are now known to require multimodality treatment. A standard&#xD;
      non-surgical treatment option for patients with localized, intermediate and high-risk PC is&#xD;
      radiation therapy (RT) in combination with short- or long-term androgen deprivation therapy&#xD;
      (ADT).&#xD;
&#xD;
      The benefit of pelvic nodal RT in this setting is unclear, previous studies have been&#xD;
      equivocal. There is a growing body of evidence to demonstrate that use of hypofractionated&#xD;
      (HypoFx) RT may be a safe method for increasing the dose of RT, while also decreasing normal&#xD;
      tissue toxicity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 19, 2020</start_date>
  <completion_date type="Anticipated">August 2025</completion_date>
  <primary_completion_date type="Anticipated">August 2024</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>A modified 3+3 study design will be employed to determine the dose-fractionation schedule that results in less than 33% dose limiting toxicity. One de-escalation will be allowed if the initial dose-fractionation schedule results in too high a frequency of dose limiting toxicities. A total of 6 patients will be treated following the dose-fractionation schedule that is recommended for further study.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>HypoFx RT schedule that results in &lt;33% acute dose-limiting toxicity with accelerated, HypoFx pelvic nodal RT</measure>
    <time_frame>Within 90 days of completing RT</time_frame>
    <description>The frequency of all observed acute GI, GU, hematologic, and neurologic dose limiting toxicities by CTCAE v5 grade will be tabulated. DLT is defined as treatment-related: Grade ≥3 GI (small bowel or rectal) toxicity, Grade ≥3 GU toxicity, Grade ≥3 hematologic, Grade ≥3 neurologic toxicity, or any grade 5 treatment-related adverse events.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Frequency of acute and late GI, GU, hematologic, and neurologic toxicity for each dose cohort</measure>
    <time_frame>Acute (within 90 days completing RT), Late (occurring &gt; 90 days from treatment), 3-months, 6 months, 1-year and 2 years</time_frame>
    <description>The frequency of the maximum grade acute (within 90 days completing RT) and late (occurring &gt; 90 days from treatment) GI (small bowel and rectal), GU, hematologic, and neurologic toxicities at 3-months, 6 months, 1-year and 2 years for each dose cohort using National Cancer Institute Common Terminology Criteria v.5.0 (NCI CTCAE v5).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose volume histogram (DVH) parameters</measure>
    <time_frame>Within 90 days of completing RT</time_frame>
    <description>A dose-volume histogram is a histogram relating radiation dose to tissue volume in radiation therapy planning.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the duration of biochemical progression-free survival</measure>
    <time_frame>2 years after completing RT</time_frame>
    <description>The duration of bPFS will be measured from the end of RT until either PSA recurrence or death due to any cause and summarized for the expanded cohort of patients treated at the maximum total dose (MTD). PSA recurrence is defined by the Phoenix definition of biochemical failure (PSA nadir + 2 ng/mL).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Reported Outcomes (PROs) related to urinary and bowel function</measure>
    <time_frame>1 month after completion of treatment, every 3 months for year 1, and every 6 months during Year 2</time_frame>
    <description>Quality of life will be assessed with the validated Expanded Prostate Cancer Index Composite (EPIC) questionnaire.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Reported Outcomes (PROs) related to urinary function</measure>
    <time_frame>1 month after completion of treatment, every 3 months for year 1, and every 6 months during Year 2</time_frame>
    <description>The International Prostate System Score (IPSS) questionnaire will be used for urinary function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Reported Outcomes (PROs) related to urinary and bowel function</measure>
    <time_frame>1 month after completion of treatment, every 3 months for year 1, and every 6 months during Year 2</time_frame>
    <description>The PRO-CTCAE questionnaire measures patient-reported bowel, urinary and sexual function.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">18</enrollment>
  <condition>Prostate Cancer</condition>
  <condition>Prostate Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Dose Level 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose schedules were calculated to maintain similar BED for late normal tissue injury (α/β= 3.0 Gy), with an increased BED for PC (α/β= 1.5Gy). Patients be treated with 20 fractions. A total of 6 patients will be treated at the dose that is determined to be Maximum Tolerated Dose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Level 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose schedules were calculated to maintain similar BED for late normal tissue injury (α/β= 3.0 Gy), with an increased BED for PC (α/β= 1.5Gy). Patients be treated with 16 fractions. A total of 6 patients will be treated at the dose that is determined to be Maximum Tolerated Dose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Level 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose schedules were calculated to maintain similar BED for late normal tissue injury (α/β= 3.0 Gy), with an increased BED for PC (α/β= 1.5Gy). Patients be treated with 12 fractions. A total of 6 patients will be treated at the dose that is determined to be Maximum Tolerated Dose.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Hypofractionated Radiation Therapy</intervention_name>
    <description>All patients RT will be delivered utilizing pencil beam scanning proton therapy. Radiation treatment will be delivered 4 days per week.</description>
    <arm_group_label>Dose Level 1</arm_group_label>
    <arm_group_label>Dose Level 2</arm_group_label>
    <arm_group_label>Dose Level 3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient age is ≥ 18 years&#xD;
&#xD;
          2. Pathologically (histologically or cytologically) proven diagnosis of prostatic&#xD;
             adenocarcinoma within 180 days of registration.&#xD;
&#xD;
          3. Patient's with intermediate to high risk prostate cancer and must be recommended to&#xD;
             undergo pelvic as well as prostatic irradiation.&#xD;
&#xD;
          4. History/physical examination (to include at a minimum digital rectal examination of&#xD;
             the prostate and examination of the skeletal system and abdomen) within 90 days prior&#xD;
             to registration.&#xD;
&#xD;
          5. Clinically negative lymph nodes as established by imaging (pelvic ± abdominal CT or&#xD;
             MR), (but not by nodal sampling, or dissection) within 120 days prior to registration.&#xD;
&#xD;
             • Patients with lymph nodes equivocal or questionable by imaging are eligible if the&#xD;
             nodes are ≤ 1.5 cm.&#xD;
&#xD;
          6. No evidence of bone metastases (M0) on bone scan within 120 days prior to&#xD;
             registration.&#xD;
&#xD;
             • Equivocal bone scan findings are allowed if plain films (or CT or MRI) are negative&#xD;
             for metastasis.&#xD;
&#xD;
          7. Baseline serum PSA value performed within 12 weeks (90 days) prior to registration.&#xD;
&#xD;
          8. ECOG Performance Status 0-1&#xD;
&#xD;
          9. Patient must be able to provide study specific informed consent prior to study entry.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Evidence of distant metastases&#xD;
&#xD;
          2. Regional lymph node involvement&#xD;
&#xD;
          3. Previous radical surgery (prostatectomy), cryosurgery, or HIFU (High-intensity focused&#xD;
             ultrasound) for prostate cancer&#xD;
&#xD;
          4. Previous pelvic irradiation or prostate brachytherapy&#xD;
&#xD;
          5. Planned prostate brachytherapy boost&#xD;
&#xD;
          6. Previous or concurrent cytotoxic chemotherapy for prostate cancer&#xD;
&#xD;
          7. Severe acute or chronic medical or psychiatric condition or laboratory abnormality&#xD;
             that may increase the risk associated with study participation or study drug&#xD;
             administration, or may interfere with the interpretation of study results, and in the&#xD;
             judgment of the investigator would make the subject inappropriate for entry into this&#xD;
             study.&#xD;
&#xD;
          8. Patients are excluded if they have a history of autoimmune disease that, in the&#xD;
             opinion of the treating physician would be a contraindication to pelvic radiation&#xD;
             (e.g., active systemic lupus, progressive scleroderma)&#xD;
&#xD;
          9. Patients receiving full-dose anticoagulation or clopidogrel&#xD;
&#xD;
             • Patients taking 81 mg Aspirin po daily may are still eligible for the study&#xD;
&#xD;
         10. Patients with a history of prior small bowel ulceration&#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_contact>
    <last_name>Mark Mishra, MD</last_name>
    <phone>4103286080</phone>
    <email>mmishra@umm.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Acara Carter</last_name>
    <phone>410-369-5350</phone>
    <email>acara.carter@umm.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Maryland Proton Treatment Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mark Mishra, MD</last_name>
      <phone>410-328-6080</phone>
      <email>mmishra@umm.edu</email>
    </contact>
    <contact_backup>
      <last_name>Acara Carter</last_name>
      <phone>410-369-5350</phone>
      <email>acara.carter@umm.edu</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>July 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2020</study_first_posted>
  <last_update_submitted>May 2, 2023</last_update_submitted>
  <last_update_submitted_qc>May 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Maryland, Baltimore</investigator_affiliation>
    <investigator_full_name>Department of Radiation Oncology</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Prostate</keyword>
  <keyword>Hypofractionated Radiation Therapy</keyword>
  <keyword>Prostate Cancer</keyword>
  <keyword>Radiotherapy</keyword>
  <keyword>Proton Therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_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/NCT04486755
org study id: HP-00091499
nct id: NCT04486755
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A phase I trial to determine the safety of delivering three sequentially shorter RT schedules
      (20, 16, and 12 fractions) of HypoFx pelvic nodal RT in combination with a HypoFx,
      simultaneous integrated boost (SIB) to the prostate that have been designed to incrementally
      increased the biological equivalent dose (BED) to prostate cancer, while maintaining a
      constant BED to normal tissue toxicity.
Outcomes for patients with unfavorable intermediate-risk and high-risk prostate cancer (PC)
      have been historically poor and are now known to require multimodality treatment. A standard
      non-surgical treatment option for patients with localized, intermediate and high-risk PC is
      radiation therapy (RT) in combination with short- or long-term androgen deprivation therapy
      (ADT).

      The benefit of pelvic nodal RT in this setting is unclear, previous studies have been
      equivocal. There is a growing body of evidence to demonstrate that use of hypofractionated
      (HypoFx) RT may be a safe method for increasing the dose of RT, while also decreasing normal
      tissue toxicity.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: A modified 3+3 study design will be employed to determine the dose-fractionation schedule that results in less than 33% dose limiting toxicity. One de-escalation will be allowed if the initial dose-fractionation schedule results in too high a frequency of dose limiting toxicities. A total of 6 patients will be treated following the dose-fractionation schedule that is recommended for further study.
primary purpose: Treatment
masking: None (Open Label)
measure: HypoFx RT schedule that results in <33% acute dose-limiting toxicity with accelerated, HypoFx pelvic nodal RT
time frame: Within 90 days of completing RT
description: The frequency of all observed acute GI, GU, hematologic, and neurologic dose limiting toxicities by CTCAE v5 grade will be tabulated. DLT is defined as treatment-related: Grade ≥3 GI (small bowel or rectal) toxicity, Grade ≥3 GU toxicity, Grade ≥3 hematologic, Grade ≥3 neurologic toxicity, or any grade 5 treatment-related adverse events.
measure: Frequency of acute and late GI, GU, hematologic, and neurologic toxicity for each dose cohort
time frame: Acute (within 90 days completing RT), Late (occurring > 90 days from treatment), 3-months, 6 months, 1-year and 2 years
description: The frequency of the maximum grade acute (within 90 days completing RT) and late (occurring > 90 days from treatment) GI (small bowel and rectal), GU, hematologic, and neurologic toxicities at 3-months, 6 months, 1-year and 2 years for each dose cohort using National Cancer Institute Common Terminology Criteria v.5.0 (NCI CTCAE v5).
measure: Dose volume histogram (DVH) parameters
time frame: Within 90 days of completing RT
description: A dose-volume histogram is a histogram relating radiation dose to tissue volume in radiation therapy planning.
measure: Evaluate the duration of biochemical progression-free survival
time frame: 2 years after completing RT
description: The duration of bPFS will be measured from the end of RT until either PSA recurrence or death due to any cause and summarized for the expanded cohort of patients treated at the maximum total dose (MTD). PSA recurrence is defined by the Phoenix definition of biochemical failure (PSA nadir + 2 ng/mL).
measure: Patient Reported Outcomes (PROs) related to urinary and bowel function
time frame: 1 month after completion of treatment, every 3 months for year 1, and every 6 months during Year 2
description: Quality of life will be assessed with the validated Expanded Prostate Cancer Index Composite (EPIC) questionnaire.
measure: Patient Reported Outcomes (PROs) related to urinary function
time frame: 1 month after completion of treatment, every 3 months for year 1, and every 6 months during Year 2
description: The International Prostate System Score (IPSS) questionnaire will be used for urinary function.
measure: Patient Reported Outcomes (PROs) related to urinary and bowel function
time frame: 1 month after completion of treatment, every 3 months for year 1, and every 6 months during Year 2
description: The PRO-CTCAE questionnaire measures patient-reported bowel, urinary and sexual function.
arm group label: Dose Level 1
arm group type: Experimental
description: Dose schedules were calculated to maintain similar BED for late normal tissue injury (α/β= 3.0 Gy), with an increased BED for PC (α/β= 1.5Gy). Patients be treated with 20 fractions. A total of 6 patients will be treated at the dose that is determined to be Maximum Tolerated Dose.
arm group label: Dose Level 2
arm group type: Experimental
description: Dose schedules were calculated to maintain similar BED for late normal tissue injury (α/β= 3.0 Gy), with an increased BED for PC (α/β= 1.5Gy). Patients be treated with 16 fractions. A total of 6 patients will be treated at the dose that is determined to be Maximum Tolerated Dose.
arm group label: Dose Level 3
arm group type: Experimental
description: Dose schedules were calculated to maintain similar BED for late normal tissue injury (α/β= 3.0 Gy), with an increased BED for PC (α/β= 1.5Gy). Patients be treated with 12 fractions. A total of 6 patients will be treated at the dose that is determined to be Maximum Tolerated Dose.
intervention type: Radiation
intervention name: Hypofractionated Radiation Therapy
description: All patients RT will be delivered utilizing pencil beam scanning proton therapy. Radiation treatment will be delivered 4 days per week.
arm group label: Dose Level 1
arm group label: Dose Level 2
arm group label: Dose Level 3
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mark Mishra, MD
phone: 4103286080
email: mmishra@umm.edu
last name: Acara Carter
phone: 410-369-5350
email: acara.carter@umm.edu
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Maryland, Baltimore
investigator full name: Department of Radiation Oncology
investigator title: Principal Investigator
mesh term: Prostatic Neoplasms
sharing ipd: No