<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/NCT04475016</url>
  </required_header>
  <id_info>
    <org_study_id>B2020-103-01</org_study_id>
    <nct_id>NCT04475016</nct_id>
  </id_info>
  <brief_title>TIP (Paclitaxel + Ifosfamide + Cisplatin) Combined With Nimotuzumab &amp; Triprilimab as Neoadjuvant Treatment in Locally Advanced Penile Cancer</brief_title>
  <official_title>A Single Center and Single Arm Study of TIP (Paclitaxel + Ifosfamide + Cisplatin) Combined With Nimotuzumab &amp; Triprilimab as Neoadjuvant Treatment in Locally Advanced Penile Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sun Yat-sen University</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>
      Primary Objective:To evaluate the efficacy and safety of TIP (paclitaxel + ifosfamide +&#xD;
      cisplatin) combined with nimotuzumab &amp; triprilimab as neoadjuvant treatment in locally&#xD;
      advanced penile cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Penile cancer is a rare malignant tumor, which often occurs in the inner plate of prepuce and&#xD;
      glans. Squamous cell carcinoma is the most common pathological type. Lymph node metastasis is&#xD;
      a crucial factor that leads to poor prognosis of penile cancer. The 5-year OS of penile&#xD;
      cancer patients without lymph node metastasis is 90%. Still, it goes down sharply in patients&#xD;
      with inguinal lymph node metastasis and pelvic lymph node metastasis, which is 50% and 0%,&#xD;
      respectively.&#xD;
&#xD;
      Using neoadjuvant chemotherapy to treat patients with locally advanced penile cancer (T4, any&#xD;
      N stage, or any T stage, N3) may improve their prognosis. TIP (Paclitaxel + Ifosfamide +&#xD;
      Cisplatin) regimen is the first line neoadjuvant treatment recommended by NCCN guidelines.&#xD;
      Epidermal growth factor receptor (EGFR) plays a vital role in the development of penile&#xD;
      cancer. It's also an important therapeutic target for penile cancer. PD-1 is an immune&#xD;
      checkpoint molecule on the surface of T cells. In recent years, immune-checkpoint inhibitors&#xD;
      targeting PD-1 have shown good efficacy in a variety of tumors. Some phase II / III clinical&#xD;
      trials have shown that PD-1 inhibitors can improve the prognosis of patients with lung&#xD;
      squamous cell carcinoma, head and neck squamous cell carcinoma and cervical cancer. Previous&#xD;
      studies have found that PD-L1 is highly expressed in 40% - 60% of penile cancer, suggesting&#xD;
      that penile cancer patients may benefit from immunotherapy.&#xD;
&#xD;
      The management of penile cancer with lymph node metastasis is difficult, especially for N2-3&#xD;
      stage. This phase II study aim to explore an effective combination therapy for locally&#xD;
      advanced penile cancer. 29 patients need to be enrolled.TIP &amp; nimotuzumab &amp; triprilimab will&#xD;
      be administered per 21-day until surgery, evidence of disease progression or onset of&#xD;
      unacceptable toxicity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 12, 2020</start_date>
  <completion_date type="Actual">May 30, 2022</completion_date>
  <primary_completion_date type="Actual">May 6, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With Pathologically Complete Response</measure>
    <time_frame>12 weeks</time_frame>
    <description>Histopathologic assessment for patients undergoing surgical resection followed by 4 cycles of neoadjuvant treatment. Pathologically complete response is defined as the absence of noninvasive tumor residuals in inguinal lymph node and pelvic lymph node after neoadjuvant chemotherapy as assessed by American Joint Committee on Cancer (AJCC) staging version 8.0.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>6 weeks</time_frame>
    <description>ORR is defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>2 months</time_frame>
    <description>Progression free survival is defined as the time from the randomization to tumor progression or death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>6 months</time_frame>
    <description>Overall survival is defined as the time from randomization to death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>2-months</time_frame>
    <description>Number of participants with treatment-related adverse events as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>Penile Cancer</condition>
  <arm_group>
    <arm_group_label>Neoadjuvant Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TIP (Paclitaxel + Ifosfamide + Cisplatin) &amp; Nimotuzumab &amp; Triprilimab</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Albumin-Bound Paclitaxel</intervention_name>
    <description>260 mg/m² IV over 30 minutes on Day 1</description>
    <arm_group_label>Neoadjuvant Therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ifosfamide</intervention_name>
    <description>1200 mg/m² IV over 2 hours on Days 1-3</description>
    <arm_group_label>Neoadjuvant Therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>25 mg/m² IV over 2 hours on Days 1-3</description>
    <arm_group_label>Neoadjuvant Therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nimotuzumab</intervention_name>
    <description>400 mg IV on Day 1</description>
    <arm_group_label>Neoadjuvant Therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Triprilimab</intervention_name>
    <description>240 mg IV on Day 1</description>
    <arm_group_label>Neoadjuvant Therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Squamous cell carcinoma confirmed by histology or cytology;&#xD;
&#xD;
          2. Clinical Stage is Locally advanced penile cancer (T4, any N stage; or any T stage,&#xD;
             N3);&#xD;
&#xD;
          3. No prior chemotherapy for newly diagnosed or relapsed patients;&#xD;
&#xD;
          4. There is at least one measurable lesion according to the solid tumor efficacy&#xD;
             evaluation standard RECIST1.1;&#xD;
&#xD;
          5. the Eastern Cooperative Oncology Group (ECOG) scored 0-2;&#xD;
&#xD;
          6. Blood marrow function: Hemoglobin(Hb) &gt;/= 80g/L; White blood cell count &gt;/=&#xD;
             3.0x10^9/L; Neutrophil count &gt;/= 1.5x10^9/L; Platelet count &gt;/= 100x10^9/L;&#xD;
&#xD;
          7. Liver function: AST, ALT, ALP &lt;/= 2.5 ULN; Total bilirubin &lt;/= 1.5 ULN;&#xD;
&#xD;
          8. Estimated survival &gt;/= 12 months;&#xD;
&#xD;
          9. No prior serious disease history of systemic organ;&#xD;
&#xD;
         10. The participant unterstand this study procedure and sign the informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Peripheral neuropathy degree &gt;/=2 (affecting patient's function);&#xD;
&#xD;
          2. Previously received any other experimental drug treatment within 4 weeks before&#xD;
             enrollment;&#xD;
&#xD;
          3. Patients with other cancer at present, or have other malignent tumor history within&#xD;
             past 5 years. Except for: (1) Cured skin non-malignant melanoma; (2) Curable tumor,&#xD;
             including low-risk prostate cancer (T1a, Gleason score&lt;6, PSA&lt;0.5ng/ml), superficial&#xD;
             bladder cancer and so on; (3) Other solid tumors have received radical treatment, and&#xD;
             no recurrence or metastasis has been found at least 5 years;&#xD;
&#xD;
          4. Other serious or poorly controlled concomitant diseases, including but not limited to:&#xD;
             (1) Severe or acute attack disease history of cardiovascular, liver, respiratory,&#xD;
             kidney, blood ,endocrine or neuropsychiatric system within 6 months; (2) Active&#xD;
             infection history and needed antibiotic treatment within 2 weeks before enrollment;&#xD;
             (3) Congestive heart failure (grade III-IV); (4) Unstable angina pectoris or&#xD;
             myocardial infarction history within 6 months.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Sun Yat-sen University Cancer Center</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 17, 2020</study_first_posted>
  <last_update_submitted>June 8, 2022</last_update_submitted>
  <last_update_submitted_qc>June 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>ZHOU FANGJIAN</investigator_full_name>
    <investigator_title>Director</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Penile Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Ifosfamide</mesh_term>
    <mesh_term>Albumin-Bound Paclitaxel</mesh_term>
    <mesh_term>Nimotuzumab</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/NCT04475016
org study id: B2020-103-01
nct id: NCT04475016
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Primary Objective:To evaluate the efficacy and safety of TIP (paclitaxel + ifosfamide +
      cisplatin) combined with nimotuzumab & triprilimab as neoadjuvant treatment in locally
      advanced penile cancer.
Penile cancer is a rare malignant tumor, which often occurs in the inner plate of prepuce and
      glans. Squamous cell carcinoma is the most common pathological type. Lymph node metastasis is
      a crucial factor that leads to poor prognosis of penile cancer. The 5-year OS of penile
      cancer patients without lymph node metastasis is 90%. Still, it goes down sharply in patients
      with inguinal lymph node metastasis and pelvic lymph node metastasis, which is 50% and 0%,
      respectively.

      Using neoadjuvant chemotherapy to treat patients with locally advanced penile cancer (T4, any
      N stage, or any T stage, N3) may improve their prognosis. TIP (Paclitaxel + Ifosfamide +
      Cisplatin) regimen is the first line neoadjuvant treatment recommended by NCCN guidelines.
      Epidermal growth factor receptor (EGFR) plays a vital role in the development of penile
      cancer. It's also an important therapeutic target for penile cancer. PD-1 is an immune
      checkpoint molecule on the surface of T cells. In recent years, immune-checkpoint inhibitors
      targeting PD-1 have shown good efficacy in a variety of tumors. Some phase II / III clinical
      trials have shown that PD-1 inhibitors can improve the prognosis of patients with lung
      squamous cell carcinoma, head and neck squamous cell carcinoma and cervical cancer. Previous
      studies have found that PD-L1 is highly expressed in 40% - 60% of penile cancer, suggesting
      that penile cancer patients may benefit from immunotherapy.

      The management of penile cancer with lymph node metastasis is difficult, especially for N2-3
      stage. This phase II study aim to explore an effective combination therapy for locally
      advanced penile cancer. 29 patients need to be enrolled.TIP & nimotuzumab & triprilimab will
      be administered per 21-day until surgery, evidence of disease progression or onset of
      unacceptable toxicity.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With Pathologically Complete Response
time frame: 12 weeks
description: Histopathologic assessment for patients undergoing surgical resection followed by 4 cycles of neoadjuvant treatment. Pathologically complete response is defined as the absence of noninvasive tumor residuals in inguinal lymph node and pelvic lymph node after neoadjuvant chemotherapy as assessed by American Joint Committee on Cancer (AJCC) staging version 8.0.
measure: Objective Response Rate (ORR)
time frame: 6 weeks
description: ORR is defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
measure: Progression Free Survival (PFS)
time frame: 2 months
description: Progression free survival is defined as the time from the randomization to tumor progression or death due to any cause.
measure: Overall Survival (OS)
time frame: 6 months
description: Overall survival is defined as the time from randomization to death due to any cause.
measure: Adverse events
time frame: 2-months
description: Number of participants with treatment-related adverse events as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0.
arm group label: Neoadjuvant Therapy
arm group type: Experimental
description: TIP (Paclitaxel + Ifosfamide + Cisplatin) & Nimotuzumab & Triprilimab
intervention type: Drug
intervention name: Albumin-Bound Paclitaxel
description: 260 mg/m² IV over 30 minutes on Day 1
arm group label: Neoadjuvant Therapy
intervention type: Drug
intervention name: Ifosfamide
description: 1200 mg/m² IV over 2 hours on Days 1-3
arm group label: Neoadjuvant Therapy
intervention type: Drug
intervention name: Cisplatin
description: 25 mg/m² IV over 2 hours on Days 1-3
arm group label: Neoadjuvant Therapy
intervention type: Drug
intervention name: Nimotuzumab
description: 400 mg IV on Day 1
arm group label: Neoadjuvant Therapy
intervention type: Drug
intervention name: Triprilimab
description: 240 mg IV on Day 1
arm group label: Neoadjuvant Therapy
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: ZHOU FANGJIAN
investigator title: Director
mesh term: Penile Neoplasms
mesh term: Paclitaxel
mesh term: Ifosfamide
mesh term: Albumin-Bound Paclitaxel
mesh term: Nimotuzumab