<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/NCT01688492</url>
  </required_header>
  <id_info>
    <org_study_id>12-120</org_study_id>
    <nct_id>NCT01688492</nct_id>
  </id_info>
  <brief_title>Combining Ipilimumab With Abiraterone Acetate Plus Prednisone in Chemotherapy and Immunotherapy-naïve Patients With Progressive Metastatic Castration-resistant Prostate Cancer</brief_title>
  <official_title>A Phase 2 Study Combining Ipilimumab With Abiraterone Acetate Plus Prednisone in Chemotherapy and Immunotherapy-naïve Patients With Progressive Metastatic Castration-resistant Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Northwestern University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Oregon Health and Science University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Memorial Sloan Kettering Cancer Center</source>
  <brief_summary>
    <textblock>
      The purpose of this study is to find out what effects, good and/or bad, taking ipilimumab&#xD;
      with abiraterone acetate plus prednisone has on the patient and the prostate cancer.&#xD;
      Abiraterone acetate plus prednisone are drugs that lower testosterone (testosterone&#xD;
      stimulates prostate cancer growth). Abiraterone acetate plus prednisone is a treatment for&#xD;
      patients with prostate cancer.&#xD;
&#xD;
      Abiraterone acetate plus prednisone has not been used together with ipilimumab before. This&#xD;
      study will test how they work together. Each patient will receive abiraterone acetate,&#xD;
      prednisone and ipilimumab.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Anticipated">September 2024</completion_date>
  <primary_completion_date type="Anticipated">September 2024</primary_completion_date>
  <phase>Phase 1/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>safety (Phase I)</measure>
    <time_frame>2 years</time_frame>
    <description>AEs will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grading scale, version 4.0.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>progression-free survival (PFS) Phase II</measure>
    <time_frame>8 months</time_frame>
    <description>which is defined as the time from the start of therapy until the criteria for progression are met</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in PSA kinetics</measure>
    <time_frame>2 years</time_frame>
    <description>PSA levels will be assessed every 4 weeks during the Lead in Therapy, every 3 weeks during the Combination Therapy and every 4 weeks during the Maintenance Therapy. Outcomes will be reported both by the percent change in PSA from baseline and Week 21 (or earlier for those who discontinue therapy) and the maximum decline in PSA using a waterfall plot.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurable disease when present</measure>
    <time_frame>2 years</time_frame>
    <description>Measurable disease in viscera (liver or lung) is defined as per PCWG2 modified RECIST 1.1 as a lesion ≥10 mm in its longest diameter as measured with conventional techniques (ie, CT or MRI). For a lymph node to be considered measurable, the minimum diameter must be ≥20 mm in long axis when assessed by CT scan. All other lesions (or sites of disease) will be considered nonmeasurable disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate changes in radionuclide bone scan</measure>
    <time_frame>2 years</time_frame>
    <description>Radionucleotide bone scan outcome should be recorded as either new lesions or no new lesions. On bone scan, progression of bone metastases is defined as the appearance of 2 or more new bone lesions compared to the baseline scan. In the case of the first Week 8 and Week 16 assessment scans a confirmatory scan performed 6 weeks later needs to shows 2 or more additional new lesions (for a total of at least 4 new lesions seen since baseline) for progression to be documented (the date of progression is always the date of the first scan showing the change).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">57</enrollment>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>ipilimumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This multi-institution open label study has a Phase 1 and Phase 2 component. The Phase 1 dose escalation stage is to establish the tolerability of ipilimumab to be used in combination with the standard clinical dose of abiraterone acetate plus prednisone in chemotherapy and immunotherapy-naïve patients with progressive metastatic CRPC. Due to the overlapping potential hepatic toxicity between abiraterone and ipilimumab, a Lead in Therapy with abiraterone plus prednisone for 2 cycles will assess for adverse events related to the abiraterone plus prednisone. Patients, who tolerate well the Lead in therapy as defined by Grade 1 or less AEs, will pursue Combination Therapy. Patients with AEs Grade ≥ 2 after Lead in Therapy will be excluded and replaced. The Phase 2 stage will assess efficacy and confirm an acceptable safety profile of the recommended dose.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ipilimumab</intervention_name>
    <description>Abiraterone acetate (JanssenBiotech, Inc/Johnson &amp; Johnson) 1000 mg orally daily plus prednisone 5 mg orally twice daily will be administered continuously during the duration of the trial. Starting at cycle 3 (Combination Therapy), Ipilimumab (Bristol-Myers Squibb) will be infused intravenously (IV) once every 3 weeks for a total of 4 infusions.</description>
    <arm_group_label>ipilimumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Chemotherapy- and immunotherapy-naïve patients with progressive metastatic CRPC are&#xD;
        eligible.&#xD;
&#xD;
          -  Age 18 or older, and be willing and able to provide informed consent.&#xD;
&#xD;
          -  Histologically or cytologically confirmed adenocarcinoma of the prostate at either&#xD;
             MSKCC or at the participating site.&#xD;
&#xD;
          -  Castrate serum testosterone level, ≤ 1.73 nmol/L (50 ng/dL), at the Screening visit.&#xD;
&#xD;
          -  Ongoing androgen deprivation therapy with a GnRH analogue or bilateral orchiectomy&#xD;
             (ie, surgical or medical castration).&#xD;
&#xD;
          -  Metastatic disease on imaging (e.g., bone scan, CT, MRI). Patients whose disease&#xD;
             spread is limited to regional pelvic lymph nodes are not eligible. If lymph node&#xD;
             metastasis is the only evidence of metastasis, it must be ≥ 2 cm in diameter.&#xD;
&#xD;
          -  Progressive disease at study entry defined by PSA and/or radiographic criteria&#xD;
             according to the PCWG2.&#xD;
&#xD;
          -  Karnofsky performance status of ≥80-100, and estimated life expectancy of ≥ 6 months.&#xD;
&#xD;
          -  Toxicities related to prior therapy must either have returned to ≤ Grade 1 or baseline&#xD;
             or been deemed irreversible and in the opinion of the Investigator not worsened.&#xD;
&#xD;
          -  Able to swallow the study drug and comply with study requirements.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of another malignancy within the previous 5 years other than nonmelanomatous&#xD;
             skin cancer.&#xD;
&#xD;
          -  Absolute neutrophil count &lt; 1,500/μL, or platelet count &lt; 75,000/μL, or hemoglobin &lt;&#xD;
             5.6 mmol/L (9 g/dL) at the Screening visit. (NOTE: patients may not have received any&#xD;
             growth factors within 7 days or blood transfusions within 28 days of the hematologic&#xD;
             laboratory values obtained at the Screening visit).&#xD;
&#xD;
          -  Serum bilirubin ≥ 1.5 x ULN or for patients with Gilbert's disease, ≥3 mg/dL at the&#xD;
             Screening visit; AST or ALT ≥ 2.5 x ULN, (for patients with known liver metastasis,&#xD;
             AST or ALT ≤ 5 x ULN is allowed) at the Screening visit.&#xD;
&#xD;
          -  Creatinine &gt; 177 μmol/L (2 mg/dL), albumin &lt; 30 g/L (3.0 g/dL), potassium ≤ 3.5 mEq/L&#xD;
             at the Screening visit.&#xD;
&#xD;
          -  Clinically significant cardiovascular disease including myocardial infarction within 6&#xD;
             months, uncontrolled angina within 3 months, congestive heart failure New York Heart&#xD;
             Association (NYHA) class 3 or 4, uncontrolled hypertension as indicated by systolic&#xD;
             blood pressure &gt; 160 mmHg or diastolic blood pressure &gt; 95 mmHg at the Screening&#xD;
             visit.&#xD;
&#xD;
          -  Major surgery or radiation therapy within 4 weeks of enrollment (Day 1 Visit).&#xD;
&#xD;
          -  Treatment with antiandrogens (eg, bicalutamide, flutamide, or nilutamide) within 4&#xD;
             weeks of enrollment (Day 1 visit). Concomitant therapy with any of the agents listed&#xD;
             in Section 4.3.2 is prohibited.&#xD;
&#xD;
          -  History of progression of prostate cancer disease while receiving ketoconazole. Prior&#xD;
             use or participation in a clinical trial of an investigational agent that blocks&#xD;
             androgen synthesis (eg, abiraterone acetate, TAK-700, TAK-683, TAK-448), chemotherapy,&#xD;
             or immunological agents (eg, immune modulators, cytokines, vaccines, or&#xD;
             antibody-delivered chemotherapy). The use of denosumab for bone metastasis is&#xD;
             permitted.&#xD;
&#xD;
          -  Known allergy to any of the compounds under investigation.&#xD;
&#xD;
          -  The patient has uncontrolled or significant medical condition other than cancer, that&#xD;
             would prevent the participation in the study or make this protocol unreasonably&#xD;
             hazardous, in the opinion of the investigator, including but not limited to:&#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 (eg,&#xD;
             Guillain-Barre syndrome and myasthenia gravis).&#xD;
&#xD;
          -  Known or suspected brain metastasis, or untreated leptomeningeal disease.&#xD;
&#xD;
          -  Active infection or other medical condition that would make prednisone use&#xD;
             contraindicated.&#xD;
&#xD;
          -  Active or symptomatic viral hepatitis or chronic liver disease.&#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>Daniel C. Danila, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Evanston</city>
        <state>Illinois</state>
        <zip>60208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mskcc.org/</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>September 14, 2012</study_first_submitted>
  <study_first_submitted_qc>September 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 20, 2012</study_first_posted>
  <last_update_submitted>September 11, 2023</last_update_submitted>
  <last_update_submitted_qc>September 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>MDX-010 (Ipilimumab)</keyword>
  <keyword>ABIRATERONE ACETATE (CB 7630)</keyword>
  <keyword>PREDNISONE</keyword>
  <keyword>Immunotherapy-naïve</keyword>
  <keyword>castration resistant prostate cancer (CRPC)</keyword>
  <keyword>12-120</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>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/NCT01688492
org study id: 12-120
nct id: NCT01688492
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
The purpose of this study is to find out what effects, good and/or bad, taking ipilimumab
      with abiraterone acetate plus prednisone has on the patient and the prostate cancer.
      Abiraterone acetate plus prednisone are drugs that lower testosterone (testosterone
      stimulates prostate cancer growth). Abiraterone acetate plus prednisone is a treatment for
      patients with prostate cancer.

      Abiraterone acetate plus prednisone has not been used together with ipilimumab before. This
      study will test how they work together. Each patient will receive abiraterone acetate,
      prednisone and ipilimumab.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: safety (Phase I)
time frame: 2 years
description: AEs will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grading scale, version 4.0.
measure: progression-free survival (PFS) Phase II
time frame: 8 months
description: which is defined as the time from the start of therapy until the criteria for progression are met
measure: Changes in PSA kinetics
time frame: 2 years
description: PSA levels will be assessed every 4 weeks during the Lead in Therapy, every 3 weeks during the Combination Therapy and every 4 weeks during the Maintenance Therapy. Outcomes will be reported both by the percent change in PSA from baseline and Week 21 (or earlier for those who discontinue therapy) and the maximum decline in PSA using a waterfall plot.
measure: Measurable disease when present
time frame: 2 years
description: Measurable disease in viscera (liver or lung) is defined as per PCWG2 modified RECIST 1.1 as a lesion ≥10 mm in its longest diameter as measured with conventional techniques (ie, CT or MRI). For a lymph node to be considered measurable, the minimum diameter must be ≥20 mm in long axis when assessed by CT scan. All other lesions (or sites of disease) will be considered nonmeasurable disease.
measure: Evaluate changes in radionuclide bone scan
time frame: 2 years
description: Radionucleotide bone scan outcome should be recorded as either new lesions or no new lesions. On bone scan, progression of bone metastases is defined as the appearance of 2 or more new bone lesions compared to the baseline scan. In the case of the first Week 8 and Week 16 assessment scans a confirmatory scan performed 6 weeks later needs to shows 2 or more additional new lesions (for a total of at least 4 new lesions seen since baseline) for progression to be documented (the date of progression is always the date of the first scan showing the change).
arm group label: ipilimumab
arm group type: Experimental
description: This multi-institution open label study has a Phase 1 and Phase 2 component. The Phase 1 dose escalation stage is to establish the tolerability of ipilimumab to be used in combination with the standard clinical dose of abiraterone acetate plus prednisone in chemotherapy and immunotherapy-naïve patients with progressive metastatic CRPC. Due to the overlapping potential hepatic toxicity between abiraterone and ipilimumab, a Lead in Therapy with abiraterone plus prednisone for 2 cycles will assess for adverse events related to the abiraterone plus prednisone. Patients, who tolerate well the Lead in therapy as defined by Grade 1 or less AEs, will pursue Combination Therapy. Patients with AEs Grade ≥ 2 after Lead in Therapy will be excluded and replaced. The Phase 2 stage will assess efficacy and confirm an acceptable safety profile of the recommended dose.
intervention type: Drug
intervention name: Ipilimumab
description: Abiraterone acetate (JanssenBiotech, Inc/Johnson & Johnson) 1000 mg orally daily plus prednisone 5 mg orally twice daily will be administered continuously during the duration of the trial. Starting at cycle 3 (Combination Therapy), Ipilimumab (Bristol-Myers Squibb) will be infused intravenously (IV) once every 3 weeks for a total of 4 infusions.
arm group label: ipilimumab
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Daniel C. Danila, MD
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
facility: 
facility: 
facility: 
country: United States
url: http://www.mskcc.org/
description: Memorial Sloan Kettering Cancer Center
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Ipilimumab