<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/NCT03764540</url>
  </required_header>
  <id_info>
    <org_study_id>MP-02-2018-7545</org_study_id>
    <nct_id>NCT03764540</nct_id>
  </id_info>
  <brief_title>Docetaxel Versus Cabazitaxel Post Abiraterone or Enzalutamide</brief_title>
  <acronym>CABPOSTAAT</acronym>
  <official_title>Randomized Phase II Study of Docetaxel Versus Cabazitaxel Post Abiraterone or Enzalutamide Progression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre hospitalier de l'Université de Montréal (CHUM)</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Genzyme, a Sanofi Company</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre hospitalier de l'Université de Montréal (CHUM)</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Prostate cancer (PCa) is the most frequently diagnosed cancer in Canadian men. While the&#xD;
      majority of PCa is slow growing and responds well to first line treatment, a proportion of&#xD;
      cases (10%) progress to metastatic form resulting in more than 4 000 deaths annually in&#xD;
      Canada and 250 000 worldwide. Currently, first line treatment for PCa includes surgery,&#xD;
      radiation and androgen deprivation therapy (ADT). A rapid evolution in the understanding of&#xD;
      disease biology, combined with approvals of new therapies including immunotherapy, novel&#xD;
      chemotherapy, hormonal agents and a bone calcium matrix-targeted radionuclide, along with&#xD;
      further drugs in development, have made treatment decisions for metastatic&#xD;
      castration-resistant prostate cancer (mCRPC) increasingly complex and challenging.&#xD;
&#xD;
      This is a Phase II Study of Cabazitaxel plus prednisone in patients with metastatic&#xD;
      castration-resistant prostate cancer (mCRPC). The current study is designed to determine if&#xD;
      cabazitaxel will improve progression free survival (PFS) or overall survival (OS).&#xD;
&#xD;
      This study will enroll patients with mCRPC, who have been previously treated and progressed&#xD;
      under docetaxel or abiraterone regimen.&#xD;
&#xD;
      Patients must meet the study eligibility criteria and must be competent to give informed&#xD;
      consent.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, multicenter, national, randomized, open label study, comparing the&#xD;
      efficacy of cabazitaxel at 25 mg/m² plus prednisone (Arm A) over docetaxel at 75mg/m2 plus&#xD;
      prednisone (Arm B) after enzalutamide at 160 mg once daily or abiraterone acetate at 1000 mg&#xD;
      once daily plus prednisone in chemotherapy-naïve patients with mCRPC who have progressed on&#xD;
      abiraterone acetate or enzalutamide.&#xD;
&#xD;
      Each patient will be treated until disease progression, unacceptable toxicity, or patient's&#xD;
      refusal of further study treatment.&#xD;
&#xD;
      All eligible patients will be randomly assigned to either arm A or B in a 1:1 proportion.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 1, 2019</start_date>
  <completion_date type="Anticipated">September 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">July 30, 2024</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>PSA response rate at 6 and 12 months</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>Change from baseline PSA level of at least 50%, PSA partial response is defined as a ≥ 50% decline in PSA from cycle 1 day 1 (baseline) PSA value. This PSA change must be confirmed as sustained by a second PSA value obtained ≥ 3 weeks later.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Radiological progression-free survival (rPFS)</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>Time interval between the date of randomization and the date of the first documentation of any of the following event. Radiological tumor progression by RECIST 1.1 and PCWG2,</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>Time interval from the date of randomization to the date of death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to PSA progression (TTPP)</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>Time interval between the date of randomization and the date of first documented PSA progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor response</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>Measurable by RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of tumor response</measure>
    <time_frame>hrough study completion, an average of 1 year</time_frame>
    <description>Time between the first evaluation at which the tumor response criteria are met and the first documentation of tumor progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain response: BPI-SF pain intensity item scores</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>Decrease by &lt;30% from baseline in the average of BPI-SF pain intensity item scores (items 3, 4, 5, and 6) observed at 2 consecutive evaluations ≥3 weeks apart without increase in analgesic usage score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Pain progression</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>Time interval between the date of randomization and the date of the first documented pain progression</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">214</enrollment>
  <condition>Metastatic Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Cabazitaxel plus prednisone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cabazitaxel: Single-dose vial, containing a total of 60 mg of cabazitaxel expressed as anhydrous and solvent-free basis, per 1.5 mL of solution. Cabazitaxel will be administered by IV route Prednisone will be administered orally, 5 mg twice daily (10 mg per day total dose).&#xD;
Prednisone will be administered by oral route</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Docetaxel plus prednisone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Docetaxel is formulated in polysorbate 80 and commercially available as 80 mg/2.0 mL single-dose vials with accompanying diluent (13% ethanol in water for injection) for IV use.&#xD;
Prednisone will be administered orally, 5 mg twice daily (10 mg per day total dose).&#xD;
Prednisone will be administered by oral route</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cabazitaxel plus prednisone</intervention_name>
    <description>Cabazitaxel 25 mg/m² intravenously on day 1 of each cycle, plus prednisone 10 mg orally given daily.&#xD;
A cycle is defined as a 3-weeks period for a maximum of 10 cycles.</description>
    <arm_group_label>Cabazitaxel plus prednisone</arm_group_label>
    <other_name>Experimental</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Docetaxel plus prednisone</intervention_name>
    <description>Docetaxel 75 mg/m² intravenously on day 1 of each cycle, plus prednisone 10 mg orally given daily.&#xD;
A cycle is defined as a 3-weeks period for a maximum of 10 cycles.</description>
    <arm_group_label>Docetaxel plus prednisone</arm_group_label>
    <other_name>Active Comparator</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of histologically or cytologically confirmed prostate adenocarcinoma.&#xD;
&#xD;
          -  Metastatic disease.&#xD;
&#xD;
          -  Progressive disease (PD) while receiving AR targeted therapy with abiraterone acetate&#xD;
             or enzalutamide by at least one of the following:&#xD;
&#xD;
          -  Progression in measurable disease (RECIST 1.1 criteria). Patient with measurable&#xD;
             disease must have at least one lesion that can be accurately measured in at least one&#xD;
             dimension (longest diameter to be recorded). Each lesion must be at least 10 mm when&#xD;
             measured by computed tomography (CT) [CT scan thickness no greater than 5 mm] or&#xD;
             magnetic resonance imaging (MRI). Lymph nodes should be ≥ 15 mm in short axis. As&#xD;
             defined by PCWG2, if lymph node metastasis is the only evidence of metastasis, it must&#xD;
             be ≥ 20 mm in diameter when measured by spiral CT or MRI. Previously irradiated&#xD;
             lesions, primary prostate lesion and bone lesions will be considered non-measurable&#xD;
             disease, and/or&#xD;
&#xD;
          -  Appearance of 2 or more new bone lesions. They must be confirmed by other imaging&#xD;
             modalities (CT; MRI) if ambiguous results (PCWG2), and/or&#xD;
&#xD;
          -  Rising PSA defined (PCWG2) as at least two consecutive rises in PSA to be documented&#xD;
             over a reference value (measure 1) taken at least one week apart. The first rising PSA&#xD;
             (measure 2) should be taken at least 7 days after the reference value. A third&#xD;
             confirmatory PSA measure is required (2nd beyond the reference level) to be greater&#xD;
             than the second measure and it must be obtained at least 7 days after the 2nd measure.&#xD;
             If this is not the case, a fourth PSA measure is required to be taken and be greater&#xD;
             than the 2nd measure. The third (or the fourth) confirmatory PSA should be taken&#xD;
             within 4 weeks prior to randomization.&#xD;
&#xD;
          -  A PSA value of at least 2 ng/mL is required at study entry.&#xD;
&#xD;
          -  Effective castration (serum testosterone levels ≤0.5 ng/mL).&#xD;
&#xD;
          -  Prior AR targeted therapy (abiraterone acetate or enzalutamide) must be stopped at&#xD;
             least 2 weeks before study treatment.&#xD;
&#xD;
          -  Signed written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Related to methodology:&#xD;
&#xD;
          -  Prior chemotherapy for prostate cancer, except estramustine and except&#xD;
             adjuvant/neoadjuvant treatment completed &gt;3 years ago. Prior treatment with sipuleucel&#xD;
             T immunotherapy is allowed at the condition patient did not received prior&#xD;
             chemotherapy. No further anti-cancer therapy after the previous AR targeted therapy&#xD;
             and before inclusion.&#xD;
&#xD;
          -  Less than 28 days elapsed from prior treatment with radiotherapy or surgery to the&#xD;
             time of randomization.&#xD;
&#xD;
          -  Prior isotope therapy, whole bony pelvic radiotherapy, or radiotherapy to &gt;30% of bone&#xD;
             marrow.&#xD;
&#xD;
          -  Adverse events (excluding alopecia and those listed in the specific exclusion&#xD;
             criteria) from any prior anticancer therapy of grade &gt;1(National Cancer Institute&#xD;
             Common Terminology Criteria [NCI CTCAE] v4.0) at the time of randomization.&#xD;
&#xD;
          -  Less than 18 years (or country's legal age of majority if the legal age is &gt;18 years).&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status &gt;1.&#xD;
&#xD;
          -  History of brain metastases, uncontrolled spinal cord compression, or carcinomatous&#xD;
             meningitis or new evidence of brain or leptomeningeal disease.&#xD;
&#xD;
          -  Prior malignancy. Adequately treated basal cell or squamous cell skin or superficial&#xD;
             (pTis, pTa, and pT1) bladder cancer are allowed, as well as any other cancer for which&#xD;
             treatment has been completed ≥5 years ago and from which the patient has been&#xD;
             disease-free for ≥5 years.&#xD;
&#xD;
          -  Participation in another clinical trial and any concurrent treatment with any&#xD;
             investigational drug within 30 days prior to randomization.&#xD;
&#xD;
          -  Any of the following within 3 months prior to randomization: treatment resistant&#xD;
             peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory&#xD;
             bowel disease, diverticulitis, pulmonary embolism, or other uncontrolled&#xD;
             thromboembolic event.&#xD;
&#xD;
          -  Acquired immunodeficiency syndrome (AIDS-related illnesses) or known HIV disease&#xD;
             requiring antiretroviral treatment.&#xD;
&#xD;
          -  Any severe acute or chronic medical condition which could impair the ability of the&#xD;
             patient to participate to the study or interfere with interpretation of study results,&#xD;
             or patient unable to comply with the study procedures.&#xD;
&#xD;
          -  Patients with reproductive potential who do not agree to use accepted and effective&#xD;
             method of contraception during the study treatment period and up to 6 months after the&#xD;
             last administered dose. The definition of &quot;effective method of contraception&quot; will be&#xD;
             based on the investigator's judgment.&#xD;
&#xD;
        Related to study treatment&#xD;
&#xD;
          -  Known allergies, hypersensitivity or intolerance to prednisone. History of&#xD;
             hypersensitivity to docetaxel or polysorbate 80.&#xD;
&#xD;
          -  Known history of mineralocorticoid excess or deficiency.&#xD;
&#xD;
          -  Unable to swallow a whole tablet or capsule&#xD;
&#xD;
          -  Inadequate organ and bone marrow function as evidenced by:&#xD;
&#xD;
               1. Hemoglobin &lt;10.0 g/dL&#xD;
&#xD;
               2. Absolute neutrophil count &lt;1.5 x 109/L&#xD;
&#xD;
               3. Platelet count &lt;100 x 109/L&#xD;
&#xD;
               4. AST/SGOT and/or ALT/SGPT &gt;1.5 x ULN;&#xD;
&#xD;
               5. Total bilirubin &gt;1.0 x ULN&#xD;
&#xD;
               6. Potassium &lt;3.5 mmol/L&#xD;
&#xD;
               7. Serum albumin &lt;3.0 g/dL&#xD;
&#xD;
               8. Child-Pugh Class B and C&#xD;
&#xD;
               9. Serum Creatinine ≤ 1.5 x ULN,&#xD;
&#xD;
          -  Contraindications to the use of corticosteroid treatment.&#xD;
&#xD;
          -  Symptomatic peripheral neuropathy grade &gt;2 (National Cancer Institute Common&#xD;
             Terminology Criteria for Adverse Events [NCI CTCAE] v.4.0).&#xD;
&#xD;
          -  Clinically significant heart disease as evidenced by myocardial infarction, or&#xD;
             arterial thrombotic events in the past 12 months, severe or unstable angina, or New&#xD;
             York Heart Association (NYHA) Class III or IV heart disease or cardiac left&#xD;
             ventricular ejection fraction (LVEF) measurement of &lt;50% at baseline.&#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>fred Saad, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHUM</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Amal Nadiri, PhD</last_name>
    <phone>514 890-8000</phone>
    <phone_ext>26074</phone_ext>
    <email>amal.nadiri.chum@ssss.gouv.qc.ca</email>
  </overall_contact>
  <location>
    <facility>
      <name>Centre Hospitalier de l'Université de Montréal</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H2X 3E4</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>fred Saad, MD</last_name>
      <phone>5148908000</phone>
      <email>fredsaad@videotron.ca</email>
    </contact>
    <contact_backup>
      <last_name>Amal Nadiri, Ph,D</last_name>
      <phone>514890800026074</phone>
      <email>amal.nadiri.chum@ssss.gouv.qc.ca</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>December 3, 2018</study_first_submitted>
  <study_first_submitted_qc>December 4, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 5, 2018</study_first_posted>
  <last_update_submitted>December 20, 2022</last_update_submitted>
  <last_update_submitted_qc>December 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 21, 2022</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>Prednisone</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/NCT03764540
org study id: MP-02-2018-7545
nct id: NCT03764540
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
Prostate cancer (PCa) is the most frequently diagnosed cancer in Canadian men. While the
      majority of PCa is slow growing and responds well to first line treatment, a proportion of
      cases (10%) progress to metastatic form resulting in more than 4 000 deaths annually in
      Canada and 250 000 worldwide. Currently, first line treatment for PCa includes surgery,
      radiation and androgen deprivation therapy (ADT). A rapid evolution in the understanding of
      disease biology, combined with approvals of new therapies including immunotherapy, novel
      chemotherapy, hormonal agents and a bone calcium matrix-targeted radionuclide, along with
      further drugs in development, have made treatment decisions for metastatic
      castration-resistant prostate cancer (mCRPC) increasingly complex and challenging.

      This is a Phase II Study of Cabazitaxel plus prednisone in patients with metastatic
      castration-resistant prostate cancer (mCRPC). The current study is designed to determine if
      cabazitaxel will improve progression free survival (PFS) or overall survival (OS).

      This study will enroll patients with mCRPC, who have been previously treated and progressed
      under docetaxel or abiraterone regimen.

      Patients must meet the study eligibility criteria and must be competent to give informed
      consent.
This is a prospective, multicenter, national, randomized, open label study, comparing the
      efficacy of cabazitaxel at 25 mg/m² plus prednisone (Arm A) over docetaxel at 75mg/m2 plus
      prednisone (Arm B) after enzalutamide at 160 mg once daily or abiraterone acetate at 1000 mg
      once daily plus prednisone in chemotherapy-naïve patients with mCRPC who have progressed on
      abiraterone acetate or enzalutamide.

      Each patient will be treated until disease progression, unacceptable toxicity, or patient's
      refusal of further study treatment.

      All eligible patients will be randomly assigned to either arm A or B in a 1:1 proportion.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: PSA response rate at 6 and 12 months
time frame: through study completion, an average of 1 year
description: Change from baseline PSA level of at least 50%, PSA partial response is defined as a ≥ 50% decline in PSA from cycle 1 day 1 (baseline) PSA value. This PSA change must be confirmed as sustained by a second PSA value obtained ≥ 3 weeks later.
measure: Radiological progression-free survival (rPFS)
time frame: through study completion, an average of 1 year
description: Time interval between the date of randomization and the date of the first documentation of any of the following event. Radiological tumor progression by RECIST 1.1 and PCWG2,
measure: Overall Survival
time frame: through study completion, an average of 1 year
description: Time interval from the date of randomization to the date of death due to any cause
measure: Time to PSA progression (TTPP)
time frame: through study completion, an average of 1 year
description: Time interval between the date of randomization and the date of first documented PSA progression.
measure: Tumor response
time frame: through study completion, an average of 1 year
description: Measurable by RECIST 1.1
measure: Duration of tumor response
time frame: hrough study completion, an average of 1 year
description: Time between the first evaluation at which the tumor response criteria are met and the first documentation of tumor progression.
measure: Pain response: BPI-SF pain intensity item scores
time frame: through study completion, an average of 1 year
description: Decrease by <30% from baseline in the average of BPI-SF pain intensity item scores (items 3, 4, 5, and 6) observed at 2 consecutive evaluations ≥3 weeks apart without increase in analgesic usage score.
measure: Time to Pain progression
time frame: through study completion, an average of 1 year
description: Time interval between the date of randomization and the date of the first documented pain progression
arm group label: Cabazitaxel plus prednisone
arm group type: Experimental
description: Cabazitaxel: Single-dose vial, containing a total of 60 mg of cabazitaxel expressed as anhydrous and solvent-free basis, per 1.5 mL of solution. Cabazitaxel will be administered by IV route Prednisone will be administered orally, 5 mg twice daily (10 mg per day total dose).
Prednisone will be administered by oral route
arm group label: Docetaxel plus prednisone
arm group type: Active Comparator
description: Docetaxel is formulated in polysorbate 80 and commercially available as 80 mg/2.0 mL single-dose vials with accompanying diluent (13% ethanol in water for injection) for IV use.
Prednisone will be administered orally, 5 mg twice daily (10 mg per day total dose).
Prednisone will be administered by oral route
intervention type: Drug
intervention name: Cabazitaxel plus prednisone
description: Cabazitaxel 25 mg/m² intravenously on day 1 of each cycle, plus prednisone 10 mg orally given daily.
A cycle is defined as a 3-weeks period for a maximum of 10 cycles.
arm group label: Cabazitaxel plus prednisone
other name: Experimental
intervention type: Drug
intervention name: Docetaxel plus prednisone
description: Docetaxel 75 mg/m² intravenously on day 1 of each cycle, plus prednisone 10 mg orally given daily.
A cycle is defined as a 3-weeks period for a maximum of 10 cycles.
arm group label: Docetaxel plus prednisone
other name: Active Comparator
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: fred Saad, MD
role: Principal Investigator
affiliation: CHUM
last name: Amal Nadiri, PhD
phone: 514 890-8000
phone ext: 26074
email: amal.nadiri.chum@ssss.gouv.qc.ca
facility: 
status: Recruiting
contact: 
contact backup: 
country: Canada
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Prednisone
mesh term: Docetaxel