<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/NCT03258320</url>
  </required_header>
  <id_info>
    <org_study_id>PCA-81472709</org_study_id>
    <nct_id>NCT03258320</nct_id>
  </id_info>
  <brief_title>A Randomised Trial of Cabazitaxel, Docetaxel, Mitoxantrone or Satraplatin (CDMS) Plus Surgery for Prostate Cancer Patients Without Metastasis</brief_title>
  <official_title>A Phase I Study of Neoadjuvant Chemotherapy Involving Cabazitaxel, Docetaxel, Mitoxantrone or Satraplatin (CDMS) Followed by Surgery for Patients With High Risk Localized Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Jiao Tong University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fudan University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Qilu Hospital of Shandong University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Shanghai Jiao Tong University School of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Current agents administered in therapeutic regimens of prostate cancer employ different&#xD;
      mechanisms to eliminate neoplastic cells by inducing substantial apoptosis and causing tumor&#xD;
      regression. Treatment with neoadjuvant chemotherapy before radical prostatectomy may better&#xD;
      control the tumor before it has the chance to convert into the disease of&#xD;
      castration-resistant prostate cancer (CRPC), which is finally refractory to most modalities&#xD;
      of clinical intervention with a clinically lethal nature.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Prostate cancer is the development of neoplasia in the prostate, a major gland in the male&#xD;
      reproductive system. While most prostate cancers grow slowly, some can develop relatively&#xD;
      quickly and aggressively. In a later stage of the disease, cancer cells may disseminate from&#xD;
      the prostate to other organs of the body, particularly the bone, lung, brain and lymph node.&#xD;
      Prostate cancer initially cause no symptoms, but in an advanced stage it can cause difficulty&#xD;
      in urinating, blood in the urine, or pain in the pelvis. A non-malignant or precursor form of&#xD;
      prostate cancer known as benign prostatic hyperplasia may produce similar symptoms, although&#xD;
      it is essentially not invasive.&#xD;
&#xD;
      Many prostate cancer patients can be safely followed with active surveillance or watchful&#xD;
      actions. However, the major forms of clinical treatments include a combination of surgery,&#xD;
      radiation, hormone therapy or chemotherapy. If it only occurs inside the prostate, the&#xD;
      disease is generally curable. However, when cancer cells have spread to the bones, cytotoxic&#xD;
      or harsh therapies are necessary. Outcomes depend on a person's age and other health&#xD;
      conditions as well as how aggressive and extensive the cancer is. Most people with prostate&#xD;
      cancer do not end up dying from the disease, and the 5-year survival rate in the United&#xD;
      States is approximately 99%. To date, it is the 2nd most common type of malignancy and the&#xD;
      5th leading cause of cancer-related death in men. In 2012 it affected 1.1 million men and&#xD;
      claimed 307,000 deaths. Prostate cancer occur more frequently in the western countries or&#xD;
      developed world, but incidence rates have been continuously arising in the developing&#xD;
      countries. Clinical detection increased significantly in the 1980s and 1990s in the global&#xD;
      range due to development of the gold standard--PSA testing. Studies of males who died from&#xD;
      unrelated causes have found prostate cancer in 30% to 70% of those over the age of 60.&#xD;
&#xD;
      Most hormone-naive prostate cancers become resistant to treatments after 1-3 years and resume&#xD;
      growth despite hormone therapy, a condition termed as &quot;hormone-refractory prostate cancer&quot;&#xD;
      (HRPC) or &quot;castration-resistant prostate cancer (CRPC)&quot;. The most prevalent chemotherapeutic&#xD;
      agent docetaxel (Taxotere) has been used as a standardized modality for CRPC and provides a&#xD;
      median survival benefit of 2-3 months. A second-line chemotherapy involves cabazitaxel.&#xD;
      Although combination of bevacizumab, docetaxel, thalidomide and prednisone appears effective&#xD;
      in the treatment of CRPC, these agents are usually used after the occurrence of CRPC, not&#xD;
      before. Thus, whether or not these patients should receive chemotherapy prior to development&#xD;
      of CRPC, and whether this approach can prevent the aggressive progression of the disease to a&#xD;
      treatment refractory status, remain largely open but intriguing questions.&#xD;
&#xD;
      In this study, investigators performed a Phase I, single agent exploration, multicenter&#xD;
      clinical trial to establish the treatment efficacy of several chemotherapeutic agents in&#xD;
      patients with high risk localized prostate cancer who have developed the primary cancer in&#xD;
      prostate. Up to 5 cohorts have been enrolled to determine the effectiveness and safety of&#xD;
      single therapeutic strategy. Besides the five-year disease-free survival, overall survival&#xD;
      and five-year metastasis-free survival post treatment, investigators also take into account&#xD;
      the anticancer agent-induced tumor stroma damage extent, which may provide further evidence&#xD;
      to support the treatment efficacy and assess the potential influence of a damaged tumor&#xD;
      microenvironment on disease progression or regression in clinical settings.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 2015</start_date>
  <completion_date type="Anticipated">December 2025</completion_date>
  <primary_completion_date type="Anticipated">December 2024</primary_completion_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>
    <intervention_model_description>Chemotherapy (single agent of CDMS) will be performed 45 days before surgery for patients who are diagnosed with prostate cancer without distant metastasis. The chemotherapy using CDMS will done for 4 cycles within 30 days after first diagnosis of prostate cancer.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
    <masking_description>Both the participants and care providers will be blind to the agents, but the investigators will be aware of and keep track of the whole regime and agents.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>5 years disease-free survival</measure>
    <time_frame>5 years</time_frame>
    <description>There is no disease-associated progression during the 5 years post treatment (chemotherapy plus surgery).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>5 years overall survival and metastasis-free survival</measure>
    <time_frame>5 years</time_frame>
    <description>The overall survival status and distant metastasis-free survival status during the 5 years post treatment (chemotherapy plus surgery).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Prostate Cancer Patients</condition>
  <arm_group>
    <arm_group_label>CDMS, Surgery</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Preoperative chemotherapy using Cabazitaxel, Docetaxel, Mitoxantrone or Satraplatin (CDMS) as a single agent performed 45 days before surgery：Cabazitaxel 25 mg/m2, Docetaxel 35 mg/m2, Mitoxantrone 4 mg/m2 or Satraplatin 80 mg/m2, through intravenous (IV) or oral (Satraplatin) administration. IV or oral administration once every 7 days, totally 4 cycles. There is a 17-day interval between the last dose and surgery.&#xD;
Procedure: radical prostatectomy surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No neoadjuvant chemotherapy using CDMS will be done for patients who are diagnosed with localized prostate cancer but subject to direct surgery to radically remove the primary tumor.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cabazitaxel, Docetaxel, Mitoxantrone or Satraplatin</intervention_name>
    <description>As preoperative neoadjuvant chemotherapy, drugss including Cabazitaxel, Docetaxel, Mitoxantrone or Satraplatin (CDMS) will be administered as a single agent performed 45 days before surgery：Cabazitaxel 25 mg/m2, Docetaxel 35 mg/m2, Mitoxantrone 4 mg/m2 or Satraplatin 80 mg/m2, through intravenous (IV) or oral (Satraplatin) administration. IV or oral administration once every 7 days, totally 4 cycles. There is a 17-day interval between the last dose and surgery.</description>
    <arm_group_label>CDMS, Surgery</arm_group_label>
    <other_name>Jevtana, Taxotere, Novantrone, JM216.</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  40 ≤ age ≤ 75 years with histologically proven PCa&#xD;
&#xD;
          -  no severe major organ dysfunction&#xD;
&#xD;
          -  WHO performance status of 0 or 1&#xD;
&#xD;
          -  no prior cancer chemotherapy&#xD;
&#xD;
          -  A Clinical Stage ≥ T2c (T2c, N0, M0) of prostate cancer but without diagnosed distant&#xD;
             metastasis (according to the 2016 American Joint Committee on Cancer (AJCC) definition&#xD;
             of TNM staging system, Staging Manual, Eighth Edition) as determined by a preoperative&#xD;
             evaluation that included a pleural computed tomography (CT) scan.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  age ≥ 76&#xD;
&#xD;
          -  severe major organ dysfunction&#xD;
&#xD;
          -  WHO performance status of &gt;1&#xD;
&#xD;
          -  prior cancer chemotherapy&#xD;
&#xD;
          -  Stage IV.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>All participant patients should be male, adult.</gender_description>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yu Sun, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shanghai Jiao Tong University School of Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yu Sun, Ph.D</last_name>
    <phone>86-21-54923302</phone>
    <email>sunyu@sibs.ac.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Weijun Ma, Ph.D</last_name>
    <phone>86-21-54923268</phone>
    <email>wjma@sibs.ac.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Qilu Hospital of Shandong University</name>
      <address>
        <city>Qingdao</city>
        <state>Shandong</state>
        <zip>266035</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jiannan Chen, Ph.D</last_name>
      <phone>86-0532-96599654</phone>
      <email>submarinesuny@yahoo.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Zhongshan Hospital</name>
      <address>
        <city>Shanghai</city>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Qilai Long, Ph.D</last_name>
      <phone>86-15821758764</phone>
      <email>long.qilai@zs-hospital.sh.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>August 20, 2017</study_first_submitted>
  <study_first_submitted_qc>August 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 23, 2017</study_first_posted>
  <last_update_submitted>May 3, 2022</last_update_submitted>
  <last_update_submitted_qc>May 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 5, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shanghai Jiao Tong University School of Medicine</investigator_affiliation>
    <investigator_full_name>Yu Sun</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Cabazitaxel</keyword>
  <keyword>Docetaxel</keyword>
  <keyword>Mitoxantrone</keyword>
  <keyword>Satraplatin</keyword>
  <keyword>Surgery</keyword>
  <keyword>Prostate Cancer</keyword>
  <keyword>Localized</keyword>
  <keyword>High Risk</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>Docetaxel</mesh_term>
    <mesh_term>Mitoxantrone</mesh_term>
    <mesh_term>Satraplatin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Investigators are happy to make individual participant data (IPD) available to other researchers upon request, as long as the data are not confidential and not restrained by the ethics policy.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03258320
org study id: PCA-81472709
nct id: NCT03258320
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Current agents administered in therapeutic regimens of prostate cancer employ different
      mechanisms to eliminate neoplastic cells by inducing substantial apoptosis and causing tumor
      regression. Treatment with neoadjuvant chemotherapy before radical prostatectomy may better
      control the tumor before it has the chance to convert into the disease of
      castration-resistant prostate cancer (CRPC), which is finally refractory to most modalities
      of clinical intervention with a clinically lethal nature.
Prostate cancer is the development of neoplasia in the prostate, a major gland in the male
      reproductive system. While most prostate cancers grow slowly, some can develop relatively
      quickly and aggressively. In a later stage of the disease, cancer cells may disseminate from
      the prostate to other organs of the body, particularly the bone, lung, brain and lymph node.
      Prostate cancer initially cause no symptoms, but in an advanced stage it can cause difficulty
      in urinating, blood in the urine, or pain in the pelvis. A non-malignant or precursor form of
      prostate cancer known as benign prostatic hyperplasia may produce similar symptoms, although
      it is essentially not invasive.

      Many prostate cancer patients can be safely followed with active surveillance or watchful
      actions. However, the major forms of clinical treatments include a combination of surgery,
      radiation, hormone therapy or chemotherapy. If it only occurs inside the prostate, the
      disease is generally curable. However, when cancer cells have spread to the bones, cytotoxic
      or harsh therapies are necessary. Outcomes depend on a person's age and other health
      conditions as well as how aggressive and extensive the cancer is. Most people with prostate
      cancer do not end up dying from the disease, and the 5-year survival rate in the United
      States is approximately 99%. To date, it is the 2nd most common type of malignancy and the
      5th leading cause of cancer-related death in men. In 2012 it affected 1.1 million men and
      claimed 307,000 deaths. Prostate cancer occur more frequently in the western countries or
      developed world, but incidence rates have been continuously arising in the developing
      countries. Clinical detection increased significantly in the 1980s and 1990s in the global
      range due to development of the gold standard--PSA testing. Studies of males who died from
      unrelated causes have found prostate cancer in 30% to 70% of those over the age of 60.

      Most hormone-naive prostate cancers become resistant to treatments after 1-3 years and resume
      growth despite hormone therapy, a condition termed as "hormone-refractory prostate cancer"
      (HRPC) or "castration-resistant prostate cancer (CRPC)". The most prevalent chemotherapeutic
      agent docetaxel (Taxotere) has been used as a standardized modality for CRPC and provides a
      median survival benefit of 2-3 months. A second-line chemotherapy involves cabazitaxel.
      Although combination of bevacizumab, docetaxel, thalidomide and prednisone appears effective
      in the treatment of CRPC, these agents are usually used after the occurrence of CRPC, not
      before. Thus, whether or not these patients should receive chemotherapy prior to development
      of CRPC, and whether this approach can prevent the aggressive progression of the disease to a
      treatment refractory status, remain largely open but intriguing questions.

      In this study, investigators performed a Phase I, single agent exploration, multicenter
      clinical trial to establish the treatment efficacy of several chemotherapeutic agents in
      patients with high risk localized prostate cancer who have developed the primary cancer in
      prostate. Up to 5 cohorts have been enrolled to determine the effectiveness and safety of
      single therapeutic strategy. Besides the five-year disease-free survival, overall survival
      and five-year metastasis-free survival post treatment, investigators also take into account
      the anticancer agent-induced tumor stroma damage extent, which may provide further evidence
      to support the treatment efficacy and assess the potential influence of a damaged tumor
      microenvironment on disease progression or regression in clinical settings.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Chemotherapy (single agent of CDMS) will be performed 45 days before surgery for patients who are diagnosed with prostate cancer without distant metastasis. The chemotherapy using CDMS will done for 4 cycles within 30 days after first diagnosis of prostate cancer.
primary purpose: Treatment
masking: Double (Participant, Care Provider)
masking description: Both the participants and care providers will be blind to the agents, but the investigators will be aware of and keep track of the whole regime and agents.
measure: 5 years disease-free survival
time frame: 5 years
description: There is no disease-associated progression during the 5 years post treatment (chemotherapy plus surgery).
measure: 5 years overall survival and metastasis-free survival
time frame: 5 years
description: The overall survival status and distant metastasis-free survival status during the 5 years post treatment (chemotherapy plus surgery).
arm group label: CDMS, Surgery
arm group type: Experimental
description: Preoperative chemotherapy using Cabazitaxel, Docetaxel, Mitoxantrone or Satraplatin (CDMS) as a single agent performed 45 days before surgery：Cabazitaxel 25 mg/m2, Docetaxel 35 mg/m2, Mitoxantrone 4 mg/m2 or Satraplatin 80 mg/m2, through intravenous (IV) or oral (Satraplatin) administration. IV or oral administration once every 7 days, totally 4 cycles. There is a 17-day interval between the last dose and surgery.
Procedure: radical prostatectomy surgery.
arm group label: Control
arm group type: No Intervention
description: No neoadjuvant chemotherapy using CDMS will be done for patients who are diagnosed with localized prostate cancer but subject to direct surgery to radically remove the primary tumor.
intervention type: Drug
intervention name: Cabazitaxel, Docetaxel, Mitoxantrone or Satraplatin
description: As preoperative neoadjuvant chemotherapy, drugss including Cabazitaxel, Docetaxel, Mitoxantrone or Satraplatin (CDMS) will be administered as a single agent performed 45 days before surgery：Cabazitaxel 25 mg/m2, Docetaxel 35 mg/m2, Mitoxantrone 4 mg/m2 or Satraplatin 80 mg/m2, through intravenous (IV) or oral (Satraplatin) administration. IV or oral administration once every 7 days, totally 4 cycles. There is a 17-day interval between the last dose and surgery.
arm group label: CDMS, Surgery
other name: Jevtana, Taxotere, Novantrone, JM216.
criteria: 
gender: Male
gender based: Yes
gender description: All participant patients should be male, adult.
minimum age: 40 Years
maximum age: 75 Years
healthy volunteers: No
last name: Yu Sun, Ph.D
role: Principal Investigator
affiliation: Shanghai Jiao Tong University School of Medicine
last name: Yu Sun, Ph.D
phone: 86-21-54923302
email: sunyu@sibs.ac.cn
last name: Weijun Ma, Ph.D
phone: 86-21-54923268
email: wjma@sibs.ac.cn
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Shanghai Jiao Tong University School of Medicine
investigator full name: Yu Sun
investigator title: Professor
mesh term: Prostatic Neoplasms
mesh term: Docetaxel
mesh term: Mitoxantrone
mesh term: Satraplatin
sharing ipd: No
ipd description: Investigators are happy to make individual participant data (IPD) available to other researchers upon request, as long as the data are not confidential and not restrained by the ethics policy.