<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/NCT01685489</url>
  </required_header>
  <id_info>
    <org_study_id>1U19AT006028-01A1</org_study_id>
    <nct_id>NCT01685489</nct_id>
  </id_info>
  <brief_title>A Phase 1b Dose Escalation Trial of PSK®/Placebo With Docetaxel to Treat Metastatic Castration-resistant Prostate Cancer</brief_title>
  <official_title>A Phase 1b Dose Escalation Trial of PSK®/Placebo With Docetaxel to Treat Metastatic Castration-resistant Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bastyr University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fred Hutchinson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Bastyr University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase 1b study that follows a 3+3 dose escalation design and consists of a 21-day&#xD;
      lead-in period of oral Polysaccharide Krestin (PSK)/placebo (study drug) alone followed by&#xD;
      the addition to study drug of standard intravenous docetaxel at 75 mg/m2 every 3 weeks for&#xD;
      three cycles. Study drug will be discontinued on day 15 of the third docetaxel cycle to allow&#xD;
      for a 7-day washout period before the fourth dose of docetaxel. Pharmacokinetic (PK) analysis&#xD;
      of docetaxel will be conducted during docetaxel cycle 1 (combination therapy) and cycle 4&#xD;
      (docetaxel alone). Serum for future PSK PK analysis will be collected on days 1, 3, and 15 of&#xD;
      PSK/placebo lead-in and during cycles 1 and 4.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    funding sequestered&#xD;
  </why_stopped>
  <start_date>May 2013</start_date>
  <phase>Phase 1</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Determine tolerability dose of PSK alone and in combination with docetaxel</measure>
    <time_frame>42 days</time_frame>
    <description>Adverse events are graded to determine a dose limiting toxicity of PSK during the lead-in PSK alone and during the docetaxel treatment in combination with PSK.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Determine maximum tolerated dose and recommended phase 2 dose of PSK in combination with docetaxel</measure>
    <time_frame>106 days</time_frame>
    <description>When the maximum tolerated dose is determined, a total of 15 patients will be treated with the recommended phase 2 dose with the combination of docetaxel chemotherapy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of docetaxel when combined with oral PSK</measure>
    <time_frame>106 days</time_frame>
    <description>The plasma docetaxel levels are analyzed at eight time points during the cycle 1 of standard intravenous docetaxel at 75 mg/m2 with oral PSK/Placebo. After the seven-day washout of PSK/placebo at the cycle 3, the plasma docetaxel levels are analyzed again at eight time points during the cycle 4 of docetaxel treatment without PSK/Placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of oral PSK dosing and in combination with docetaxel</measure>
    <time_frame>106 days</time_frame>
    <description>The serum PSK levels are analyzed at two time points during the lead-in cycle and eight time points during the cycle 1 of standard intravenous docetaxel at 75 mg/m2 with oral PSK/Placebo. After the seven-day washout of PSK/placebo at the cycle 3, the plasma docetaxel levels are analyzed again at eight time points during the cycle 4 of docetaxel treatment without PSK/Placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunological laboratory analysis</measure>
    <time_frame>106 days</time_frame>
    <description>Natural Killer (NK) cell functional activity, distributions of NK, B, and T cells, and IFN-gamma and TNF-alpha production capacity are analyzed and compared to those of the placebo group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical tumor markers</measure>
    <time_frame>106 days</time_frame>
    <description>Circulating tumor cell (CTC) and prostate specific antigen (PSA) levels are compared to that of the placebo group during the oral PSK lead-in period and during the combination therapy with docetaxel and PSK.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prostatic acid phosphatase</measure>
    <time_frame>106</time_frame>
    <description>The serum level of prostatic acid phosphatase levels are compared to that of the placebo group during the oral PSK lead-in period and during the combination therapy with docetaxel and PSK.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Prostatic Neoplasms</condition>
  <arm_group>
    <arm_group_label>Docetaxel, PSK®</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A 21-day lead-in oral PSK alone is followed by the addition of standard intravenous docetaxel at 75 mg/m2 evey 3 weeks for three cycles. After the third dose of docetaxel, study drug will be discontinued on day 14 to allow for a 7-day washout period before a fourth dose of docetaxel is administered.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Docetaxel, Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>A 21-day lead-in oral placebo alone is followed by the addition of standard intravenous docetaxel at 75 mg/m2 every 3 weeks for three cycles. After the third dose of docetaxel, the placebo will be discontinued on day 14 to allow for a 7-day washout period before a fourth dose of docetaxel is administered.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Docetaxel, PSK®</intervention_name>
    <arm_group_label>Docetaxel, PSK®</arm_group_label>
    <other_name>Polysaccharide-K</other_name>
    <other_name>Krestin</other_name>
    <other_name>Polysaccharide-Kureha</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Docetaxel, Placebo</intervention_name>
    <arm_group_label>Docetaxel, Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male patients 18 years or older&#xD;
&#xD;
          -  Histologically confirmed diagnosis of adenocarcinoma of the prostate&#xD;
&#xD;
          -  Evidence of metastatic disease by standard imaging studies (bone scan, Computerized&#xD;
             Tomography Scan (CT) or Magnetic Resonance Imaging (MRI))&#xD;
&#xD;
          -  Testosterone levels &lt;50 ng/dL&#xD;
&#xD;
          -  Confirmed progressive disease defined by one or more of the following:&#xD;
&#xD;
               -  an increase in PSA, &gt; 2ng/dL x 2 or more values at least 1 week apart in the&#xD;
                  setting of metastatic disease&#xD;
&#xD;
               -  appearance of new bone lesions on bone scan&#xD;
&#xD;
               -  progression of soft tissue lesion defined by the Response Evaluation Criteria In&#xD;
                  Solid Tumors [RECIST] 1.1 criteria&#xD;
&#xD;
          -  Concurrent use of an agent for testosterone suppression (e.g., Luteinizing Hormone&#xD;
             Releasing Hormone [LHRH] agonist) if the patient is not surgically castrate&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 determined within 28&#xD;
             days before enrollment&#xD;
&#xD;
          -  Recovery to CTCAE grade ≤ 1 toxicity, to patient's baseline status (except alopecia),&#xD;
             or toxicities deemed irreversible from the effects of prior cancer therapy (CTCAEs&#xD;
             grade &gt; 1 that are not considered a safety risk by the investigator will be allowed)&#xD;
&#xD;
          -  Adequate bone marrow function defined as:&#xD;
&#xD;
               -  absolute neutrophil count (ANC) &gt; 1500 cells/mm³ without growth factor support&#xD;
&#xD;
               -  platelet count &gt; 100,000 cells/mm³ without transfusion or growth factor support&#xD;
&#xD;
               -  hemoglobin &gt; 9g/dL without transfusion or growth factor support&#xD;
&#xD;
          -  Adequate liver function defined as:&#xD;
&#xD;
               -  total bilirubin &lt; upper limit of normal (ULN)&#xD;
&#xD;
               -  alanine aminotransferase (ALT) &lt; 1.5 x ULN&#xD;
&#xD;
               -  aspartate aminotransferase (AST) &lt; 1.5 x ULN&#xD;
&#xD;
          -  Adequate renal function defined as serum creatinine level within normal limits (WNL)&#xD;
&#xD;
          -  At least a 6-month or greater life expectancy&#xD;
&#xD;
          -  Ability to understand and sign a written informed consent, which will be obtained from&#xD;
             study participants before undergoing any study-specific procedures&#xD;
&#xD;
          -  Willing and able to comply with scheduled visits, treatment plan, laboratory tests,&#xD;
             and other trial procedures&#xD;
&#xD;
          -  Suitable venous access for the study-required blood sampling (i.e., including PK&#xD;
             sampling)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior treatment with antineoplastic chemotherapy or radioisotopes for metastatic&#xD;
             disease&#xD;
&#xD;
          -  Prior adjuvant or neo-adjuvant chemotherapy within 12 months of study entry&#xD;
&#xD;
          -  Last dose of sipuleucel-T therapy within 4 weeks of enrollment&#xD;
&#xD;
          -  Any investigational therapies within 4 weeks of study entry&#xD;
&#xD;
          -  Radiotherapy within 4 weeks of study entry&#xD;
&#xD;
          -  Major surgery within 4 weeks of study entry, and not fully recovered to baseline or a&#xD;
             stable clinical status&#xD;
&#xD;
          -  Uncontrolled high blood pressure (systolic blood pressure &gt; 160mmHg, diastolic blood&#xD;
             pressure &gt; 95mmHg)&#xD;
&#xD;
          -  Receiving chronic steroid therapy. Topical and inhaled steroids are permitted&#xD;
&#xD;
          -  Known severe hypersensitivity reactions to docetaxel or other drugs formulated in&#xD;
             polysorbate 80, or to mushroom products&#xD;
&#xD;
          -  Any comorbid condition or unresolved toxicity that would preclude administration of&#xD;
             docetaxel&#xD;
&#xD;
          -  Medical contraindication to any docetaxel pre-medications&#xD;
&#xD;
          -  History of &gt; grade 2 neurotoxicity or any toxicity from any cause that has not&#xD;
             resolved to &lt; grade 1&#xD;
&#xD;
          -  Brain or other CNS metastasis&#xD;
&#xD;
          -  The need for chronic daily immunosuppressive therapy, including concurrent use of&#xD;
             prednisone&#xD;
&#xD;
          -  Evidence of active second malignancy, except non-melanoma skin cancer&#xD;
&#xD;
          -  Infection requiring intravenous antibiotic therapy or other severe infection within 14&#xD;
             days preceding first dose of study drug&#xD;
&#xD;
          -  Inability to swallow oral medication or maintain a fast, as required 2 hours before&#xD;
             and 1 hour after PSK administration&#xD;
&#xD;
          -  Uncontrolled pain at baseline, impending complication from bone metastasis and/or&#xD;
             presence of urinary obstruction&#xD;
&#xD;
          -  Other medical or psychiatric condition that may increase the risk associated with&#xD;
             trial participation or any other condition in the judgment of the investigator that&#xD;
             may interfere with the interpretation of trial results or would make the patient&#xD;
             inappropriate for enrollment in this trial&#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>Celestia Higano, MD</last_name>
    <role>Study Director</role>
    <affiliation>Seattle Cancer Care Alliance - University of Washington</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Cynthia A Wenner, Ph.D</last_name>
    <role>Study Director</role>
    <affiliation>Bastyr University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Leanna J Standish, PhD, ND, LAc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Bastyr University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mary (Nora) L Disis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Washington</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Seattle Cancer Care Alliance</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.bastyr.edu</url>
    <description>General information of Bastyr University</description>
  </link>
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    <citation>Ikuzawa M, Matsunaga K, Nishiyama S, Nakajima S, Kobayashi Y, Andoh T, Kobayashi A, Ohhara M, Ohmura Y, Wada T, et al. Fate and distribution of an antitumor protein-bound polysaccharide PSK (Krestin). Int J Immunopharmacol. 1988;10(4):415-23. doi: 10.1016/0192-0561(88)90128-2.</citation>
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  <verification_date>October 2015</verification_date>
  <study_first_submitted>September 6, 2012</study_first_submitted>
  <study_first_submitted_qc>September 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 14, 2012</study_first_posted>
  <last_update_submitted>October 23, 2015</last_update_submitted>
  <last_update_submitted_qc>October 23, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 27, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Prostate</keyword>
  <keyword>Neoplasm</keyword>
  <keyword>Adenocarcinoma</keyword>
  <keyword>Cancer</keyword>
  <keyword>Metastatic</keyword>
  <keyword>Castrate resistant</keyword>
  <keyword>Docetaxel</keyword>
  <keyword>PSK</keyword>
  <keyword>Krestin</keyword>
  <keyword>Trametes versicolor</keyword>
  <keyword>Safety</keyword>
  <keyword>Maximum tolerated dose</keyword>
  <keyword>Mushroom</keyword>
  <keyword>Natural</keyword>
  <keyword>Immunotherapy</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>polysaccharide-K</mesh_term>
    <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/NCT01685489
org study id: 1U19AT006028-01A1
nct id: NCT01685489
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
This is a phase 1b study that follows a 3+3 dose escalation design and consists of a 21-day
      lead-in period of oral Polysaccharide Krestin (PSK)/placebo (study drug) alone followed by
      the addition to study drug of standard intravenous docetaxel at 75 mg/m2 every 3 weeks for
      three cycles. Study drug will be discontinued on day 15 of the third docetaxel cycle to allow
      for a 7-day washout period before the fourth dose of docetaxel. Pharmacokinetic (PK) analysis
      of docetaxel will be conducted during docetaxel cycle 1 (combination therapy) and cycle 4
      (docetaxel alone). Serum for future PSK PK analysis will be collected on days 1, 3, and 15 of
      PSK/placebo lead-in and during cycles 1 and 4.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Determine tolerability dose of PSK alone and in combination with docetaxel
time frame: 42 days
description: Adverse events are graded to determine a dose limiting toxicity of PSK during the lead-in PSK alone and during the docetaxel treatment in combination with PSK.
measure: Determine maximum tolerated dose and recommended phase 2 dose of PSK in combination with docetaxel
time frame: 106 days
description: When the maximum tolerated dose is determined, a total of 15 patients will be treated with the recommended phase 2 dose with the combination of docetaxel chemotherapy.
measure: Pharmacokinetics of docetaxel when combined with oral PSK
time frame: 106 days
description: The plasma docetaxel levels are analyzed at eight time points during the cycle 1 of standard intravenous docetaxel at 75 mg/m2 with oral PSK/Placebo. After the seven-day washout of PSK/placebo at the cycle 3, the plasma docetaxel levels are analyzed again at eight time points during the cycle 4 of docetaxel treatment without PSK/Placebo.
measure: Pharmacokinetics of oral PSK dosing and in combination with docetaxel
time frame: 106 days
description: The serum PSK levels are analyzed at two time points during the lead-in cycle and eight time points during the cycle 1 of standard intravenous docetaxel at 75 mg/m2 with oral PSK/Placebo. After the seven-day washout of PSK/placebo at the cycle 3, the plasma docetaxel levels are analyzed again at eight time points during the cycle 4 of docetaxel treatment without PSK/Placebo.
measure: Immunological laboratory analysis
time frame: 106 days
description: Natural Killer (NK) cell functional activity, distributions of NK, B, and T cells, and IFN-gamma and TNF-alpha production capacity are analyzed and compared to those of the placebo group.
measure: Clinical tumor markers
time frame: 106 days
description: Circulating tumor cell (CTC) and prostate specific antigen (PSA) levels are compared to that of the placebo group during the oral PSK lead-in period and during the combination therapy with docetaxel and PSK.
measure: Prostatic acid phosphatase
time frame: 106
description: The serum level of prostatic acid phosphatase levels are compared to that of the placebo group during the oral PSK lead-in period and during the combination therapy with docetaxel and PSK.
arm group label: Docetaxel, PSK®
arm group type: Experimental
description: A 21-day lead-in oral PSK alone is followed by the addition of standard intravenous docetaxel at 75 mg/m2 evey 3 weeks for three cycles. After the third dose of docetaxel, study drug will be discontinued on day 14 to allow for a 7-day washout period before a fourth dose of docetaxel is administered.
arm group label: Docetaxel, Placebo
arm group type: Placebo Comparator
description: A 21-day lead-in oral placebo alone is followed by the addition of standard intravenous docetaxel at 75 mg/m2 every 3 weeks for three cycles. After the third dose of docetaxel, the placebo will be discontinued on day 14 to allow for a 7-day washout period before a fourth dose of docetaxel is administered.
intervention type: Drug
intervention name: Docetaxel, PSK®
arm group label: Docetaxel, PSK®
other name: Polysaccharide-K
other name: Krestin
other name: Polysaccharide-Kureha
intervention type: Drug
intervention name: Docetaxel, Placebo
arm group label: Docetaxel, Placebo
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Celestia Higano, MD
role: Study Director
affiliation: Seattle Cancer Care Alliance - University of Washington
last name: Cynthia A Wenner, Ph.D
role: Study Director
affiliation: Bastyr University
last name: Leanna J Standish, PhD, ND, LAc
role: Principal Investigator
affiliation: Bastyr University
last name: Mary (Nora) L Disis, MD
role: Principal Investigator
affiliation: University of Washington
facility: 
country: United States
url: http://www.bastyr.edu
description: General information of Bastyr University
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responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: polysaccharide-K
mesh term: Docetaxel