<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/NCT03274804</url>
  </required_header>
  <id_info>
    <org_study_id>PICCASSO</org_study_id>
    <nct_id>NCT03274804</nct_id>
  </id_info>
  <brief_title>Combined PD-1 and CCR5 Inhibition for the Treatment of Refractory Microsatellite Stable mCRC</brief_title>
  <acronym>PICCASSO</acronym>
  <official_title>A Phase I Trial of Combined PD-1 Inhibition (Pembrolizumab) and CCR5 Inhibition (Maraviroc) for the Treatment of Refractory Microsatellite Stable (MSS) Metastatic Colorectal Cancer (mCRC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital Heidelberg</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital Heidelberg</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>
      This is a monocentric, single arm, prospective, open-label trial of a combination treatment&#xD;
      consisting of pembrolizumab and maraviroc in previously treated subjects who have refractory&#xD;
      microsatellite stable (MSS) metastatic colorectal cancer (mCRC).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Eligible subjects will receive pembrolizumab beginning on Day 1 of each 3-week dosing cycle&#xD;
      (d1, qd22) together with maraviroc administered perorally on day 1 to 21 of each cycle&#xD;
      (d1-21; qd22).&#xD;
&#xD;
      Treatment with pembrolizumab / maraviroc combination will continue until progressive disease&#xD;
      (PD), unacceptable adverse events (AEs), intercurrent illness that prevents further&#xD;
      administration of treatment, investigator's decision to withdraw the subject, subject&#xD;
      withdraws consent, pregnancy of the subject, noncompliance with trial treatment or procedure&#xD;
      requirements, administrative reasons requiring cessation of treatment, or completion of&#xD;
      treatment per protocol.&#xD;
&#xD;
      Subjects with a treatment response or stable disease after completion of the first treatment&#xD;
      phase of eight cycles (core treatment period) will be offered, at the discretion of the&#xD;
      investigator, participation in a maintenance phase consisting of up to 24 additional&#xD;
      treatment cycles of pembrolizumab monotherapy (total treatment duration up to 24 months).&#xD;
&#xD;
      Subjects who discontinue for reasons other than PD will have post-treatment follow-up for&#xD;
      disease status until PD, initiating a non-study cancer treatment, withdrawing consent, or&#xD;
      becoming lost to follow-up. All subjects will be followed for overall survival (OS) until&#xD;
      death, withdrawal of consent, loss to follow-up, or the end of the study.&#xD;
&#xD;
      After the end of treatment, each subject will be followed for 30 days for AE monitoring.&#xD;
      Serious adverse events (SAEs) and AEs of special interest (AESIs) will be collected for 90&#xD;
      days after the end of treatment or for 30 days after the end of treatment if the subject&#xD;
      initiates new anticancer therapy, whichever is earlier.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 1, 2018</start_date>
  <completion_date type="Actual">March 1, 2020</completion_date>
  <primary_completion_date type="Actual">March 1, 2020</primary_completion_date>
  <phase>Phase 1</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>Feasibility Rate of a Combined Therapy</measure>
    <time_frame>After core treatment period of 8 cycles (each cycle is 21 days)</time_frame>
    <description>Defined as the rate of patients receiving the protocol treatment according to the planned schedule without occurrence of at least one of the following events:&#xD;
Study treatment-related Grade ≥ 3 immune-related abnormalities; Study treatment-related Grade ≥ 4 AEs of any aetiology; Any toxic event leading to the premature withdrawal of protocol treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety and Toxicity of a Combined Therapy Based on Subjects Who Experienced Toxicities</measure>
    <time_frame>After core treatment period of 8 cycles (each cycle is 21 days)</time_frame>
    <description>The primary safety analysis will be based on subjects who experienced toxicities as defined by the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, v4.0; Section 11.2). The attribution to drug, time-of-onset, duration of the event, its resolution, and any concomitant medications administered will be recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy Endpoint: Disease Control Rate</measure>
    <time_frame>through study completion (20 months)</time_frame>
    <description>Determine DCR defined as percentage of patients displaying CR/PR or SD as best response according to the RECIST criteria version 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy Endpoint: Objective Response Rate</measure>
    <time_frame>through study completion (20 months)</time_frame>
    <description>ORR and immune related (ir) ORR (irORR) will be analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy Endpoint: Progression-free Survival</measure>
    <time_frame>through study completion (20 months)</time_frame>
    <description>Individual PFS will be analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>through study completion (20 months)</time_frame>
    <description>Individual OS will be analyzed.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Metastatic Colorectal Cancer</condition>
  <condition>MSS</condition>
  <arm_group>
    <arm_group_label>Single arm, prospective, open-label trial</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eligible subjects will receive pembrolizumab beginning on Day 1 of each 3-week dosing cycle (d1, qd22) together with maraviroc administered perorally on day 1 to 21 of each cycle (d1-21; qd22).</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Eligible subjects will receive pembrolizumab beginning on Day 1 of each 3-week dosing cycle (d1, qd22)</description>
    <arm_group_label>Single arm, prospective, open-label trial</arm_group_label>
    <other_name>Keytruda</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Maraviroc</intervention_name>
    <description>Maraviroc will be administered perorally on day 1 to 21 of each cycle (d1-21; qd22)</description>
    <arm_group_label>Single arm, prospective, open-label trial</arm_group_label>
    <other_name>Celsentri</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed metastatic colorectal cancer. Microsatellite stability (MSS)&#xD;
             is confirmed by PCR or immunohistochemistry.&#xD;
&#xD;
          2. Patient failed standard therapy or is intolerable towards standard therapy which must&#xD;
             include a fluoropyrimidine, oxaliplatin, irinotecan, an antiangiogenic monoclonal&#xD;
             antibody (e.g. bevacizumab, aflibercept, ramucirumab), an EGFR inhibitor in case of&#xD;
             RAS/BRAF wildtype tumors and optional regorafenib or TAS 102&#xD;
&#xD;
          3. Measurable disease as per RECIST 1.1&#xD;
&#xD;
          4. Metastatic lesion accessible for repetitive biopsies and patient willing to provide&#xD;
             tissue from newly obtained biopsies. Patients without accessible lesions might be&#xD;
             enrolled after discussion with the principle investigator.&#xD;
&#xD;
          5. ECOG performance status 0 or 1&#xD;
&#xD;
          6. Adequate hematological, hepatic and renal function parameters:&#xD;
&#xD;
               -  Leucocytes&gt; 3.000/μl&#xD;
&#xD;
               -  Hemoglobin &gt;9 g/dl&#xD;
&#xD;
               -  Thrombocytes &gt; 100.000/μl&#xD;
&#xD;
               -  Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or GFR ≥60 mL/min for&#xD;
                  subject with creatinine levels &gt; 1.5 x institutional ULN&#xD;
&#xD;
               -  Serum total bilirubin ≤ 1.5 x upper limit of normal or direct bilirubin ≤ ULN for&#xD;
                  subjects with total bilirubin levels &gt; 1.5 ULN&#xD;
&#xD;
               -  AST and ALT ≤ 2.5 x upper limit of normal (or ≤ 5 x if liver metastases are&#xD;
                  present)&#xD;
&#xD;
               -  Albumin ≥ 2.5 mg/dL&#xD;
&#xD;
          7. Adequate coagulation functions as defined by International Normalized Ratio (INR)&#xD;
             ≤1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless&#xD;
             receiving anticoagulation therapy). Patients receiving warfarin/ phenprocoumon must be&#xD;
             switched to low molecular weight heparin and have achieved stable coagulation profile.&#xD;
&#xD;
          8. Female and male patients' ≥ 18 years. Patients in reproductive age must be willing to&#xD;
             use adequate contraception during the study and 4 months after the end of the study&#xD;
             (appropriate contraception is defined as surgical sterilization (e.g., bilateral tubal&#xD;
             ligation, vasectomy), hormonal contraception (implantable, patch, oral), and&#xD;
             doublebarrier methods (any double combination of: IUD, male or female condom with&#xD;
             spermicidal gel, diaphragm, sponge, cervical cap)). Abstinence (relative to&#xD;
             heterosexual activity) can be used as the sole method of contraception if it is&#xD;
             consistently employed as the subject's preferred and usual lifestyle and if considered&#xD;
             acceptable by local regulatory agencies and ERCs/IRBs. Periodic abstinence (e.g.,&#xD;
             calendar, ovulation, sympto-thermal, post-ovulation methods, etc.) and withdrawal are&#xD;
             not acceptable methods of contraception. Female patients with childbearing potential&#xD;
             need to have a negative pregnancy test within 7 days before study start.&#xD;
&#xD;
          9. Patient able and willing to provide written informed consent and to comply with the&#xD;
             study protocol and with the planned surgical procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Inability to understand the aims of the study and/or protocol procedures&#xD;
&#xD;
          2. Hypersensitivity towards pembrolizumab, maraviroc, or any ingredients of the&#xD;
             formulations administered&#xD;
&#xD;
          3. History of severe allergic, anaphylactic, or other hypersensitivity reactions to&#xD;
             chimeric or humanized antibodies&#xD;
&#xD;
          4. Any other concurrent antineoplastic treatment including irradiation (local radiation&#xD;
             of single non-target lesions for palliation only allowed)&#xD;
&#xD;
          5. Active autoimmune disease requiring immunosuppressive therapy&#xD;
&#xD;
          6. Any condition requiring continuous systemic treatment with either corticosteroids (&gt;10&#xD;
             mg daily prednisone equivalents) or other immunosuppressive medications within 2 weeks&#xD;
             prior to first dose of study treatment. Inhaled or topical steroids and physiological&#xD;
             replacement doses of up to 10 mg daily prednisone equivalent are permitted in the&#xD;
             absence of active autoimmune disease.&#xD;
&#xD;
          7. Secondary malignant disease during the last 5 years (exceptions include basal cell&#xD;
             carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer&#xD;
             that has undergone potentially curative therapy).&#xD;
&#xD;
          8. Clinical relevant comorbidity also including significant psychiatric disease&#xD;
&#xD;
          9. Clinically significant active coronary heart disease, cardiomyopathy or congestive&#xD;
             heart failure, NYHA III-IV&#xD;
&#xD;
         10. Cardiocirculatory insufficiency with hypotension (systolic blood pressure &lt;100 mmHg)&#xD;
&#xD;
         11. Cirrhosis of the liver (Child &gt; Grade A), pronounced alcohol abuse with anticipated&#xD;
             detoxification, severe pulmonary infection with considerable reduction of pulmonary&#xD;
             function&#xD;
&#xD;
         12. Prior allogeneic bone marrow transplantation&#xD;
&#xD;
         13. Prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 therapeutic antibody&#xD;
&#xD;
         14. Administration of a live, attenuated vaccine within four weeks prior to start of&#xD;
             maintenance treatment or anticipation that such a live attenuated vaccine will be&#xD;
             required during the remainder of the study Note: Seasonal influenza vaccines for&#xD;
             injection are generally inactivated flu vaccines and are allowed; however intranasal&#xD;
             influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not&#xD;
             allowed.&#xD;
&#xD;
         15. Chronic intake of drugs that lead to known interference with Maraviroc metabolism&#xD;
             through strong Cytochrome P450 3A4 (CYP3A4) interaction: e.g. Rifampicin, Rifabutin,&#xD;
             Clarithromycin, Telithromycin, Ketoconazole, Itraconazole, Fluconazole, Hypericum&#xD;
             perforatum (St. John's Worth /Johanniskraut) or any strong CYP3A4 inducing or&#xD;
             inhibiting drug (See Section 5.5.2)&#xD;
&#xD;
         16. Positive test for human immunodeficiency virus (HIV) or HIV infection&#xD;
&#xD;
         17. Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg]&#xD;
             test) or hepatitis C. Note: Patients with past hepatitis B virus (HBV) infection or&#xD;
             resolved HBV infection (defined as having a negative HBsAg test and a positive&#xD;
             antibody to hepatitis B core antigen antibody test) are eligible.&#xD;
&#xD;
         18. Active or latent tuberculosis&#xD;
&#xD;
         19. Clinically active brain metastases, defined as untreated symptomatic, or requiring&#xD;
             therapy with steroids or anticonvulsants to control associated symptoms.&#xD;
&#xD;
             Subjects with treated brain metastases that are no longer symptomatic and require no&#xD;
             treatment with steroids may be included in the study if they have recovered from the&#xD;
             acute toxic effect of radiotherapy and have no evidence of disease progression on&#xD;
             imaging studies (MRI/CT scan).&#xD;
&#xD;
         20. On-treatment participation in another clinical study in the period 30 days prior to&#xD;
             start of study treatment and during the study&#xD;
&#xD;
         21. Patients in a closed institution according to an authority or court decision (AMG §&#xD;
             40, Abs. 1 No. 4)&#xD;
&#xD;
         22. Pregnancy or lactation&#xD;
&#xD;
         23. Known history of, or any evidence of active, non-infectious pneumonitis or&#xD;
             interstitial lung disease.&#xD;
&#xD;
         24. Active infection requiring systemic therapy.&#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>Dirk Jäger, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>NCT, Med Oncology, University Hospital Heidelberg</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Center for Tumor Diseases, University Hospital Heidelberg</name>
      <address>
        <city>Heidelberg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>August 14, 2017</study_first_submitted>
  <study_first_submitted_qc>September 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <results_first_submitted>February 1, 2021</results_first_submitted>
  <results_first_submitted_qc>March 23, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">April 22, 2021</results_first_posted>
  <last_update_submitted>May 17, 2022</last_update_submitted>
  <last_update_submitted_qc>May 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 7, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital Heidelberg</investigator_affiliation>
    <investigator_full_name>Dirk Jäger</investigator_full_name>
    <investigator_title>Prof. Dr.</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Maraviroc</mesh_term>
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 1, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/04/NCT03274804/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Single Arm, Prospective, Open-label Trial</title>
          <description>Eligible subjects will receive pembrolizumab beginning on Day 1 of each 3-week dosing cycle (d1, qd22) together with maraviroc administered perorally on day 1 to 21 of each cycle (d1-21; qd22).&#xD;
Pembrolizumab: Eligible subjects will receive pembrolizumab beginning on Day 1 of each 3-week dosing cycle (d1, qd22)&#xD;
Maraviroc: Maraviroc will be administered perorally on day 1 to 21 of each cycle (d1-21; qd22)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The required parameters as defined in the inclusion and exclusion criteria are met by all patients.</population>
      <group_list>
        <group group_id="B1">
          <title>Study Treatment Arm</title>
          <description>All enrolled subjects received pembrolizumab 200 mg IV on day one every three weeks (d1, qd22; Q3W) plus maraviroc 2 x 300 mg p.o. daily as combination therapy in an unblinded fashion.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="20"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61" spread="8.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Germany</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Feasibility Rate of a Combined Therapy</title>
        <description>Defined as the rate of patients receiving the protocol treatment according to the planned schedule without occurrence of at least one of the following events:&#xD;
Study treatment-related Grade ≥ 3 immune-related abnormalities; Study treatment-related Grade ≥ 4 AEs of any aetiology; Any toxic event leading to the premature withdrawal of protocol treatment</description>
        <time_frame>After core treatment period of 8 cycles (each cycle is 21 days)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single Arm, Prospective, Open-label Trial</title>
            <description>All enrolled subjects received pembrolizumab 200 mg IV on day one every three weeks (d1, qd22; Q3W) plus maraviroc 2 x 300 mg p.o. daily as combination therapy in an unblinded fashion.</description>
          </group>
        </group_list>
        <measure>
          <title>Feasibility Rate of a Combined Therapy</title>
          <description>Defined as the rate of patients receiving the protocol treatment according to the planned schedule without occurrence of at least one of the following events:&#xD;
Study treatment-related Grade ≥ 3 immune-related abnormalities; Study treatment-related Grade ≥ 4 AEs of any aetiology; Any toxic event leading to the premature withdrawal of protocol treatment</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Safety and Toxicity of a Combined Therapy Based on Subjects Who Experienced Toxicities</title>
        <description>The primary safety analysis will be based on subjects who experienced toxicities as defined by the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, v4.0; Section 11.2). The attribution to drug, time-of-onset, duration of the event, its resolution, and any concomitant medications administered will be recorded.</description>
        <time_frame>After core treatment period of 8 cycles (each cycle is 21 days)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Study Treatment Arm</title>
            <description>All enrolled subjects received pembrolizumab 200 mg IV on day one every three weeks (d1, qd22; Q3W) plus maraviroc 2 x 300 mg p.o. daily as combination therapy in an unblinded fashion.</description>
          </group>
        </group_list>
        <measure>
          <title>Safety and Toxicity of a Combined Therapy Based on Subjects Who Experienced Toxicities</title>
          <description>The primary safety analysis will be based on subjects who experienced toxicities as defined by the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, v4.0; Section 11.2). The attribution to drug, time-of-onset, duration of the event, its resolution, and any concomitant medications administered will be recorded.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Efficacy Endpoint: Disease Control Rate</title>
        <description>Determine DCR defined as percentage of patients displaying CR/PR or SD as best response according to the RECIST criteria version 1.1.</description>
        <time_frame>through study completion (20 months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Study Treatment Arm</title>
            <description>All enrolled subjects received pembrolizumab 200 mg IV on day one every three weeks (d1, qd22; Q3W) plus maraviroc 2 x 300 mg p.o. daily as combination therapy in an unblinded fashion.</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy Endpoint: Disease Control Rate</title>
          <description>Determine DCR defined as percentage of patients displaying CR/PR or SD as best response according to the RECIST criteria version 1.1.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Efficacy Endpoint: Objective Response Rate</title>
        <description>ORR and immune related (ir) ORR (irORR) will be analyzed.</description>
        <time_frame>through study completion (20 months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Single Arm, Prospective, Open-label Trial</title>
            <description>All enrolled subjects received pembrolizumab 200 mg IV on day one every three weeks (d1, qd22; Q3W) plus maraviroc 2 x 300 mg p.o. daily as combination therapy in an unblinded fashion.</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy Endpoint: Objective Response Rate</title>
          <description>ORR and immune related (ir) ORR (irORR) will be analyzed.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Efficacy Endpoint: Progression-free Survival</title>
        <description>Individual PFS will be analyzed.</description>
        <time_frame>through study completion (20 months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Study Treatment Arm</title>
            <description>All enrolled subjects received pembrolizumab 200 mg IV on day one every three weeks (d1, qd22; Q3W) plus maraviroc 2 x 300 mg p.o. daily as combination therapy in an unblinded fashion.</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy Endpoint: Progression-free Survival</title>
          <description>Individual PFS will be analyzed.</description>
          <units>weeks</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9" lower_limit="7.00" upper_limit="10.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>Individual OS will be analyzed.</description>
        <time_frame>through study completion (20 months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Study Treatment Arm</title>
            <description>All enrolled subjects received pembrolizumab 200 mg IV on day one every three weeks (d1, qd22; Q3W) plus maraviroc 2 x 300 mg p.o. daily as combination therapy in an unblinded fashion.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Individual OS will be analyzed.</description>
          <units>Time until event, month</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9" lower_limit="6.00" upper_limit="20.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the time of treatment allocation through 30 days following discontinuation of treatment, up to 20 months, all adverse events must be reported by the investigator.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Study Treatment Arm</title>
          <description>The primary safety analysis will be based on subjects who experienced toxicities as defined by the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, v4.0; Section 11.2). The attribution to drug, time-of-onset, duration of the event, its resolution, and any concomitant medications administered will be recorded.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations - Other</sub_title>
                <description>unknown origin</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Catheter related infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Blood and lymphatic system disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear and labyrinth disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Eye disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Keratitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Anal hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hemorrhoidal hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Rectal hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Stomach pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Localized edema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Gallbladder obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchial infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Catheter related infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Infections and infestations - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Nail infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Rash pustular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Salivary gland infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Investigations - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Weight gain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Metabolism and nutrition disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Chest wall pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorder - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Tumor pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal and urinary disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Urinary frequency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Reproductive system and breast disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Georg Martin Haag</name_or_title>
      <organization>Universitätsklinikum Heidelberg, NCT</organization>
      <phone>+49 (0) 6221 56 ext 4801</phone>
      <email>GeorgMartin.Haag@med.uni-heidelberg.de</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03274804
org study id: PICCASSO
nct id: NCT03274804
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a monocentric, single arm, prospective, open-label trial of a combination treatment
      consisting of pembrolizumab and maraviroc in previously treated subjects who have refractory
      microsatellite stable (MSS) metastatic colorectal cancer (mCRC).
Eligible subjects will receive pembrolizumab beginning on Day 1 of each 3-week dosing cycle
      (d1, qd22) together with maraviroc administered perorally on day 1 to 21 of each cycle
      (d1-21; qd22).

      Treatment with pembrolizumab / maraviroc combination will continue until progressive disease
      (PD), unacceptable adverse events (AEs), intercurrent illness that prevents further
      administration of treatment, investigator's decision to withdraw the subject, subject
      withdraws consent, pregnancy of the subject, noncompliance with trial treatment or procedure
      requirements, administrative reasons requiring cessation of treatment, or completion of
      treatment per protocol.

      Subjects with a treatment response or stable disease after completion of the first treatment
      phase of eight cycles (core treatment period) will be offered, at the discretion of the
      investigator, participation in a maintenance phase consisting of up to 24 additional
      treatment cycles of pembrolizumab monotherapy (total treatment duration up to 24 months).

      Subjects who discontinue for reasons other than PD will have post-treatment follow-up for
      disease status until PD, initiating a non-study cancer treatment, withdrawing consent, or
      becoming lost to follow-up. All subjects will be followed for overall survival (OS) until
      death, withdrawal of consent, loss to follow-up, or the end of the study.

      After the end of treatment, each subject will be followed for 30 days for AE monitoring.
      Serious adverse events (SAEs) and AEs of special interest (AESIs) will be collected for 90
      days after the end of treatment or for 30 days after the end of treatment if the subject
      initiates new anticancer therapy, whichever is earlier.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Feasibility Rate of a Combined Therapy
time frame: After core treatment period of 8 cycles (each cycle is 21 days)
description: Defined as the rate of patients receiving the protocol treatment according to the planned schedule without occurrence of at least one of the following events:
Study treatment-related Grade ≥ 3 immune-related abnormalities; Study treatment-related Grade ≥ 4 AEs of any aetiology; Any toxic event leading to the premature withdrawal of protocol treatment
measure: Safety and Toxicity of a Combined Therapy Based on Subjects Who Experienced Toxicities
time frame: After core treatment period of 8 cycles (each cycle is 21 days)
description: The primary safety analysis will be based on subjects who experienced toxicities as defined by the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, v4.0; Section 11.2). The attribution to drug, time-of-onset, duration of the event, its resolution, and any concomitant medications administered will be recorded.
measure: Efficacy Endpoint: Disease Control Rate
time frame: through study completion (20 months)
description: Determine DCR defined as percentage of patients displaying CR/PR or SD as best response according to the RECIST criteria version 1.1.
measure: Efficacy Endpoint: Objective Response Rate
time frame: through study completion (20 months)
description: ORR and immune related (ir) ORR (irORR) will be analyzed.
measure: Efficacy Endpoint: Progression-free Survival
time frame: through study completion (20 months)
description: Individual PFS will be analyzed.
measure: Overall Survival
time frame: through study completion (20 months)
description: Individual OS will be analyzed.
arm group label: Single arm, prospective, open-label trial
arm group type: Experimental
description: Eligible subjects will receive pembrolizumab beginning on Day 1 of each 3-week dosing cycle (d1, qd22) together with maraviroc administered perorally on day 1 to 21 of each cycle (d1-21; qd22).
intervention type: Biological
intervention name: Pembrolizumab
description: Eligible subjects will receive pembrolizumab beginning on Day 1 of each 3-week dosing cycle (d1, qd22)
arm group label: Single arm, prospective, open-label trial
other name: Keytruda
intervention type: Drug
intervention name: Maraviroc
description: Maraviroc will be administered perorally on day 1 to 21 of each cycle (d1-21; qd22)
arm group label: Single arm, prospective, open-label trial
other name: Celsentri
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dirk Jäger, Prof.
role: Principal Investigator
affiliation: NCT, Med Oncology, University Hospital Heidelberg
facility: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: University Hospital Heidelberg
investigator full name: Dirk Jäger
investigator title: Prof. Dr.
mesh term: Colorectal Neoplasms
mesh term: Maraviroc
mesh term: Pembrolizumab
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 