xml: <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/NCT06039371</url>
    </required_header>
    <id_info>
      <org_study_id>RG1123642</org_study_id>
      <secondary_id>NCI-2023-05597</secondary_id>
      <secondary_id>STUDY00018098</secondary_id>
      <nct_id>NCT06039371</nct_id>
    </id_info>
    <brief_title>Supraphysiological Androgen to Enhance Chemotherapy Treatment Activity in Metastatic Castration-Resistant Prostate Cancer, SPECTRA Study</brief_title>
    <official_title>SPECTRA: SupraPhysiological Androgen to Enhance Chemotherapy TReatment Activity</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Washington</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of Washington</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This phase II trial studies how well giving testosterone at levels higher than normally found&#xD;
        in the body (supraphysiological) works to enhance chemotherapy treatment in patients with&#xD;
        prostate cancer that has progressed despite being previously treated with androgen therapies&#xD;
        and has spread from where it first started (prostate) to other places in the body (metastatic&#xD;
        castration-resistant prostate cancer). In patients that have developed progressive cancer in&#xD;
        spite of standard hormonal treatment, administering supraphysiological testosterone may&#xD;
        result in regression of tumors by causing deoxyribonucleic acid (DNA) damage in tumor cells&#xD;
        that have adapted to low testosterone conditions. Carboplatin is in a class of medications&#xD;
        known as platinum-containing compounds. Carboplatin works by killing, stopping or slowing the&#xD;
        growth of tumor cells. Etoposide is in a class of medications known as podophyllotoxin&#xD;
        derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill&#xD;
        tumor cells. Giving supraphysiological levels of testosterone and carboplatin or etoposide&#xD;
        together may be an effective treatment for metastatic castration-resistant prostate cancer.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        OUTLINE: Patients are randomized to 1 of 2 cohorts.&#xD;
  &#xD;
        COHORT I: Patients are then assigned to 1 of 3 sub-cohorts within cohort I.&#xD;
  &#xD;
        COHORT Ia: Patients continue to receive ADT and receive testosterone cypionate&#xD;
        intramuscularly (IM) on day 1 of cycle 1. Patients then receive testosterone cypionate IM and&#xD;
        carboplatin intravenously (IV) on day 1 of subsequent cycles. Cycles repeat every 28 days in&#xD;
        the absence of disease progression or unacceptable toxicity.&#xD;
  &#xD;
        COHORT Ib: Patients continue to receive ADT and receive carboplatin IV on day 1 of cycle 1.&#xD;
        Patients then receive testosterone cypionate IM and carboplatin IV on day 1 of subsequent&#xD;
        cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable&#xD;
        toxicity.&#xD;
  &#xD;
        COHORT Ic: Patients continue to receive ADT and receive testosterone cypionate IM and&#xD;
        carboplatin IV on day 1 of cycle 1. Patients then receive testosterone cypionate IM and&#xD;
        carboplatin IV on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of&#xD;
        disease progression or unacceptable toxicity.&#xD;
  &#xD;
        COHORT II: Patients are then assigned to 1 of 3 sub-cohorts within cohort II.&#xD;
  &#xD;
        COHORT IIa: Patients continue to receive ADT and receive testosterone cypionate IM on day 1&#xD;
        of cycle 1. Patients then receive testosterone cypionate IM on day 1 and etoposide orally&#xD;
        (PO) once daily (QD) on days 1-14 of subsequent cycles. Cycles repeat every 28 days in the&#xD;
        absence of disease progression or unacceptable toxicity.&#xD;
  &#xD;
        COHORT IIb: Patients continue to receive ADT and receive etoposide PO QD on days 1-14 of&#xD;
        cycle 1. Patients then receive testosterone cypionate IM on day 1 and etoposide PO QD on days&#xD;
        1-14 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression&#xD;
        or unacceptable toxicity.&#xD;
  &#xD;
        COHORT IIc: Patients continue to receive ADT and receive testosterone cypionate IM on day 1&#xD;
        and etoposide PO QD on days 1-14 of cycle 1. Patients then receive testosterone cypionate IM&#xD;
        on day 1 and etoposide PO QD on days 1-14 of subsequent cycles. Cycles repeat every 28 days&#xD;
        in the absence of disease progression or unacceptable toxicity.&#xD;
  &#xD;
        All patients undergo a biopsy on study and blood sample collection on study, and bone scans&#xD;
        and computed tomography (CT) scans throughout the trial. Patients may also undergo an&#xD;
        optional second biopsy at the end of study treatment.&#xD;
  &#xD;
        After completion of study treatment, patients are followed up at 30 days, and then every 6&#xD;
        months for 2 years.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">January 1, 2024</start_date>
    <completion_date type="Anticipated">December 31, 2027</completion_date>
    <primary_completion_date type="Anticipated">March 31, 2027</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>Greater than or equal to 50% decline in prostate-specific antigen from baseline (PSA50) response rate</measure>
      <time_frame>From baseline up to 3 years</time_frame>
      <description>Will assess &gt;= 50% decline in PSA following treatment with combination bipolar androgen therapy (BAT) and genotoxic chemotherapy (at least 16 weeks of total therapy). Will be calculated as the percentage with 95% confidence interval (CI) of the total number of subjects that achieved a PSA50 response.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Radiographic response</measure>
      <time_frame>Up to 3 years</time_frame>
      <description>Will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Best radiographic response for each patient will be presented in a waterfall plot.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Radiographic progression-free survival (PFS)</measure>
      <time_frame>The start of treatment until disease progression (per modified RECIST criteria or PCWG3 criteria for bone lesions), clinical progression (as determined by the treating physician), or death, whichever occurs first, assessed up to 3 years</time_frame>
      <description>Will be assessed using RECIST 1.1 and Prostate Cancer Working Group 3 (PCWG3) criteria. Will be presented with Kaplan-Meier curves, and the median survival with 95% CI will be calculated. Rates will be reported as percentages with 95% CI.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PSA PFS</measure>
      <time_frame>Time from the start of treatment until PSA progression (as defined by PCWG3 criteria), assessed up to 3 years</time_frame>
      <description>Will be assessed using PCWG3 criteria. Will be presented with Kaplan-Meier curves, and the median survival with 95% CI will be calculated. Rates will be reported as percentages with 95% CI. Best on study PSA for each patient will be presented in a waterfall plot.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival</measure>
      <time_frame>The start of treatment until death from any cause, assessed up to 3 years</time_frame>
      <description>Will be presented with Kaplan-Meier curves, and the median survival with 95% CI will be calculated. Rates will be reported as percentages with 95% CI.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Functional Assessment of Cancer Therapy - Prostate (FACT-P)</measure>
      <time_frame>Up to 3 years</time_frame>
      <description>Will be assessed by average change in quality of life (QOL) scores (total and for each domain) for each survey will be calculated at each timepoint. A paired t-test will used to assess for statistically significant changes in QOL from baseline to subsequent timepoints, and linear mixed effects models will be used to evaluate trends over all timepoints.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>International Index of Erectile Function (IIEF)</measure>
      <time_frame>Up to 3 years</time_frame>
      <description>Will be assessed by average change in quality of life (QOL) scores (total and for each domain) for each survey will be calculated at each timepoint. A paired t-test will used to assess for statistically significant changes in QOL from baseline to subsequent timepoints, and linear mixed effects models will be used to evaluate trends over all timepoints.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of adverse events</measure>
      <time_frame>Up to 30 days after completion of study treatment</time_frame>
      <description>Will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.</description>
    </secondary_outcome>
    <number_of_arms>6</number_of_arms>
    <enrollment type="Anticipated">46</enrollment>
    <condition>Castration-Resistant Prostate Carcinoma</condition>
    <condition>Metastatic Prostate Adenocarcinoma</condition>
    <condition>Stage IV Prostate Cancer AJCC v8</condition>
    <arm_group>
      <arm_group_label>Cohort Ia (testosterone cypionate, carboplatin)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Patients continue to receive ADT per standard of care and receive testosterone cypionate IM on day 1 of cycle 1. Patients then receive testosterone cypionate IM and carboplatin IV on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. All patients undergo a biopsy, blood sample collection, bone scan and CT scan throughout the study.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cohort Ib (testosterone cypionate, carboplatin)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Patients continue to receive ADT per standard of care and receive carboplatin IV on day 1 of cycle 1. Patients then receive testosterone cypionate IM and carboplatin IV on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. All patients undergo a biopsy, blood sample collection, bone scan and CT scan throughout the study.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cohort Ic (testosterone cypionate, carboplatin)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients continue to receive ADT per standard of care and receive testosterone cypionate IM and carboplatin IV on day 1 of cycle 1. Patients then receive testosterone cypionate IM and carboplatin IV on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. All patients undergo a biopsy, blood sample collection, bone scan and CT scan throughout the study.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cohort IIa (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Patients continue to receive ADT per standard of care and receive testosterone cypionate IM on day 1 of cycle 1. Patients then receive testosterone cypionate IM on day 1 and etoposide PO QD on days 1-14 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. All patients undergo a biopsy, blood sample collection, bone scan and CT scan throughout the study.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cohort IIb (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Patients continue to receive ADT per standard of care and receive etoposide PO QD on days 1-14 of cycle 1. Patients then receive testosterone cypionate IM on day 1 and etoposide PO QD on days 1-14 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. All patients undergo a biopsy, blood sample collection, bone scan and CT scan throughout the study.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cohort IIc (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients continue to receive ADT per standard of care and receive testosterone cypionate IM on day 1 and etoposide PO QD on days 1-14 of cycle 1. Patients then receive testosterone cypionate IM on day 1 and etoposide PO QD on days 1-14 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. All patients undergo a biopsy, blood sample collection, bone scan and CT scan throughout the study.</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Biopsy</intervention_name>
      <description>Undergo a biopsy</description>
      <arm_group_label>Cohort IIa (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_label>Cohort IIb (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_label>Cohort IIc (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_label>Cohort Ia (testosterone cypionate, carboplatin)</arm_group_label>
      <arm_group_label>Cohort Ib (testosterone cypionate, carboplatin)</arm_group_label>
      <arm_group_label>Cohort Ic (testosterone cypionate, carboplatin)</arm_group_label>
      <other_name>BIOPSY_TYPE</other_name>
      <other_name>Bx</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Biospecimen Collection</intervention_name>
      <description>Undergo blood sample collection</description>
      <arm_group_label>Cohort IIa (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_label>Cohort IIb (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_label>Cohort IIc (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_label>Cohort Ia (testosterone cypionate, carboplatin)</arm_group_label>
      <arm_group_label>Cohort Ib (testosterone cypionate, carboplatin)</arm_group_label>
      <arm_group_label>Cohort Ic (testosterone cypionate, carboplatin)</arm_group_label>
      <other_name>Biological Sample Collection</other_name>
      <other_name>Biospecimen Collected</other_name>
      <other_name>Specimen Collection</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Bone Scan</intervention_name>
      <description>Undergo bone scan</description>
      <arm_group_label>Cohort IIa (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_label>Cohort IIb (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_label>Cohort IIc (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_label>Cohort Ia (testosterone cypionate, carboplatin)</arm_group_label>
      <arm_group_label>Cohort Ib (testosterone cypionate, carboplatin)</arm_group_label>
      <arm_group_label>Cohort Ic (testosterone cypionate, carboplatin)</arm_group_label>
      <other_name>Bone Scintigraphy</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Carboplatin</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Cohort Ia (testosterone cypionate, carboplatin)</arm_group_label>
      <arm_group_label>Cohort Ib (testosterone cypionate, carboplatin)</arm_group_label>
      <arm_group_label>Cohort Ic (testosterone cypionate, carboplatin)</arm_group_label>
      <other_name>Blastocarb</other_name>
      <other_name>Carboplat</other_name>
      <other_name>Carboplatin Hexal</other_name>
      <other_name>Carboplatino</other_name>
      <other_name>Carboplatinum</other_name>
      <other_name>Carbosin</other_name>
      <other_name>Carbosol</other_name>
      <other_name>Carbotec</other_name>
      <other_name>CBDCA</other_name>
      <other_name>Displata</other_name>
      <other_name>Ercar</other_name>
      <other_name>JM-8</other_name>
      <other_name>Nealorin</other_name>
      <other_name>Novoplatinum</other_name>
      <other_name>Paraplatin</other_name>
      <other_name>Paraplatin AQ</other_name>
      <other_name>Paraplatine</other_name>
      <other_name>Platinwas</other_name>
      <other_name>Ribocarbo</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Computed Tomography</intervention_name>
      <description>Undergo CT</description>
      <arm_group_label>Cohort IIa (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_label>Cohort IIb (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_label>Cohort IIc (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_label>Cohort Ia (testosterone cypionate, carboplatin)</arm_group_label>
      <arm_group_label>Cohort Ib (testosterone cypionate, carboplatin)</arm_group_label>
      <arm_group_label>Cohort Ic (testosterone cypionate, carboplatin)</arm_group_label>
      <other_name>CAT</other_name>
      <other_name>CAT Scan</other_name>
      <other_name>Computed Axial Tomography</other_name>
      <other_name>Computerized Axial Tomography</other_name>
      <other_name>Computerized axial tomography (procedure)</other_name>
      <other_name>Computerized Tomography</other_name>
      <other_name>CT</other_name>
      <other_name>CT Scan</other_name>
      <other_name>tomography</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Etoposide</intervention_name>
      <description>Given PO</description>
      <arm_group_label>Cohort IIa (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_label>Cohort IIb (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_label>Cohort IIc (testosterone cypionate, etoposide)</arm_group_label>
      <other_name>Demethyl Epipodophyllotoxin Ethylidine Glucoside</other_name>
      <other_name>EPEG</other_name>
      <other_name>Lastet</other_name>
      <other_name>Toposar</other_name>
      <other_name>Vepesid</other_name>
      <other_name>VP 16</other_name>
      <other_name>VP 16-213</other_name>
      <other_name>VP-16</other_name>
      <other_name>VP-16-213</other_name>
      <other_name>VP16</other_name>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Quality-of-Life Assessment</intervention_name>
      <description>Ancillary studies</description>
      <arm_group_label>Cohort IIa (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_label>Cohort IIb (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_label>Cohort IIc (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_label>Cohort Ia (testosterone cypionate, carboplatin)</arm_group_label>
      <arm_group_label>Cohort Ib (testosterone cypionate, carboplatin)</arm_group_label>
      <arm_group_label>Cohort Ic (testosterone cypionate, carboplatin)</arm_group_label>
      <other_name>Quality of Life Assessment</other_name>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Questionnaire Administration</intervention_name>
      <description>Ancillary studies</description>
      <arm_group_label>Cohort IIa (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_label>Cohort IIb (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_label>Cohort IIc (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_label>Cohort Ia (testosterone cypionate, carboplatin)</arm_group_label>
      <arm_group_label>Cohort Ib (testosterone cypionate, carboplatin)</arm_group_label>
      <arm_group_label>Cohort Ic (testosterone cypionate, carboplatin)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Testosterone Cypionate</intervention_name>
      <description>Given IM</description>
      <arm_group_label>Cohort IIa (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_label>Cohort IIb (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_label>Cohort IIc (testosterone cypionate, etoposide)</arm_group_label>
      <arm_group_label>Cohort Ia (testosterone cypionate, carboplatin)</arm_group_label>
      <arm_group_label>Cohort Ib (testosterone cypionate, carboplatin)</arm_group_label>
      <arm_group_label>Cohort Ic (testosterone cypionate, carboplatin)</arm_group_label>
      <other_name>depAndro</other_name>
      <other_name>Depo-Testosterone</other_name>
      <other_name>Depotest</other_name>
      <other_name>Depovirin</other_name>
      <other_name>Pertestis</other_name>
      <other_name>Virilon</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Must be willing to provide informed consent prior to any study specific procedures&#xD;
  &#xD;
            -  Age &gt;= 18 years&#xD;
  &#xD;
            -  Documented histologically confirmed adenocarcinoma of the prostate&#xD;
  &#xD;
            -  Patient must have evidence of castration resistant prostate cancer as evidenced by PSA&#xD;
               progression (per Prostate Cancer Working Group 3 [PCWG3] criteria) and a castrate&#xD;
               serum testosterone level (i.e., =&lt; 50 mg/dL)&#xD;
  &#xD;
            -  PSA must be at least 2 ng/ml and rising on two successive measurements at least two&#xD;
               weeks apart&#xD;
  &#xD;
            -  Patients must have progressed on abiraterone and/or enzalutamide. There must be at&#xD;
               least a 2-week washout period after stopping the most recent approved therapy for&#xD;
               metastatic castration-resistant prostate cancer (mCRPC) (i.e., abiraterone,&#xD;
               enzalutamide, Ra-223, sipuleucel-t) prior to cycle 1, day 1. If applicable, patients&#xD;
               should be weaned off steroids at least 1 week prior to starting treatment&#xD;
  &#xD;
            -  No prior chemotherapy for the treatment of mCRPC. Patients may have received docetaxel&#xD;
               for the treatment of hormone-sensitive prostate cancer&#xD;
  &#xD;
            -  Prior treatment with non-chemotherapy investigational agents is permitted. There must&#xD;
               be at least a 2-week washout period after stopping any investigational cancer agent&#xD;
               prior to cycle 1, day 1&#xD;
  &#xD;
            -  Hemoglobin &gt;= 9 g/dL with no blood transfusion in the past 28 days (within 30 days&#xD;
               prior to administration of study treatment)&#xD;
  &#xD;
            -  Absolute neutrophil count (ANC) &gt;= 1.5 x 10^9/L (within 30 days prior to&#xD;
               administration of study treatment)&#xD;
  &#xD;
            -  Platelet count &gt;= 100 x 10^9/L (within 30 days prior to administration of study&#xD;
               treatment)&#xD;
  &#xD;
            -  Total bilirubin =&lt; 1.5 x institutional upper limit of normal (ULN) (within 30 days&#xD;
               prior to administration of study treatment)&#xD;
  &#xD;
            -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) /&#xD;
               alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =&lt; 2.5 x&#xD;
               institutional upper limit of normal unless liver metastases are present in which case&#xD;
               they must be =&lt; 5x ULN (within 30 days prior to administration of study treatment)&#xD;
  &#xD;
            -  Patients must have creatinine clearance estimated using the Cockcroft-Gault equation&#xD;
               or based on 24 hour urine test of &gt;= 51 mL/min (within 30 days prior to administration&#xD;
               of study treatment)&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) performance status =&lt; 2&#xD;
  &#xD;
            -  Patients must have a life expectancy &gt;= 16 weeks&#xD;
  &#xD;
            -  Patient is willing and able to comply with the protocol for the duration of the study&#xD;
               including undergoing treatment and scheduled visits and examinations&#xD;
  &#xD;
            -  At least one lesion (measurable and/or non-measurable) that can be accurately assessed&#xD;
               at baseline by CT, positron emission tomography (PET), magnetic resonance imaging&#xD;
               (MRI) and/or bone scan and is suitable for repeated assessment&#xD;
  &#xD;
            -  Must be willing to undergo metastatic biopsy&#xD;
  &#xD;
            -  Male patients and their partners, who are sexually active and of childbearing&#xD;
               potential, must agree to the use of two highly effective forms of contraception in&#xD;
               combination, throughout the period of taking study treatment and for 6 months after&#xD;
               last dose of study drug(s) to prevent pregnancy in a partner&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Involvement in the planning and/or conduct of the study&#xD;
  &#xD;
            -  Other malignancy unless curatively treated with no evidence of disease for &gt;= 2 years&#xD;
               except: adequately treated non-melanoma skin cancer, non-muscle invasive bladder&#xD;
               cancer&#xD;
  &#xD;
            -  Persistent toxicities (Common Terminology Criteria for Adverse Event (CTCAE) grade &gt;&#xD;
               2) caused by previous cancer therapy, excluding alopecia&#xD;
  &#xD;
            -  Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence&#xD;
               of brain metastases is not required. Patients with spinal cord compression unless&#xD;
               considered to have received definitive treatment for this and evidence of clinically&#xD;
               stable disease for 28 days&#xD;
  &#xD;
            -  Use of corticosteroids at a dose equivalent to &gt; 10 mg of prednisone daily&#xD;
  &#xD;
            -  Planning to receive concurrent treatment with another systemic cancer therapy, aside&#xD;
               from a luteinizing hormone releasing hormone (LHRH) analogue&#xD;
  &#xD;
            -  Use of warfarin is not permitted. Low-molecular weight heparin and direct oral&#xD;
               anticoagulants are allowed, but their use should be discussed with the principal&#xD;
               investigator (PI) first&#xD;
  &#xD;
            -  Major surgery within 2 weeks of starting study treatment and patients must have&#xD;
               recovered from any effects of any major surgery&#xD;
  &#xD;
            -  Patients considered a poor medical risk due to a serious, uncontrolled medical&#xD;
               disorder, non-malignant systemic disease or active, uncontrolled infection. Examples&#xD;
               include, but are not limited to, uncontrolled ventricular arrhythmia, history of prior&#xD;
               myocardial infarction, uncontrolled major seizure disorder, uncontrolled hypertension&#xD;
               (blood pressure [BP] &gt;= 165/100), history of prior stroke, unstable spinal cord&#xD;
               compression, superior vena cava syndrome, extensive interstitial bilateral lung&#xD;
               disease or any psychiatric disorder that prohibits obtaining informed consent&#xD;
  &#xD;
            -  Patients with a known hypersensitivity to the testosterone cypionate, etoposide,&#xD;
               carboplatin or any of the excipients of these products&#xD;
  &#xD;
            -  Patients with known active hepatitis (i.e., hepatitis B or C) due to risk of&#xD;
               transmitting the infection through blood or other body fluids&#xD;
  &#xD;
            -  Evidence of serious and/or unstable pre-existing medical, psychiatric or other&#xD;
               condition (including laboratory abnormalities) that could interfere with patient&#xD;
               safety or provision of informed consent to participate in this study&#xD;
  &#xD;
            -  Any psychological, familial, sociological, or geographical condition that could&#xD;
               potentially interfere with compliance with the study protocol and follow-up schedule&#xD;
  &#xD;
            -  Evidence of disease that, in the opinion of the investigator, would put the patient at&#xD;
               risk from testosterone therapy (e.g. femoral metastases with concern over fracture&#xD;
               risk, spinal metastases with concern over spinal cord compression, lymph node disease&#xD;
               with concern for ureteral obstruction)&#xD;
  &#xD;
            -  Patients with pain attributable to their prostate cancer.&#xD;
  &#xD;
                 -  Excluded due to concern for pain flare due to testosterone supplementation&#xD;
  &#xD;
            -  Tumor causing urinary outlet obstruction that requires catheterization for voiding.&#xD;
               Patients that require catheterization to void secondary to benign strictures or other&#xD;
               non-cancer causes will be permitted to enroll. Patients with percutaneous nephrostomy&#xD;
               tubes will also be permitted to enroll&#xD;
  &#xD;
            -  Prior history of deep venous thrombosis or pulmonary embolism within 5 years prior to&#xD;
               enrollment in the study and not currently on systemic anticoagulation.&#xD;
  &#xD;
                 -  Excluded due to risk of venous thromboembolism from hormone supplementation&#xD;
  &#xD;
            -  Patients with NYHA (New York Heart Association) class III or IV heart failure or&#xD;
               history of a prior myocardial infarction (MI) with 5 years of enrollment to the study.&#xD;
  &#xD;
                 -  Excluded due to increased risk of cardiovascular events with testosterone&#xD;
                    supplementation&#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>Michael Schweizer</last_name>
      <role>Principal Investigator</role>
      <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Michael Schweizer</last_name>
      <phone>206-606-6252</phone>
      <email>schweize@uw.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>Fred Hutch/University of Washington Cancer Consortium</name>
        <address>
          <city>Seattle</city>
          <state>Washington</state>
          <zip>98109</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Michael Schweizer</last_name>
        <phone>206-606-6252</phone>
        <email>schweize@uw.edu</email>
      </contact>
      <investigator>
        <last_name>Michael Schweizer</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 21, 2023</study_first_submitted>
    <study_first_submitted_qc>September 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 15, 2023</study_first_posted>
    <last_update_submitted>September 8, 2023</last_update_submitted>
    <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 15, 2023</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>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carboplatin</mesh_term>
      <mesh_term>Etoposide</mesh_term>
      <mesh_term>Etoposide phosphate</mesh_term>
      <mesh_term>Methyltestosterone</mesh_term>
      <mesh_term>Podophyllotoxin</mesh_term>
      <mesh_term>Testosterone</mesh_term>
      <mesh_term>Testosterone undecanoate</mesh_term>
      <mesh_term>Testosterone enanthate</mesh_term>
      <mesh_term>Testosterone 17 beta-cypionate</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06039371
  org study id: RG1123642
  secondary id: NCI-2023-05597
  secondary id: STUDY00018098
  nct id: NCT06039371
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This phase II trial studies how well giving testosterone at levels higher than normally found
        in the body (supraphysiological) works to enhance chemotherapy treatment in patients with
        prostate cancer that has progressed despite being previously treated with androgen therapies
        and has spread from where it first started (prostate) to other places in the body (metastatic
        castration-resistant prostate cancer). In patients that have developed progressive cancer in
        spite of standard hormonal treatment, administering supraphysiological testosterone may
        result in regression of tumors by causing deoxyribonucleic acid (DNA) damage in tumor cells
        that have adapted to low testosterone conditions. Carboplatin is in a class of medications
        known as platinum-containing compounds. Carboplatin works by killing, stopping or slowing the
        growth of tumor cells. Etoposide is in a class of medications known as podophyllotoxin
        derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill
        tumor cells. Giving supraphysiological levels of testosterone and carboplatin or etoposide
        together may be an effective treatment for metastatic castration-resistant prostate cancer.
  OUTLINE: Patients are randomized to 1 of 2 cohorts.
  
        COHORT I: Patients are then assigned to 1 of 3 sub-cohorts within cohort I.
  
        COHORT Ia: Patients continue to receive ADT and receive testosterone cypionate
        intramuscularly (IM) on day 1 of cycle 1. Patients then receive testosterone cypionate IM and
        carboplatin intravenously (IV) on day 1 of subsequent cycles. Cycles repeat every 28 days in
        the absence of disease progression or unacceptable toxicity.
  
        COHORT Ib: Patients continue to receive ADT and receive carboplatin IV on day 1 of cycle 1.
        Patients then receive testosterone cypionate IM and carboplatin IV on day 1 of subsequent
        cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable
        toxicity.
  
        COHORT Ic: Patients continue to receive ADT and receive testosterone cypionate IM and
        carboplatin IV on day 1 of cycle 1. Patients then receive testosterone cypionate IM and
        carboplatin IV on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of
        disease progression or unacceptable toxicity.
  
        COHORT II: Patients are then assigned to 1 of 3 sub-cohorts within cohort II.
  
        COHORT IIa: Patients continue to receive ADT and receive testosterone cypionate IM on day 1
        of cycle 1. Patients then receive testosterone cypionate IM on day 1 and etoposide orally
        (PO) once daily (QD) on days 1-14 of subsequent cycles. Cycles repeat every 28 days in the
        absence of disease progression or unacceptable toxicity.
  
        COHORT IIb: Patients continue to receive ADT and receive etoposide PO QD on days 1-14 of
        cycle 1. Patients then receive testosterone cypionate IM on day 1 and etoposide PO QD on days
        1-14 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression
        or unacceptable toxicity.
  
        COHORT IIc: Patients continue to receive ADT and receive testosterone cypionate IM on day 1
        and etoposide PO QD on days 1-14 of cycle 1. Patients then receive testosterone cypionate IM
        on day 1 and etoposide PO QD on days 1-14 of subsequent cycles. Cycles repeat every 28 days
        in the absence of disease progression or unacceptable toxicity.
  
        All patients undergo a biopsy on study and blood sample collection on study, and bone scans
        and computed tomography (CT) scans throughout the trial. Patients may also undergo an
        optional second biopsy at the end of study treatment.
  
        After completion of study treatment, patients are followed up at 30 days, and then every 6
        months for 2 years.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Greater than or equal to 50% decline in prostate-specific antigen from baseline (PSA50) response rate
  time frame: From baseline up to 3 years
  description: Will assess >= 50% decline in PSA following treatment with combination bipolar androgen therapy (BAT) and genotoxic chemotherapy (at least 16 weeks of total therapy). Will be calculated as the percentage with 95% confidence interval (CI) of the total number of subjects that achieved a PSA50 response.
  measure: Radiographic response
  time frame: Up to 3 years
  description: Will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Best radiographic response for each patient will be presented in a waterfall plot.
  measure: Radiographic progression-free survival (PFS)
  time frame: The start of treatment until disease progression (per modified RECIST criteria or PCWG3 criteria for bone lesions), clinical progression (as determined by the treating physician), or death, whichever occurs first, assessed up to 3 years
  description: Will be assessed using RECIST 1.1 and Prostate Cancer Working Group 3 (PCWG3) criteria. Will be presented with Kaplan-Meier curves, and the median survival with 95% CI will be calculated. Rates will be reported as percentages with 95% CI.
  measure: PSA PFS
  time frame: Time from the start of treatment until PSA progression (as defined by PCWG3 criteria), assessed up to 3 years
  description: Will be assessed using PCWG3 criteria. Will be presented with Kaplan-Meier curves, and the median survival with 95% CI will be calculated. Rates will be reported as percentages with 95% CI. Best on study PSA for each patient will be presented in a waterfall plot.
  measure: Overall survival
  time frame: The start of treatment until death from any cause, assessed up to 3 years
  description: Will be presented with Kaplan-Meier curves, and the median survival with 95% CI will be calculated. Rates will be reported as percentages with 95% CI.
  measure: Functional Assessment of Cancer Therapy - Prostate (FACT-P)
  time frame: Up to 3 years
  description: Will be assessed by average change in quality of life (QOL) scores (total and for each domain) for each survey will be calculated at each timepoint. A paired t-test will used to assess for statistically significant changes in QOL from baseline to subsequent timepoints, and linear mixed effects models will be used to evaluate trends over all timepoints.
  measure: International Index of Erectile Function (IIEF)
  time frame: Up to 3 years
  description: Will be assessed by average change in quality of life (QOL) scores (total and for each domain) for each survey will be calculated at each timepoint. A paired t-test will used to assess for statistically significant changes in QOL from baseline to subsequent timepoints, and linear mixed effects models will be used to evaluate trends over all timepoints.
  measure: Incidence of adverse events
  time frame: Up to 30 days after completion of study treatment
  description: Will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
  arm group label: Cohort Ia (testosterone cypionate, carboplatin)
  arm group type: Active Comparator
  description: Patients continue to receive ADT per standard of care and receive testosterone cypionate IM on day 1 of cycle 1. Patients then receive testosterone cypionate IM and carboplatin IV on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. All patients undergo a biopsy, blood sample collection, bone scan and CT scan throughout the study.
  arm group label: Cohort Ib (testosterone cypionate, carboplatin)
  arm group type: Active Comparator
  description: Patients continue to receive ADT per standard of care and receive carboplatin IV on day 1 of cycle 1. Patients then receive testosterone cypionate IM and carboplatin IV on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. All patients undergo a biopsy, blood sample collection, bone scan and CT scan throughout the study.
  arm group label: Cohort Ic (testosterone cypionate, carboplatin)
  arm group type: Experimental
  description: Patients continue to receive ADT per standard of care and receive testosterone cypionate IM and carboplatin IV on day 1 of cycle 1. Patients then receive testosterone cypionate IM and carboplatin IV on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. All patients undergo a biopsy, blood sample collection, bone scan and CT scan throughout the study.
  arm group label: Cohort IIa (testosterone cypionate, etoposide)
  arm group type: Active Comparator
  description: Patients continue to receive ADT per standard of care and receive testosterone cypionate IM on day 1 of cycle 1. Patients then receive testosterone cypionate IM on day 1 and etoposide PO QD on days 1-14 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. All patients undergo a biopsy, blood sample collection, bone scan and CT scan throughout the study.
  arm group label: Cohort IIb (testosterone cypionate, etoposide)
  arm group type: Active Comparator
  description: Patients continue to receive ADT per standard of care and receive etoposide PO QD on days 1-14 of cycle 1. Patients then receive testosterone cypionate IM on day 1 and etoposide PO QD on days 1-14 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. All patients undergo a biopsy, blood sample collection, bone scan and CT scan throughout the study.
  arm group label: Cohort IIc (testosterone cypionate, etoposide)
  arm group type: Experimental
  description: Patients continue to receive ADT per standard of care and receive testosterone cypionate IM on day 1 and etoposide PO QD on days 1-14 of cycle 1. Patients then receive testosterone cypionate IM on day 1 and etoposide PO QD on days 1-14 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. All patients undergo a biopsy, blood sample collection, bone scan and CT scan throughout the study.
  intervention type: Procedure
  intervention name: Biopsy
  description: Undergo a biopsy
  arm group label: Cohort IIa (testosterone cypionate, etoposide)
  arm group label: Cohort IIb (testosterone cypionate, etoposide)
  arm group label: Cohort IIc (testosterone cypionate, etoposide)
  arm group label: Cohort Ia (testosterone cypionate, carboplatin)
  arm group label: Cohort Ib (testosterone cypionate, carboplatin)
  arm group label: Cohort Ic (testosterone cypionate, carboplatin)
  other name: BIOPSY_TYPE
  other name: Bx
  intervention type: Procedure
  intervention name: Biospecimen Collection
  description: Undergo blood sample collection
  arm group label: Cohort IIa (testosterone cypionate, etoposide)
  arm group label: Cohort IIb (testosterone cypionate, etoposide)
  arm group label: Cohort IIc (testosterone cypionate, etoposide)
  arm group label: Cohort Ia (testosterone cypionate, carboplatin)
  arm group label: Cohort Ib (testosterone cypionate, carboplatin)
  arm group label: Cohort Ic (testosterone cypionate, carboplatin)
  other name: Biological Sample Collection
  other name: Biospecimen Collected
  other name: Specimen Collection
  intervention type: Procedure
  intervention name: Bone Scan
  description: Undergo bone scan
  arm group label: Cohort IIa (testosterone cypionate, etoposide)
  arm group label: Cohort IIb (testosterone cypionate, etoposide)
  arm group label: Cohort IIc (testosterone cypionate, etoposide)
  arm group label: Cohort Ia (testosterone cypionate, carboplatin)
  arm group label: Cohort Ib (testosterone cypionate, carboplatin)
  arm group label: Cohort Ic (testosterone cypionate, carboplatin)
  other name: Bone Scintigraphy
  intervention type: Drug
  intervention name: Carboplatin
  description: Given IV
  arm group label: Cohort Ia (testosterone cypionate, carboplatin)
  arm group label: Cohort Ib (testosterone cypionate, carboplatin)
  arm group label: Cohort Ic (testosterone cypionate, carboplatin)
  other name: Blastocarb
  other name: Carboplat
  other name: Carboplatin Hexal
  other name: Carboplatino
  other name: Carboplatinum
  other name: Carbosin
  other name: Carbosol
  other name: Carbotec
  other name: CBDCA
  other name: Displata
  other name: Ercar
  other name: JM-8
  other name: Nealorin
  other name: Novoplatinum
  other name: Paraplatin
  other name: Paraplatin AQ
  other name: Paraplatine
  other name: Platinwas
  other name: Ribocarbo
  intervention type: Procedure
  intervention name: Computed Tomography
  description: Undergo CT
  arm group label: Cohort IIa (testosterone cypionate, etoposide)
  arm group label: Cohort IIb (testosterone cypionate, etoposide)
  arm group label: Cohort IIc (testosterone cypionate, etoposide)
  arm group label: Cohort Ia (testosterone cypionate, carboplatin)
  arm group label: Cohort Ib (testosterone cypionate, carboplatin)
  arm group label: Cohort Ic (testosterone cypionate, carboplatin)
  other name: CAT
  other name: CAT Scan
  other name: Computed Axial Tomography
  other name: Computerized Axial Tomography
  other name: Computerized axial tomography (procedure)
  other name: Computerized Tomography
  other name: CT
  other name: CT Scan
  other name: tomography
  intervention type: Drug
  intervention name: Etoposide
  description: Given PO
  arm group label: Cohort IIa (testosterone cypionate, etoposide)
  arm group label: Cohort IIb (testosterone cypionate, etoposide)
  arm group label: Cohort IIc (testosterone cypionate, etoposide)
  other name: Demethyl Epipodophyllotoxin Ethylidine Glucoside
  other name: EPEG
  other name: Lastet
  other name: Toposar
  other name: Vepesid
  other name: VP 16
  other name: VP 16-213
  other name: VP-16
  other name: VP-16-213
  other name: VP16
  intervention type: Other
  intervention name: Quality-of-Life Assessment
  description: Ancillary studies
  arm group label: Cohort IIa (testosterone cypionate, etoposide)
  arm group label: Cohort IIb (testosterone cypionate, etoposide)
  arm group label: Cohort IIc (testosterone cypionate, etoposide)
  arm group label: Cohort Ia (testosterone cypionate, carboplatin)
  arm group label: Cohort Ib (testosterone cypionate, carboplatin)
  arm group label: Cohort Ic (testosterone cypionate, carboplatin)
  other name: Quality of Life Assessment
  intervention type: Other
  intervention name: Questionnaire Administration
  description: Ancillary studies
  arm group label: Cohort IIa (testosterone cypionate, etoposide)
  arm group label: Cohort IIb (testosterone cypionate, etoposide)
  arm group label: Cohort IIc (testosterone cypionate, etoposide)
  arm group label: Cohort Ia (testosterone cypionate, carboplatin)
  arm group label: Cohort Ib (testosterone cypionate, carboplatin)
  arm group label: Cohort Ic (testosterone cypionate, carboplatin)
  intervention type: Drug
  intervention name: Testosterone Cypionate
  description: Given IM
  arm group label: Cohort IIa (testosterone cypionate, etoposide)
  arm group label: Cohort IIb (testosterone cypionate, etoposide)
  arm group label: Cohort IIc (testosterone cypionate, etoposide)
  arm group label: Cohort Ia (testosterone cypionate, carboplatin)
  arm group label: Cohort Ib (testosterone cypionate, carboplatin)
  arm group label: Cohort Ic (testosterone cypionate, carboplatin)
  other name: depAndro
  other name: Depo-Testosterone
  other name: Depotest
  other name: Depovirin
  other name: Pertestis
  other name: Virilon
  criteria: 
  gender: Male
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Michael Schweizer
  role: Principal Investigator
  affiliation: Fred Hutch/University of Washington Cancer Consortium
  last name: Michael Schweizer
  phone: 206-606-6252
  email: schweize@uw.edu
  facility: 
  contact: 
  investigator: 
  country: United States
  responsible party type: Sponsor
  mesh term: Prostatic Neoplasms
  mesh term: Carboplatin
  mesh term: Etoposide
  mesh term: Etoposide phosphate
  mesh term: Methyltestosterone
  mesh term: Podophyllotoxin
  mesh term: Testosterone
  mesh term: Testosterone undecanoate
  mesh term: Testosterone enanthate
  mesh term: Testosterone 17 beta-cypionate
  sharing ipd: No