<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/NCT03791398</url>
  </required_header>
  <id_info>
    <org_study_id>BrUOG 379</org_study_id>
    <nct_id>NCT03791398</nct_id>
  </id_info>
  <brief_title>BrUOG 379 Phase Ib/II Trial ONC201 + Nivolumab in MSS mCRC</brief_title>
  <acronym>379</acronym>
  <official_title>BrUOG 379: A Phase Ib/II Single Arm Study of ONC201 Plus Nivolumab in Microsatellite Stable (MSS) Metastatic Colorectal Cancer (mCRC) Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brown University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Rhode Island Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Oncoceutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Brown University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single arm Phase Ib/II, open label, safety, pharmacokinetic, pharmacodynamics and&#xD;
      efficacy study of ONC201 in combination with Opdivo (Nivolumab) in adult patients with&#xD;
      metastatic colorectal cancer, for whom no standard therapy is available. This study will&#xD;
      enroll adult patients with metastatic colorectal cancer who progressed after at least two&#xD;
      lines of therapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Lack of efficacy&#xD;
  </why_stopped>
  <start_date type="Actual">November 15, 2019</start_date>
  <completion_date type="Actual">August 5, 2021</completion_date>
  <primary_completion_date type="Actual">June 16, 2021</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>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>This is a single arm study of de-escalating arms to determine the MTD and then expand the trial.It is not randomized.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Tolerated Dose of ONC201 With Nivolumab for Phase II</measure>
    <time_frame>Cycle 1 (each cycle is approximately 4 weeks) through pre-dosing cycle 2, approximately 1 month</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>From start of protocol therapy until death or progression, a maximum of 6 months from end of therapy.</time_frame>
    <description>Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Metastatic Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>ONC201 Level 1 (Starting Dose Level)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>625mg ONC201 Cycle 1 Day -7 dose then once week</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ONC201 Level 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>500 mg ONC201 Cycle 1 Day -7 dose then once week</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ONC201 Level 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>375 mg ONC201 Cycle 1 Day -7 dose then once week</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Nivolumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>240mg IV flat dose q 2 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dose level 1 ONC201 625mg</intervention_name>
    <description>ONC201 625mg + Nivolumab 240mg IV flat dose</description>
    <arm_group_label>Nivolumab</arm_group_label>
    <arm_group_label>ONC201 Level 1 (Starting Dose Level)</arm_group_label>
    <other_name>ONC201 + Nivolumab</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dose level 2 ONC201 500mg</intervention_name>
    <description>ONC201 500mg + Nivolumab 240mg IV flat dose</description>
    <arm_group_label>Nivolumab</arm_group_label>
    <arm_group_label>ONC201 Level 2</arm_group_label>
    <other_name>ONC201 + Nivolumab</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dose level 3 ONC201 375mg</intervention_name>
    <description>ONC201 375mg + Nivolumab 240mg IV flat dose</description>
    <arm_group_label>Nivolumab</arm_group_label>
    <arm_group_label>ONC201 Level 3</arm_group_label>
    <other_name>ONC201 + Nivolumab</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients must have a histologically/cytologically -confirmed primary colorectal tumor,&#xD;
             with confirmation of being microsatellite stable.&#xD;
&#xD;
          2. Radiographic or clinical evidence of metastatic disease that has progressed after at&#xD;
             least 2 prior regimens. Prior bevacizumab, cetuximab, trifluridine and tipiracil , or&#xD;
             regorafenib is allowed, prior FOLFIRI and FOLFOX treatment is required. (Treatment&#xD;
             with a FOLFIRINOX regimen will count as 2 regimens). Prior treatment does not have to&#xD;
             have been in the metastatic setting.&#xD;
&#xD;
          3. Patients must have measurable disease by RECIST criteria&#xD;
&#xD;
          4. All patients must have a tumor(s) located in an area that that can be biopsied as&#xD;
             confirmed by treating physician&#xD;
&#xD;
          5. All patients must submit representative tissue from their malignancy if it is&#xD;
             confirmed there is enough tissue from prior surgery or most recent biopsy.&#xD;
&#xD;
          6. All previous therapies for cancer, including radiotherapy, major surgery and&#xD;
             investigational therapies must be discontinued for ≥ 14 days before the first dose of&#xD;
             ONC201&#xD;
&#xD;
          7. All clinically significant adverse events related to any prior therapy must have&#xD;
             resolved to Grade ≤ 1 Common Terminology Criteria for Adverse Events (CTCAE v5.0),&#xD;
             except alopecia or parameters defined in this eligibility list.&#xD;
&#xD;
          8. Age ≥ 18 years.&#xD;
&#xD;
          9. ECOG performance status ≤ 2.&#xD;
&#xD;
         10. Adequate organ and marrow function as defined below:&#xD;
&#xD;
               1. Absolute neutrophil count ≥1,000/mm3 without growth factor use ≤ 7 days prior to&#xD;
                  treatment&#xD;
&#xD;
               2. Platelets ≥75,000/mm3 without platelet transfusion ≤ 7 days prior to treatment&#xD;
&#xD;
               3. Hemoglobin&gt;8.0 mg/dL without red blood cell transfusion ≤ 7 days prior to&#xD;
                  treatment&#xD;
&#xD;
               4. Total serum bilirubin&lt;1.5 X upper limit of normal (ULN)&#xD;
&#xD;
               5. AST (SGOT)/ALT (SGPT)≤2 X ULN; ≤ 5 X ULN if liver dysfunction is felt to be&#xD;
                  secondary to tumor burden within 14 days prior to treatment, Serum creatinine ≤&#xD;
                  1.5 X ULN (OR creatinine clearance ≥ 60 mL/min/1.73 m2) within 14 days prior to&#xD;
                  treatment&#xD;
&#xD;
               6. Serum or urine pregnancy test (for females of childbearing potential) negative ≤7&#xD;
                  days of treatment&#xD;
&#xD;
         11. Ability to understand and the willingness to sign a written informed consent document&#xD;
             and comply with the study scheduled visits, treatment plans, laboratory tests and&#xD;
             other procedures.&#xD;
&#xD;
         12. Female patients of child-bearing potential must be practicing an effective form of&#xD;
             contraception from the time of informed consent and for the duration of the study&#xD;
             treatment through 5 months after the last dose of drug (ONC201 or Nivolumab, whichever&#xD;
             is administered last). The decision of effective contraception will be based on the&#xD;
             judgment of the principal investigator or a designated associate.&#xD;
&#xD;
         13. Male patients must be surgically sterile (provide date of surgery) or must agree to&#xD;
             use effective contraception from the time of informed consent and for the duration of&#xD;
             the study treatment through 7 months after the last dose of drug (ONC201 or Nivolumab,&#xD;
             whichever is administered last). The decision of effective contraception will be based&#xD;
             on the judgment of the principal investigator or a designated associate.&#xD;
&#xD;
         14. Patients must agree to the required tumor biopsies to enroll in the trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with symptomatic brain metastases are excluded. Patients with asymptomatic&#xD;
             and treated CNS metastases may participate in this trial. The patient must have&#xD;
             completed any prior treatment for CNS metastases &gt; 28 days prior to registration,&#xD;
             including radiotherapy or surgery. Steroids for the treatment of brain metastasis are&#xD;
             not permitted.&#xD;
&#xD;
          2. Patients with prior treatment with ONC201 will be excluded&#xD;
&#xD;
          3. Active inflammatory gastrointestinal disease such as severe chronic diarrhea (unless&#xD;
             related to underlying malignancy), gastrointestinal perforation, or intra-abdominal&#xD;
             abscess within 6 months prior to study registration. Gastroesophageal reflux disease&#xD;
             under controlled treatment with proton pump inhibitors is allowed.&#xD;
&#xD;
          4. Pregnant or breast feeding.&#xD;
&#xD;
          5. Current active treatment in another clinical study (treatment trial) within 14 days of&#xD;
             D-7.&#xD;
&#xD;
          6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection requiring IV antibiotics, hepatitis, active rheumatologic or collagen&#xD;
             vascular disease, symptomatic congestive heart failure, unstable angina pectoris,&#xD;
             clinically significant cardiac arrhythmia, or psychiatric illness/social situations&#xD;
             that would limit compliance with study requirements.&#xD;
&#xD;
          7. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome&#xD;
             (AIDS)-related illness. (testing is not required for eligibility).&#xD;
&#xD;
          8. Any of the following in the previous 3 months: myocardial infarction, severe/unstable&#xD;
             angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure,&#xD;
             cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism&#xD;
             as defined by treating physician.&#xD;
&#xD;
          9. Other severe acute or chronic medical or psychiatric condition or laboratory&#xD;
             abnormality that may increase the risk associated with study participation or study&#xD;
             drug administration, or may interfere with the interpretation of study results, or in&#xD;
             the judgment of the investigator would make the patient inappropriate for entry into&#xD;
             the study.&#xD;
&#xD;
         10. Participants with an active, known or suspected autoimmune disease. Participants with&#xD;
             type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin&#xD;
             disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment,&#xD;
             or conditions not expected to recur in the absence of an external trigger are&#xD;
             permitted to enroll.&#xD;
&#xD;
         11. Participants with a condition requiring systemic treatment with either corticosteroids&#xD;
             (&gt; 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14&#xD;
             days of day 1 of treatment. Inhaled or topical steroids, and adrenal replacement&#xD;
             steroid doses &gt; 10 mg daily prednisone equivalent, are permitted in the absence of&#xD;
             active autoimmune disease&#xD;
&#xD;
         12. Patients with a history of other invasive malignancies, with the exception of&#xD;
             non-melanoma skin cancer are excluded if there is any evidence of other malignancy&#xD;
             being present within the last three years (2 years for invasive breast cancer).&#xD;
             However, patients with a malignancy that is non-likely to require treatment, as per&#xD;
             the treating physician, in the next 2 years, such as a completely resected, early&#xD;
             stage breast cancer, or other malignancies treated with curative intent are eligible.&#xD;
             Patients are also excluded if their previous cancer treatment contraindicates this&#xD;
             protocol therapy.&#xD;
&#xD;
         13. Prior treatment with immunotherapy for any cancer, including immune checkpoint&#xD;
             inhibitors or anti-CTLA4 agents&#xD;
&#xD;
         14. Participants who have received a live / attenuated vaccine within 30 days of first&#xD;
             treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Lifespan Cancer Institute: The Miriam and Rhode Island Hospitals</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>December 26, 2018</study_first_submitted>
  <study_first_submitted_qc>December 31, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">January 2, 2019</study_first_posted>
  <results_first_submitted>April 28, 2022</results_first_submitted>
  <results_first_submitted_qc>May 25, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">June 21, 2022</results_first_posted>
  <last_update_submitted>February 15, 2023</last_update_submitted>
  <last_update_submitted_qc>February 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Metastatic</keyword>
  <keyword>colorectal cancer</keyword>
  <keyword>colon cancer</keyword>
  <keyword>microsatellite stable</keyword>
  <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>Nivolumab</mesh_term>
    <mesh_term>TIC10 compound</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 30, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/98/NCT03791398/Prot_SAP_ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>ONC201 Level 1 (Starting Dose Level)</title>
          <description>625mg ONC201 Cycle 1 Day -7 dose then once week&#xD;
Dose level 1 ONC201 625mg: ONC201 625mg + Nivolumab 240mg IV flat dose</description>
        </group>
        <group group_id="P2">
          <title>ONC201 Level 2</title>
          <description>500 mg ONC201 Cycle 1 Day -7 dose then once week&#xD;
Dose level 2 ONC201 500mg: ONC201 500mg + Nivolumab 240mg IV flat dose</description>
        </group>
        <group group_id="P3">
          <title>ONC201 Level 3</title>
          <description>375 mg ONC201 Cycle 1 Day -7 dose then once week&#xD;
Dose level 3 ONC201 375mg: ONC201 375mg + Nivolumab 240mg IV flat dose</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Progression of Disease Under Study</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>No patients were enrolled to dose level 2 or 3.</population>
      <group_list>
        <group group_id="B1">
          <title>ONC201 Level 1 (Starting Dose Level)</title>
          <description>625mg ONC201 Cycle 1 Day -7 dose then once week&#xD;
Dose level 1 ONC201 625mg: ONC201 625mg + Nivolumab 240mg IV flat dose</description>
        </group>
        <group group_id="B2">
          <title>ONC201 Level 2</title>
          <description>500 mg ONC201 Cycle 1 Day -7 dose then once week&#xD;
Dose level 2 ONC201 500mg: ONC201 500mg + Nivolumab 240mg IV flat dose</description>
        </group>
        <group group_id="B3">
          <title>ONC201 Level 3</title>
          <description>375 mg ONC201 Cycle 1 Day -7 dose then once week&#xD;
Dose level 3 ONC201 375mg: ONC201 375mg + Nivolumab 240mg IV flat dose</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="13"/>
            <count group_id="B2" value="0"/>
            <count group_id="B3" value="0"/>
            <count group_id="B4" value="13"/>
          </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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="60" lower_limit="34" upper_limit="84"/>
                    <measurement group_id="B4" value="60" lower_limit="34" upper_limit="84"/>
                  </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="8"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B4" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B4" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Maximum Tolerated Dose of ONC201 With Nivolumab for Phase II</title>
        <time_frame>Cycle 1 (each cycle is approximately 4 weeks) through pre-dosing cycle 2, approximately 1 month</time_frame>
        <group_list>
          <group group_id="O1">
            <title>ONC201 Level 1 (Starting Dose Level)</title>
            <description>625mg ONC201 Cycle 1 Day -7 dose then once week&#xD;
Dose level 1 ONC201 625mg: ONC201 625mg + Nivolumab 240mg IV flat dose</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Tolerated Dose of ONC201 With Nivolumab for Phase II</title>
          <units>mg</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="625"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Progression Free Survival</title>
        <description>Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
        <time_frame>From start of protocol therapy until death or progression, a maximum of 6 months from end of therapy.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>ONC201 Level 1 (Starting Dose Level)</title>
            <description>625mg ONC201 Cycle 1 Day -7 dose then once week&#xD;
Dose level 1 ONC201 625mg: ONC201 625mg + Nivolumab 240mg IV flat dose</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival</title>
          <description>Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58" lower_limit="9" upper_limit="97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>All adverse events were collected from the time a signed and dated ICF is obtained until 100 days (+1 week) after the last treatment (Nivolumab or ONC201, whichever is last), or until the subject withdraws consent from study participation or at the time patient becomes a screen failure, whichever occurs first. An average of 6 months.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>ONC201 Level 1 (Starting Dose Level)</title>
          <description>625mg ONC201 Cycle 1 Day -7 dose then once week&#xD;
Dose level 1 ONC201 625mg: ONC201 625mg + Nivolumab 240mg IV flat dose</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (5.0)</default_vocab>
        <default_assessment>Non-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="11" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Disease progression</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Biliary obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Fungemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Abdominal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </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="13"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle weakness right-sided</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Endoscopic retrograde cholangiopancreatography</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (5.0)</default_vocab>
        <default_assessment>Non-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="13" subjects_at_risk="13"/>
              </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="2" subjects_at_risk="13"/>
              </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="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Abdominal cramping</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Thyroid stimulating hormone increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </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="13"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>Brown University Oncology Research Group</name_or_title>
      <organization>BrUOG</organization>
      <phone>401-863-3000</phone>
      <email>BrUOG@Brown.edu</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/NCT03791398
org study id: BrUOG 379
nct id: NCT03791398
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is a single arm Phase Ib/II, open label, safety, pharmacokinetic, pharmacodynamics and
      efficacy study of ONC201 in combination with Opdivo (Nivolumab) in adult patients with
      metastatic colorectal cancer, for whom no standard therapy is available. This study will
      enroll adult patients with metastatic colorectal cancer who progressed after at least two
      lines of therapy.
allocation: Non-Randomized
intervention model: Single Group Assignment
intervention model description: This is a single arm study of de-escalating arms to determine the MTD and then expand the trial.It is not randomized.
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose of ONC201 With Nivolumab for Phase II
time frame: Cycle 1 (each cycle is approximately 4 weeks) through pre-dosing cycle 2, approximately 1 month
measure: Progression Free Survival
time frame: From start of protocol therapy until death or progression, a maximum of 6 months from end of therapy.
description: Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
arm group label: ONC201 Level 1 (Starting Dose Level)
arm group type: Experimental
description: 625mg ONC201 Cycle 1 Day -7 dose then once week
arm group label: ONC201 Level 2
arm group type: Experimental
description: 500 mg ONC201 Cycle 1 Day -7 dose then once week
arm group label: ONC201 Level 3
arm group type: Experimental
description: 375 mg ONC201 Cycle 1 Day -7 dose then once week
arm group label: Nivolumab
arm group type: Experimental
description: 240mg IV flat dose q 2 weeks
intervention type: Drug
intervention name: Dose level 1 ONC201 625mg
description: ONC201 625mg + Nivolumab 240mg IV flat dose
arm group label: Nivolumab
arm group label: ONC201 Level 1 (Starting Dose Level)
other name: ONC201 + Nivolumab
intervention type: Drug
intervention name: Dose level 2 ONC201 500mg
description: ONC201 500mg + Nivolumab 240mg IV flat dose
arm group label: Nivolumab
arm group label: ONC201 Level 2
other name: ONC201 + Nivolumab
intervention type: Drug
intervention name: Dose level 3 ONC201 375mg
description: ONC201 375mg + Nivolumab 240mg IV flat dose
arm group label: Nivolumab
arm group label: ONC201 Level 3
other name: ONC201 + Nivolumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Nivolumab
mesh term: TIC10 compound
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 