<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/NCT04457284</url>
  </required_header>
  <id_info>
    <org_study_id>20-202</org_study_id>
    <nct_id>NCT04457284</nct_id>
  </id_info>
  <brief_title>Temozolomide, Cisplatin, and Nivolumab in People With Colorectal Cancer</brief_title>
  <official_title>A Phase II Study of Temozolomide, Cisplatin and Nivolumab in MMR-Proficient Colorectal 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>
  </sponsors>
  <source>Memorial Sloan Kettering Cancer Center</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will test whether the combination of cisplatin, nivolumab, and temozolomide is an&#xD;
      effective treatment for in people with advanced and/or metastatic colorectal cancer that is&#xD;
      mismatch repair-proficient (MMR-proficient). The researchers will also look at how safe the&#xD;
      study drug combination is in participants.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 18, 2020</start_date>
  <completion_date type="Anticipated">July 2025</completion_date>
  <primary_completion_date type="Anticipated">July 2025</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>This will be a two-stage design, single arm, phase II study.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Response</measure>
    <time_frame>1 year</time_frame>
    <description>will be evaluated in this study using the new international criteria proposed in RECIST 1.1 [Eur J Ca 45:228-247, 2009]. Changes in the largest diameter (unidimensional measurement) of the tumor and the shortest diameter of malignant lymph nodes are used with the RECIST criteria.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Colorectal Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>temozolomide, cisplatin and nivolumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive oral TMZ at 150-200 mg/m2 day 1 to 5 every 4 weeks, cisplatin via IV infusion at 40 mg/m2 every two weeks (Q2W), and nivolumab via IV infusion at 480 mg every four weeks (Q4W).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Temozolomide (TMZ)</intervention_name>
    <description>TMZ 150 mg/m2 Day 1 - 5 Q4W PO Cycle 1&#xD;
TMZ 200 mg/m2 Day 1 - 5 Q4W PO Cycle 2 +</description>
    <arm_group_label>temozolomide, cisplatin and nivolumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Cisplatin 40 mg/m2 Q2W IV infusion Cycle 1 +</description>
    <arm_group_label>temozolomide, cisplatin and nivolumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Nivolumab 480 mg Q4W IV infusion Cycle 1 +</description>
    <arm_group_label>temozolomide, cisplatin and nivolumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject or legally authorized representative is willing and able to provide written&#xD;
             informed consent/assent for the trial.&#xD;
&#xD;
          -  Histologically- or cytologically- confirmed colorectal adenocarcinoma.&#xD;
&#xD;
          -  Locally advanced unresectable or metastatic CRC.&#xD;
&#xD;
          -  Undergone testing for MSI/dMMR and determined to be MSS or MMR proficient.&#xD;
&#xD;
          -  Undergone testing for BRAF and POLE and determined to be wild type.&#xD;
&#xD;
          -  Subjects must be refractory to, or intolerant of, at least 2 lines of standard&#xD;
             chemotherapy, according to NCCN guidelines for patients eligible for intensive&#xD;
             therapy, or have received prior FOLFOXIRI. Patients are considered refractory if&#xD;
             progressed within 3 months of last dose, or within 6 months of completing adjuvant&#xD;
             FOLFOX/CAPEOX. At a minimum, such therapies should include oxaliplatin, irinotecan and&#xD;
             a fluoropyrimidine.&#xD;
&#xD;
          -  At least one index lesion which is measurable based on RECIST 1.1.&#xD;
&#xD;
          -  Be ≥ 18 years of age on day of signing informed consent.&#xD;
&#xD;
          -  Consent for use of archival tissue and blood draws for research purposes.&#xD;
&#xD;
          -  Have an ECOG performance status of 0 or 1.&#xD;
&#xD;
          -  Demonstrate adequate organ function as defined in Table 6.1, all screening labs should&#xD;
             be performed within 28 days of treatment initiation.&#xD;
&#xD;
          -  Adequate organ function, defined as:&#xD;
&#xD;
               -  Absolute Neutrophil Count ≥ 1,500/mcL.&#xD;
&#xD;
               -  Platelet count ≥ 100,000/mcL.&#xD;
&#xD;
               -  Serum creatinine ≤ 1.5 x ULN or CrCl ≥60 mL/min for subjects with creatinine&#xD;
                  levels &gt;1.5 ULN.&#xD;
&#xD;
               -  WBC ≥ 2000/μL&#xD;
&#xD;
               -  Hemoglobin ≥ 9.0 g/dL&#xD;
&#xD;
               -  AST and ALT ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with liver metastases.&#xD;
&#xD;
               -  Bilirubin ≤ 1.5 × ULN or Direct bilirubin ≤ ULN for subjects with bilirubin&#xD;
                  levels &gt;1.5&#xD;
&#xD;
               -  INR/PT and PTT ≤1.5 X ULN unless on anticoagulant therapy and PT/PTT within&#xD;
                  therapeutic range.&#xD;
&#xD;
        aCreatinine clearance should be calculated per institutional standard.&#xD;
&#xD;
          -  Adequate method of contraception.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject is currently participating in or has participated in a study of an&#xD;
             investigational agent or using an investigational device within 4 weeks of the first&#xD;
             dose of treatment.&#xD;
&#xD;
          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (&gt;10&#xD;
             mg/day prednisone, or equivalent) or any other form of immunosuppressive therapy&#xD;
             within 7 days prior to the first dose of trial treatment. Inhaled or topical steroids&#xD;
             are permitted in the absence of active autoimmune disease&#xD;
&#xD;
          -  Prior chemotherapy, targeted small molecule therapy, or biological therapy, within 2&#xD;
             weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline)&#xD;
             from adverse events due to a previously administered agent (exc. alopecia).&#xD;
&#xD;
          -  If subject received major surgery, they must have recovered adequately prior to&#xD;
             starting therapy.&#xD;
&#xD;
          -  Has a known additional malignancy that is progressing or requires active treatment.&#xD;
&#xD;
          -  Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the&#xD;
             skin, or in situ cervical cancer that has undergone potentially curative therapy.&#xD;
&#xD;
          -  Has known active central nervous system (CNS) metastases and/or carcinomatous&#xD;
             meningitis. Subjects with previously treated brain metastases may participate provided&#xD;
             they are stable (without evidence of progression by imaging for at least four weeks&#xD;
             prior to the first dose of trial treatment and any neurologic symptoms have returned&#xD;
             to baseline), have no evidence of new or enlarging brain metastases, and are not using&#xD;
             steroids for at least 7 days prior to trial treatment.&#xD;
&#xD;
          -  Has an active, known or suspected autoimmune disease requiring systemic treatment&#xD;
             within the past 3 months or a documented history of clinically severe autoimmune&#xD;
             disease, or a syndrome that requires systemic steroids or immunosuppressive agents.&#xD;
             Subjects with vitiligo or resolved childhood asthma/atopy, type 1 diabetes mellitus&#xD;
             are permitted. Subjects that require intermittent use of bronchodilators or local&#xD;
             steroid injections would not be excluded from the study. Subjects with hypothyroidism&#xD;
             stable on hormone replacement or Sjogren's syndrome will not be excluded from the&#xD;
             study.&#xD;
&#xD;
          -  Has an active infection requiring systemic therapy&#xD;
&#xD;
          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the trial, interfere with the subject's&#xD;
             participation for the full duration of the trial, or it is not in the best interest of&#xD;
             the subject to participate, in the opinion of the treating investigator.&#xD;
&#xD;
          -  Has known psychiatric or substance abuse disorders that would interfere with&#xD;
             cooperation with the requirements of the trial.&#xD;
&#xD;
          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the&#xD;
             projected duration of the trial, starting with the pre-screening or screening visit&#xD;
             through 5 months for females, 7 months for males after the last dose of trial&#xD;
             treatment.&#xD;
&#xD;
          -  Prior anti-PD-1, anti-PDL-1, anti-PDL-2, anti-Cytotoxic T-lymphocyte-associated&#xD;
             antigen-4 (CTLA-4) antibody or any other antibody or drug specifically targeting&#xD;
             T-cell co-stimulation or checkpoint pathways.&#xD;
&#xD;
          -  Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).&#xD;
&#xD;
          -  Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA&#xD;
             [qualitative] is detected).&#xD;
&#xD;
          -  Has received a live vaccine within 30 days prior to the first dose of trial treatment.&#xD;
&#xD;
          -  Subject is a prisoners, or compulsory detained&#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>Neil Segal, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)</name>
      <address>
        <city>Basking Ridge</city>
        <state>New Jersey</state>
        <zip>07920</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Monmouth (Limited Protocol Activities)</name>
      <address>
        <city>Middletown</city>
        <state>New Jersey</state>
        <zip>07748</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Bergen (Limited Protocol Activities)</name>
      <address>
        <city>Montvale</city>
        <state>New Jersey</state>
        <zip>07645</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Commack (Limited Protocol Activities)</name>
      <address>
        <city>Commack</city>
        <state>New York</state>
        <zip>11725</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Westchester (All Protocol Activities)</name>
      <address>
        <city>Harrison</city>
        <state>New York</state>
        <zip>10604</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center (All Protocol Activities)</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Nassau (Limited Protocol Activities)</name>
      <address>
        <city>Rockville Centre</city>
        <state>New York</state>
        <zip>11553</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mskcc.org/mskcc/html/44.cfm</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>June 26, 2020</study_first_submitted>
  <study_first_submitted_qc>June 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>March 8, 2023</last_update_submitted>
  <last_update_submitted_qc>March 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Temozolomide</keyword>
  <keyword>Cisplatin,</keyword>
  <keyword>Nivolumab</keyword>
  <keyword>20-202</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
    <mesh_term>Adenocarcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</mesh_term>
    <mesh_term>Temozolomide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.</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/NCT04457284
org study id: 20-202
nct id: NCT04457284
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
This study will test whether the combination of cisplatin, nivolumab, and temozolomide is an
      effective treatment for in people with advanced and/or metastatic colorectal cancer that is
      mismatch repair-proficient (MMR-proficient). The researchers will also look at how safe the
      study drug combination is in participants.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This will be a two-stage design, single arm, phase II study.
primary purpose: Treatment
masking: None (Open Label)
measure: Response
time frame: 1 year
description: will be evaluated in this study using the new international criteria proposed in RECIST 1.1 [Eur J Ca 45:228-247, 2009]. Changes in the largest diameter (unidimensional measurement) of the tumor and the shortest diameter of malignant lymph nodes are used with the RECIST criteria.
arm group label: temozolomide, cisplatin and nivolumab
arm group type: Experimental
description: Subjects will receive oral TMZ at 150-200 mg/m2 day 1 to 5 every 4 weeks, cisplatin via IV infusion at 40 mg/m2 every two weeks (Q2W), and nivolumab via IV infusion at 480 mg every four weeks (Q4W).
intervention type: Drug
intervention name: Temozolomide (TMZ)
description: TMZ 150 mg/m2 Day 1 - 5 Q4W PO Cycle 1
TMZ 200 mg/m2 Day 1 - 5 Q4W PO Cycle 2 +
arm group label: temozolomide, cisplatin and nivolumab
intervention type: Drug
intervention name: Cisplatin
description: Cisplatin 40 mg/m2 Q2W IV infusion Cycle 1 +
arm group label: temozolomide, cisplatin and nivolumab
intervention type: Drug
intervention name: Nivolumab
description: Nivolumab 480 mg Q4W IV infusion Cycle 1 +
arm group label: temozolomide, cisplatin and nivolumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Neil Segal, MD, PhD
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.mskcc.org/mskcc/html/44.cfm
description: Memorial Sloan Kettering Cancer Center
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Adenocarcinoma
mesh term: Nivolumab
mesh term: Temozolomide
sharing ipd: Yes
ipd description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.