<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/NCT01676649</url>
  </required_header>
  <id_info>
    <org_study_id>CA184-195</org_study_id>
    <nct_id>NCT01676649</nct_id>
  </id_info>
  <brief_title>Ipilimumab With Carboplatin and Paclitaxel in Patients With Unresectable Stage III and Stage IV Melanoma</brief_title>
  <official_title>A Phase II Study of Ipilimumab in Combination With Carboplatin and Paclitaxel in Patients With Unresectable Stage III or Stage IV Melanoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jewish General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jewish General Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The safety of the combination of ipilimumab with carboplatin/paclitaxel treatment with two&#xD;
      different dosing schedules will be investigated in patients with metastatic melanoma. This&#xD;
      protocol will also investigate both the clinical benefit of this combination and the features&#xD;
      of the host immune system that may predict response to ipilimumab with chemotherapy in&#xD;
      patients with unresectable Stage III and Stage IV melanoma.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Anticipated">May 2026</completion_date>
  <primary_completion_date type="Actual">February 2017</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>Safety: Incidence of adverse events</measure>
    <time_frame>24 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Putative Early Cellular and/or Molecular Biomarker levels</measure>
    <time_frame>27 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine ORR and clinical benefit rate (ORR + SD ≥ 24 weeks), by immune related response criteria (irRC) and modified WHO criteria (mWHO) of ipilimumab when given with carboplatin and paclitaxel at two different dosing regimens.</measure>
    <time_frame>48 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine the overall survival (OS) of patients receiving ipilimumab with carboplatin and paclitaxel.</measure>
    <time_frame>48 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine progression free survival (PFS) per irRC and mWHO of patients receiving ipilimumab with carboplatin and paclitaxel.</measure>
    <time_frame>48 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Untreated Stage III Melanoma or Stage IV Melanoma</condition>
  <arm_group>
    <arm_group_label>A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm A: Carboplatin (week 1, week 4, week 7, week 10, and week 13) Paclitaxel (week 1, week 4, week 7, week 10, and week 13) Ipilimumab (week 4, week 7, week 10, and week 13)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Carboplatin (week 1, week 4, week 7, week 10, and week 13) Paclitaxel (week 1, week 4, week 7, week 10, and week 13) Ipilimumab (week 5, week 8, week 11, and week 14)</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Ipilimumab</intervention_name>
    <description>3 mg/kg</description>
    <arm_group_label>A</arm_group_label>
    <arm_group_label>B</arm_group_label>
    <other_name>YERVOY</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>AUC = 6</description>
    <arm_group_label>A</arm_group_label>
    <arm_group_label>B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>175 mg/m2</description>
    <arm_group_label>A</arm_group_label>
    <arm_group_label>B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Willing and able to give written informed consent.&#xD;
&#xD;
          -  Histologic diagnosis of malignant melanoma&#xD;
&#xD;
          -  Untreated unresectable Stage III melanoma with N3 macroscopic lymph nodes or&#xD;
             in-transit/satellite metastases or Stage IV melanoma (note that prior adjuvant&#xD;
             melanoma therapy is permitted). Prior treatment with BRAF inhibitors in the metastatic&#xD;
             setting is also permitted.&#xD;
&#xD;
          -  Measurable/evaluable disease&#xD;
&#xD;
          -  Required values for initial laboratory tests:&#xD;
&#xD;
               -  WBC ≥ 2000/uL&#xD;
&#xD;
               -  ANC ≥ 1.5 x 10E9/L&#xD;
&#xD;
               -  Platelets ≥ 100 x 10E9/L&#xD;
&#xD;
               -  Hemoglobin ≥ 90 g/L (may be transfused)&#xD;
&#xD;
               -  Creatinine Clearance ≥ 50 ml/min (calculated -Cockcroft-Gault)&#xD;
&#xD;
               -  AST/ALT ≤ 2.5 x ULN for patients without liver metastasis,&#xD;
&#xD;
                  ≤ 5 times for liver metastases&#xD;
&#xD;
               -  Bilirubin ≤ 2.5 x ULN&#xD;
&#xD;
          -  No active or chronic infection with HIV, Hepatitis B, or Hepatitis C.&#xD;
&#xD;
          -  ECOG Performance status of 0 or 1.&#xD;
&#xD;
          -  Men and women, ≥ 18 years of age. Women of childbearing potential (WOCBP) must be&#xD;
             using an adequate method of contraception to avoid pregnancy throughout the study and&#xD;
             for up to 26 weeks after the last dose of investigational product, in such a manner&#xD;
             that the risk of pregnancy is minimized.&#xD;
&#xD;
        WOCBP include any female who has experienced menarche and who has not undergone successful&#xD;
        surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy)&#xD;
        or is not post-menopausal. Post-menopause is defined as:&#xD;
&#xD;
          -  Amenorrhea ≥ 12 consecutive months without another cause, or&#xD;
&#xD;
          -  For women with irregular menstrual periods and taking hormone replacement therapy&#xD;
             (HRT), a documented serum follicle stimulating hormone (FSH) level ≥ 35 U/L. WOCBP&#xD;
             must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or&#xD;
             equivalent units of HCG) within 72 hours before the start of ipilimumab.&#xD;
&#xD;
        Men of fathering potential must be using an adequate method of contraception to avoid&#xD;
        conception throughout the study [and for up to 26 weeks after the last doseof&#xD;
        investigational product] in such a manner that the risk of pregnancy is minimized.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence of symptomatic CNS lesions as determined by the investigator (patients with&#xD;
             asymptomatic lesions or previously irradiated or surgically resected are eligible).&#xD;
&#xD;
          -  Any other malignancy from which the patient has been disease-free for less than one&#xD;
             year, with the exception of adequately treated basal or squamous cell skin cancer,&#xD;
             superficial bladder cancer or carcinoma in situ of the cervix.&#xD;
&#xD;
          -  Autoimmune disease: Patients with a history of inflammatory bowel disease, including&#xD;
             ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients&#xD;
             with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive&#xD;
             sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg,&#xD;
             Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g.&#xD;
             Guillain-Barre Syndrome and Myasthenia Gravis).&#xD;
&#xD;
          -  Any underlying medical or psychiatric condition, which in the opinion of the&#xD;
             investigator will make the administration of ipilimumab hazardous or obscure the&#xD;
             interpretation of AEs, such as a condition associated with frequent diarrhea.&#xD;
&#xD;
          -  Patients with ≥ Grade 2 peripheral neuropathy.&#xD;
&#xD;
          -  Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to&#xD;
             1 month before or after any dose of ipilimumab).&#xD;
&#xD;
          -  A history of prior treatment with ipilimumab or prior CD137 agonist or CTLA 4&#xD;
             inhibitor or agonist.&#xD;
&#xD;
          -  Concomitant therapy with any of the following: IL 2, interferon, or other non-study&#xD;
             immunotherapy regimens; immunosuppressive agents; other investigation therapies; or&#xD;
             chronic use of systemic corticosteroids.&#xD;
&#xD;
          -  Women of childbearing potential (WOCBP), defined above, who:&#xD;
&#xD;
               1. are unwilling or unable to use an acceptable method of contraception to avoid&#xD;
                  pregnancy for their entire study period and for at least 26 weeks after cessation&#xD;
                  of study drug, or&#xD;
&#xD;
               2. have a positive pregnancy test at baseline, or&#xD;
&#xD;
               3. are pregnant or breastfeeding.&#xD;
&#xD;
          -  Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for&#xD;
             treatment of either a psychiatric or physical (eg, infectious) illness.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wilson Miller, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Jewish General Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rahima Jamal, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Notre-Dame Hospital (CHUM)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Jewish General Hospital</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3T 1E2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>August 29, 2012</study_first_submitted>
  <study_first_submitted_qc>August 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 31, 2012</study_first_posted>
  <last_update_submitted>February 17, 2021</last_update_submitted>
  <last_update_submitted_qc>February 17, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 18, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Jewish General Hospital</investigator_affiliation>
    <investigator_full_name>Wilson Miller</investigator_full_name>
    <investigator_title>Medical Oncologist</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Ipilimumab</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/NCT01676649
org study id: CA184-195
nct id: NCT01676649
lead sponsor: 
has dmc: No
The safety of the combination of ipilimumab with carboplatin/paclitaxel treatment with two
      different dosing schedules will be investigated in patients with metastatic melanoma. This
      protocol will also investigate both the clinical benefit of this combination and the features
      of the host immune system that may predict response to ipilimumab with chemotherapy in
      patients with unresectable Stage III and Stage IV melanoma.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety: Incidence of adverse events
time frame: 24 months
measure: Putative Early Cellular and/or Molecular Biomarker levels
time frame: 27 months
measure: To determine ORR and clinical benefit rate (ORR + SD ≥ 24 weeks), by immune related response criteria (irRC) and modified WHO criteria (mWHO) of ipilimumab when given with carboplatin and paclitaxel at two different dosing regimens.
time frame: 48 months
measure: To determine the overall survival (OS) of patients receiving ipilimumab with carboplatin and paclitaxel.
time frame: 48 months
measure: To determine progression free survival (PFS) per irRC and mWHO of patients receiving ipilimumab with carboplatin and paclitaxel.
time frame: 48 months
arm group label: A
arm group type: Experimental
description: Arm A: Carboplatin (week 1, week 4, week 7, week 10, and week 13) Paclitaxel (week 1, week 4, week 7, week 10, and week 13) Ipilimumab (week 4, week 7, week 10, and week 13)
arm group label: B
arm group type: Experimental
description: Carboplatin (week 1, week 4, week 7, week 10, and week 13) Paclitaxel (week 1, week 4, week 7, week 10, and week 13) Ipilimumab (week 5, week 8, week 11, and week 14)
intervention type: Biological
intervention name: Ipilimumab
description: 3 mg/kg
arm group label: A
arm group label: B
other name: YERVOY
intervention type: Drug
intervention name: Carboplatin
description: AUC = 6
arm group label: A
arm group label: B
intervention type: Drug
intervention name: Paclitaxel
description: 175 mg/m2
arm group label: A
arm group label: B
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Wilson Miller, MD, PhD
role: Principal Investigator
affiliation: Jewish General Hospital
last name: Rahima Jamal, MD
role: Principal Investigator
affiliation: Notre-Dame Hospital (CHUM)
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Jewish General Hospital
investigator full name: Wilson Miller
investigator title: Medical Oncologist
mesh term: Melanoma
mesh term: Paclitaxel
mesh term: Carboplatin
mesh term: Ipilimumab