<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/NCT01734681</url>
  </required_header>
  <id_info>
    <org_study_id>G202-002</org_study_id>
    <nct_id>NCT01734681</nct_id>
  </id_info>
  <brief_title>Phase 2 Study of G-202 in Patients With Chemotherapy-Naïve Metastatic Castrate-Resistant Prostate Cancer</brief_title>
  <official_title>An Open-Label, Single-Arm, Phase 2 Study of G-202 in Patients With Chemotherapy-Naïve Metastatic Castrate-Resistant Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GenSpera, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GenSpera, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Prostate cancer that has returned after local treatment usually responds to hormone blocking&#xD;
      treatment, but most patients eventually experience disease progression. Further chemotherapy&#xD;
      does not normally lead to a cure or dramatic improvement in the disease and there is a need&#xD;
      to identify new drugs that are beneficial for these patients without unacceptable side&#xD;
      effects. Prodrug chemotherapy is an approach in which an inactive non-toxic agent is&#xD;
      administered to the patient and gets activated within the body at specific locations,&#xD;
      resulting in a higher concentration of the cytotoxic form at a tumour location whilst&#xD;
      avoiding general side effects. G-202 is an example of prodrug chemotherapy. It does not have&#xD;
      many general side effects because it is converted to a cell toxin only at the tumour or other&#xD;
      specific locations in the body. G-202 is activated by Prostate Specific Memory Antigen&#xD;
      (PSMA), a substance expressed by prostate cancer cells and in the blood vessels of most solid&#xD;
      tumours, but not by normal cells or blood vessels in normal tissue. It is believed that&#xD;
      activation of the prodrug G-202 will allow the drug to kill cancer cells, particularly&#xD;
      prostate cancer cells. This study will evaluate the activity and safety of G-202 in men with&#xD;
      castration-resistant prostate cancer (CRPC), which means the cancer has progressed after&#xD;
      hormone blocking treatment, but who have not yet received chemotherapy and who have no or&#xD;
      only a few symptoms from their CRPC. The study will evaluate clinical activity and safety of&#xD;
      G-202 administered on three consecutive days of a 28-day cycle.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients will undergo a screening period of up to 4 weeks. Patients who are deemed eligible&#xD;
      will be entered into the study and undergo treatment with G-202. G-202 will be administered&#xD;
      by intravenous infusion over one hour on Days 1, 2 and 3 of a 28-day treatment cycle. The&#xD;
      G-202 dose will be 40 mg/m2 on Day 1 and 66.8 mg/m2 on Days 2 and 3.&#xD;
&#xD;
      The primary objective of the study is to determine the percentage of patients with&#xD;
      chemotherapy-naïve metastatic castrate-resistant prostate cancer who do not have disease&#xD;
      progression (radiographic or clinical) after 24 weeks of treatment with G-202.&#xD;
&#xD;
      A two-stage study design will be used to evaluate the percentage of patients who do not have&#xD;
      disease progression after 24 weeks of treatment with G-202. If the percent of patients who&#xD;
      are progression-free at 24 weeks is at most 15%, then the clinical efficacy of G-202 in this&#xD;
      patient population will be considered unacceptably low. If, on the other hand, the percent of&#xD;
      patients who are progression-free at 24 weeks is at least 35%, this will be considered&#xD;
      sufficient evidence to consider further clinical investigation. The null hypothesis that the&#xD;
      percent of patients who are progression-free at 24 weeks is at most 15% will be tested&#xD;
      against the alternative hypothesis that the percent is greater than 15% at the one-sided 10%&#xD;
      significance level. In order to avoid a suspension in accrual awaiting interim analysis, a&#xD;
      two-stage study design for evaluating survival probabilities with continual accrual will be&#xD;
      used.&#xD;
&#xD;
      An interim analysis for futility will be conducted after 24 evaluable patients have been&#xD;
      accrued assuming that the time between accrual of the first patient and accrual of the 24th&#xD;
      patient is at least 8 months. If 24 patients are accrued in less than 8 months, accrual will&#xD;
      continue until the time period between the date of accrual of the first patient and the date&#xD;
      of accrual of the last patient is at least 8 months. If the trial is not terminated for&#xD;
      futility after the interim analysis, an additional 10 patients will be accrued for a total of&#xD;
      34 patients. The two-stage design minimizes the expected duration of accrual under the null&#xD;
      hypothesis.&#xD;
&#xD;
      For the interim analysis, any patient who discontinues participation for reasons other than&#xD;
      safety or disease progression before completing three full cycles and undergoing the 12-week&#xD;
      follow-up assessment will be replaced. Any replaced patient will be included in all study&#xD;
      analyses of the intent-to-treat and safety populations.&#xD;
&#xD;
      Safety will be assessed by the reporting of adverse events, vital signs and assessment of&#xD;
      findings on physical exam and routine laboratory determinations. The severity of adverse&#xD;
      events and laboratory findings will be assessed according to NCI Common Toxicity Criteria for&#xD;
      Adverse Effects (CTCAE) V4.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <start_date>May 2013</start_date>
  <completion_date type="Anticipated">January 2015</completion_date>
  <primary_completion_date type="Anticipated">January 2015</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of patients who are progression-free after 24 weeks of treatment with G-202</measure>
    <time_frame>24 weeks</time_frame>
    <description>Determine the percentage of patients with chemotherapy-naïve metastatic castrate-resistant prostate cancer who do not have disease progression (radiographic or clinical) after 24 weeks of treatment with G-202</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum prostatic specific antigen (PSA) change from baseline at any time</measure>
    <time_frame>Every 4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent change in PSA from baseline to 24 weeks</measure>
    <time_frame>24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to PSA progression</measure>
    <time_frame>Every 4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PSA Doubling time</measure>
    <time_frame>Every 4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best Objective Response</measure>
    <time_frame>Every 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Disease Progression</measure>
    <time_frame>Every 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>Every 12 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Prostate Cancer.</condition>
  <arm_group>
    <arm_group_label>Treatment with G-202</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>G-202 will be administered by intravenous infusion over one hour on Days 1, 2 and 3 of a 28-day treatment cycle. The G-202 dose will be 40 mg/m2 on Day 1 and 66.8 mg/m2 on Days 2 and 3.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>G-202</intervention_name>
    <arm_group_label>Treatment with G-202</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed prostate adenocarcinoma&#xD;
&#xD;
          -  Asymptomatic or minimally symptomatic&#xD;
&#xD;
          -  Radiographic metastatic or recurrent disease&#xD;
&#xD;
          -  Chemically- or surgically-castrated with disease progression&#xD;
&#xD;
          -  Castrate testosterone level &lt;50 ng/dL&#xD;
&#xD;
          -  Discontinued flutamide, bicalutamide and nilutamide&#xD;
&#xD;
          -  Absence of known brain metastases&#xD;
&#xD;
          -  Age ≥18 years&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group performance status ≤ 2&#xD;
&#xD;
          -  Estimated life expectancy ≥ 6 months&#xD;
&#xD;
          -  Adequate hematopoietic function as demonstrated by:&#xD;
&#xD;
               -  hemoglobin of ≥ 9.0 g/dL without need for sustained blood transfusions&#xD;
&#xD;
               -  platelet count ≥100,000 platelet/mm3 (100 x 109/L)&#xD;
&#xD;
               -  White Blood Cell (WBC) count ≥ 2.0 x109/L and Absolute Neutrophil Count (ANC)&#xD;
                  ≥1.5 x109/L&#xD;
&#xD;
          -  Adequate hepatobiliary function as demonstrated by:&#xD;
&#xD;
               -  Total bilirubin level ≤1.5 times the upper limit of normal (ULN), unless the&#xD;
                  patient has Gilbert's syndrome in which case the patient must have a total&#xD;
                  bilirubin level ≤ 2.5 x ULN&#xD;
&#xD;
               -  alanine aminotransferase (ALT) levels ≤ 2.5 x ULN&#xD;
&#xD;
          -  Adequate renal function as demonstrated by creatinine level ≤1.5 x ULN or creatinine&#xD;
             clearance (measured or calculated by Cockcroft-Gault formula) ≥ 50mL/min&#xD;
&#xD;
          -  Acceptable coagulation profile (PT or INR, PTT &lt; 1.5 x ULN)&#xD;
&#xD;
          -  If of reproductive capacity, willing to use an effective double barrier method of&#xD;
             birth control (i.e., latex condom, diaphragm, cervical cap, etc) during the study and&#xD;
             for 30 days after the last administration of G-202&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior chemotherapy&#xD;
&#xD;
          -  Other concurrent therapy for prostate cancer other than LHRH agonists or antagonists.&#xD;
&#xD;
          -  Treatment with therapeutic radionucleotides within 12 weeks of study entry&#xD;
&#xD;
          -  Radiation therapy &lt; 4 weeks before study entry&#xD;
&#xD;
          -  Documentation of keratosis follicularis&#xD;
&#xD;
          -  Pre-existing cardiac condition:&#xD;
&#xD;
          -  use of inhibitors or inducers of cytochrome (CYP3A4) iso-enzymes&#xD;
&#xD;
          -  Chronic use of opioids for cancer-related pain&#xD;
&#xD;
          -  Corrected QT interval &gt; 470 msec&#xD;
&#xD;
          -  Active uncontrolled infection, including known history of AIDS, hepatitis B or C&#xD;
&#xD;
          -  Proteinuria level &gt; +2 on urine analysis&#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>The University of Texas Health Science Center</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229-3900</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2013</verification_date>
  <study_first_submitted>November 19, 2012</study_first_submitted>
  <study_first_submitted_qc>November 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 28, 2012</study_first_posted>
  <last_update_submitted>February 16, 2014</last_update_submitted>
  <last_update_submitted_qc>February 16, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 19, 2014</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>
  <!-- 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/NCT01734681
org study id: G202-002
nct id: NCT01734681
lead sponsor: 
has dmc: No
Prostate cancer that has returned after local treatment usually responds to hormone blocking
      treatment, but most patients eventually experience disease progression. Further chemotherapy
      does not normally lead to a cure or dramatic improvement in the disease and there is a need
      to identify new drugs that are beneficial for these patients without unacceptable side
      effects. Prodrug chemotherapy is an approach in which an inactive non-toxic agent is
      administered to the patient and gets activated within the body at specific locations,
      resulting in a higher concentration of the cytotoxic form at a tumour location whilst
      avoiding general side effects. G-202 is an example of prodrug chemotherapy. It does not have
      many general side effects because it is converted to a cell toxin only at the tumour or other
      specific locations in the body. G-202 is activated by Prostate Specific Memory Antigen
      (PSMA), a substance expressed by prostate cancer cells and in the blood vessels of most solid
      tumours, but not by normal cells or blood vessels in normal tissue. It is believed that
      activation of the prodrug G-202 will allow the drug to kill cancer cells, particularly
      prostate cancer cells. This study will evaluate the activity and safety of G-202 in men with
      castration-resistant prostate cancer (CRPC), which means the cancer has progressed after
      hormone blocking treatment, but who have not yet received chemotherapy and who have no or
      only a few symptoms from their CRPC. The study will evaluate clinical activity and safety of
      G-202 administered on three consecutive days of a 28-day cycle.
Patients will undergo a screening period of up to 4 weeks. Patients who are deemed eligible
      will be entered into the study and undergo treatment with G-202. G-202 will be administered
      by intravenous infusion over one hour on Days 1, 2 and 3 of a 28-day treatment cycle. The
      G-202 dose will be 40 mg/m2 on Day 1 and 66.8 mg/m2 on Days 2 and 3.

      The primary objective of the study is to determine the percentage of patients with
      chemotherapy-naïve metastatic castrate-resistant prostate cancer who do not have disease
      progression (radiographic or clinical) after 24 weeks of treatment with G-202.

      A two-stage study design will be used to evaluate the percentage of patients who do not have
      disease progression after 24 weeks of treatment with G-202. If the percent of patients who
      are progression-free at 24 weeks is at most 15%, then the clinical efficacy of G-202 in this
      patient population will be considered unacceptably low. If, on the other hand, the percent of
      patients who are progression-free at 24 weeks is at least 35%, this will be considered
      sufficient evidence to consider further clinical investigation. The null hypothesis that the
      percent of patients who are progression-free at 24 weeks is at most 15% will be tested
      against the alternative hypothesis that the percent is greater than 15% at the one-sided 10%
      significance level. In order to avoid a suspension in accrual awaiting interim analysis, a
      two-stage study design for evaluating survival probabilities with continual accrual will be
      used.

      An interim analysis for futility will be conducted after 24 evaluable patients have been
      accrued assuming that the time between accrual of the first patient and accrual of the 24th
      patient is at least 8 months. If 24 patients are accrued in less than 8 months, accrual will
      continue until the time period between the date of accrual of the first patient and the date
      of accrual of the last patient is at least 8 months. If the trial is not terminated for
      futility after the interim analysis, an additional 10 patients will be accrued for a total of
      34 patients. The two-stage design minimizes the expected duration of accrual under the null
      hypothesis.

      For the interim analysis, any patient who discontinues participation for reasons other than
      safety or disease progression before completing three full cycles and undergoing the 12-week
      follow-up assessment will be replaced. Any replaced patient will be included in all study
      analyses of the intent-to-treat and safety populations.

      Safety will be assessed by the reporting of adverse events, vital signs and assessment of
      findings on physical exam and routine laboratory determinations. The severity of adverse
      events and laboratory findings will be assessed according to NCI Common Toxicity Criteria for
      Adverse Effects (CTCAE) V4.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of patients who are progression-free after 24 weeks of treatment with G-202
time frame: 24 weeks
description: Determine the percentage of patients with chemotherapy-naïve metastatic castrate-resistant prostate cancer who do not have disease progression (radiographic or clinical) after 24 weeks of treatment with G-202
measure: Maximum prostatic specific antigen (PSA) change from baseline at any time
time frame: Every 4 weeks
measure: Percent change in PSA from baseline to 24 weeks
time frame: 24 weeks
measure: Time to PSA progression
time frame: Every 4 weeks
measure: PSA Doubling time
time frame: Every 4 weeks
measure: Best Objective Response
time frame: Every 12 weeks
measure: Time to Disease Progression
time frame: Every 12 weeks
measure: Progression Free Survival
time frame: Every 12 weeks
arm group label: Treatment with G-202
arm group type: Experimental
description: G-202 will be administered by intravenous infusion over one hour on Days 1, 2 and 3 of a 28-day treatment cycle. The G-202 dose will be 40 mg/m2 on Day 1 and 66.8 mg/m2 on Days 2 and 3.
intervention type: Drug
intervention name: G-202
arm group label: Treatment with G-202
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