<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/NCT04439201</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2020-03171</org_study_id>
    <secondary_id>NCI-2020-03171</secondary_id>
    <secondary_id>EAY131-Z1B</secondary_id>
    <secondary_id>EAY131-Z1B</secondary_id>
    <secondary_id>U10CA180820</secondary_id>
    <secondary_id>U24CA196172</secondary_id>
    <nct_id>NCT04439201</nct_id>
  </id_info>
  <brief_title>Testing Palbociclib (PD-0332991) as a Potential Targeted Treatment in Cancers With CCND1, 2, 3 Amplification (MATCH-Subprotocol Z1B)</brief_title>
  <official_title>MATCH Treatment Subprotocol Z1B: Phase II Study of Palbociclib (PD-0332991) in Patients With Tumors With CCND1, 2, 3 Amplification</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cancer Institute (NCI)</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II MATCH treatment trial identifies the effects of palbociclib in patients whose&#xD;
      cancer has genetic changes called CCND1, 2, or 3 amplification. Palbociclib blocks proteins&#xD;
      called CDK4 and CDK6, which may stop cancer cell growth when CCND1, 2, or 3 amplifications&#xD;
      are present. Researchers hope to learn if palbociclib will shrink this type of cancer or stop&#xD;
      its growth.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To evaluate the proportion of patients with objective response (OR) to targeted study&#xD;
      agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the proportion of patients alive and progression free at 6 months of treatment&#xD;
      with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple&#xD;
      myeloma.&#xD;
&#xD;
      II. To evaluate time until death or disease progression. III. To identify potential&#xD;
      predictive biomarkers beyond the genomic alteration by which treatment is assigned or&#xD;
      resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and&#xD;
      imaging-based assessment platforms.&#xD;
&#xD;
      IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes&#xD;
      from pre- through post-therapy imaging can predict objective response and progression free&#xD;
      survival and to evaluate the association between pre-treatment radiomic phenotypes and&#xD;
      targeted gene mutation patterns of tumor biopsy specimens.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive palbociclib orally (PO) once daily (QD) on days 1-21. Cycles repeat every 28&#xD;
      days in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 months if less than 2&#xD;
      years from study entry, and then every 6 months for year 3 from study entry.&#xD;
&#xD;
      THE MATCH SCREENING TRIAL:&#xD;
&#xD;
      Please see NCT02465060 for information on the MATCH Screening Protocol and applicable&#xD;
      documents.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 9, 2016</start_date>
  <completion_date type="Anticipated">December 31, 2025</completion_date>
  <primary_completion_date type="Actual">March 9, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration</time_frame>
    <description>ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable patients. Objective response is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Details about how to define complete response and partial response can be found in the master protocol. 90% two-sided binomial exact confidence interval is calculated for ORR.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>6-month Progression-free Survival (PFS) Rate</measure>
    <time_frame>Assessed at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration, from which 6-month PFS rate is determined</time_frame>
    <description>Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration</time_frame>
    <description>PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Advanced Lymphoma</condition>
  <condition>Advanced Malignant Solid Neoplasm</condition>
  <condition>Hematopoietic and Lymphoid Cell Neoplasm</condition>
  <condition>Refractory Lymphoma</condition>
  <condition>Refractory Malignant Solid Neoplasm</condition>
  <arm_group>
    <arm_group_label>Treatment (palbociclib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive palbociclib 125 mg PO QD days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Palbociclib</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (palbociclib)</arm_group_label>
    <other_name>6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one</other_name>
    <other_name>Ibrance</other_name>
    <other_name>PD 0332991</other_name>
    <other_name>PD 332991</other_name>
    <other_name>PD 991</other_name>
    <other_name>PD-0332991</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have met applicable eligibility criteria in the Master MATCH Protocol&#xD;
             prior to registration to treatment subprotocol&#xD;
&#xD;
          -  Patients must have amplification of CCND1, 2, or 3, or another aberration, as&#xD;
             determined via the MATCH Master Protocol&#xD;
&#xD;
          -  Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment&#xD;
             assignment and must have no clinically important abnormalities in rhythm, conduction&#xD;
             or morphology of resting ECG (e.g. complete left bundle branch block, third degree&#xD;
             heart block)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients must not have known hypersensitivity to palbociclib or compounds of similar&#xD;
             chemical or biologic composition&#xD;
&#xD;
          -  Patients must not have breast cancer, mantle cell lymphoma or myeloma&#xD;
&#xD;
          -  Patients with known or symptoms of left ventricular dysfunction will be excluded&#xD;
&#xD;
          -  Patients must not have had prior treatment with palbociclib, ribociclib, abemaciclib&#xD;
             or any other CDK4/6 inhibitors&#xD;
&#xD;
          -  Patients must not be using drugs or foods that are known potent CYP3A4 inhibitors or&#xD;
             inducers, or are CYP3A4 substrates with narrow therapeutic indices&#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>Amy S Clark</last_name>
    <role>Principal Investigator</role>
    <affiliation>ECOG-ACRIN Cancer Research Group</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ECOG-ACRIN Cancer Research Group</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Clark AS, Hong F, Finn RS, DeMichele AM, Mitchell EP, Zwiebel J, Arnaldez FI, Gray RJ, Wang V, McShane LM, Rubinstein LV, Patton D, Williams PM, Hamilton SR, Copur MS, Kasbari SS, Thind R, Conley BA, Arteaga CL, O'Dwyer PJ, Harris LN, Chen AP, Flaherty KT. Phase II Study of Palbociclib (PD-0332991) in CCND1, 2, or 3 Amplification: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1B. Clin Cancer Res. 2023 Apr 14;29(8):1477-1483. doi: 10.1158/1078-0432.CCR-22-2150.</citation>
    <PMID>36853016</PMID>
  </results_reference>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>June 18, 2020</study_first_submitted>
  <study_first_submitted_qc>June 18, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 19, 2020</study_first_posted>
  <results_first_submitted>July 28, 2023</results_first_submitted>
  <results_first_submitted_qc>July 28, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">August 24, 2023</results_first_posted>
  <last_update_submitted>July 28, 2023</last_update_submitted>
  <last_update_submitted_qc>July 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>NCI-MATCH</keyword>
  <keyword>Palbociclib</keyword>
  <keyword>CCND</keyword>
  <keyword>Retinoblastoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Palbociclib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 21, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/01/NCT04439201/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Subprotocol Z1B was activated on May 31, 2016. Forty patients were enrolled between August 2016 and December 2017.</recruitment_details>
      <pre_assignment_details>To be eligible for this subprotocol, tumors had to contain both an amplification in CCND1, 2, or 3 and Rb expression. CCND amplification was defined as seven or more copies of the gene; Rb expression was defined as 1+ or greater staining by IHC. The mutation status was determined by a CLIA-approved assay performed in a NCI-MATCH approved laboratory for all patients in this arm. Confirmatory central testing was required in order for these patients to be included in the primary analysis.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Treatment (Palbociclib)</title>
          <description>Patients receive palbociclib 125 mg PO QD days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity&#xD;
Palbociclib: Given PO</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Eligible</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Started Protocol Therapy</title>
              <participants_list>
                <participants group_id="P1" count="38"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Eligible and Treated</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Mutation Status Confirmed</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Eligible, Treated and Mutation Status Confirmed</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Ineligible</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Never start protocol therapy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Ineligible and never start protocol therapy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Mutation status not confirmed</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Disease progression</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Alternative therapy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Patients who were eligible, started protocol therapy, and had mutation status confirmed at the analysis time were the analyzable patients</population>
      <group_list>
        <group group_id="B1">
          <title>Treatment (Palbociclib)</title>
          <description>Patients receive palbociclib 125 mg PO QD days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity&#xD;
Palbociclib: Given PO</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="32"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62" lower_limit="38" upper_limit="78"/>
                  </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="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                  </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_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                  </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="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Objective Response Rate (ORR)</title>
        <description>ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable patients. Objective response is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Details about how to define complete response and partial response can be found in the master protocol. 90% two-sided binomial exact confidence interval is calculated for ORR.</description>
        <time_frame>Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration</time_frame>
        <population>Eligible, treated and mutation status confirmed</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Palbociclib)</title>
            <description>Patients receive palbociclib 125 mg PO QD days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity&#xD;
Palbociclib: Given PO</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR)</title>
          <description>ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable patients. Objective response is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Details about how to define complete response and partial response can be found in the master protocol. 90% two-sided binomial exact confidence interval is calculated for ORR.</description>
          <population>Eligible, treated and mutation status confirmed</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>6-month Progression-free Survival (PFS) Rate</title>
        <description>Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.</description>
        <time_frame>Assessed at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration, from which 6-month PFS rate is determined</time_frame>
        <population>Eligible, treated and mutation status confirmed</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Palbociclib)</title>
            <description>Patients receive palbociclib 125 mg PO QD days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity&#xD;
Palbociclib: Given PO</description>
          </group>
        </group_list>
        <measure>
          <title>6-month Progression-free Survival (PFS) Rate</title>
          <description>Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.</description>
          <population>Eligible, treated and mutation status confirmed</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16" lower_limit="8" upper_limit="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival (PFS)</title>
        <description>PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression.</description>
        <time_frame>Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration</time_frame>
        <population>Eligible, treated and mutation status confirmed</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Palbociclib)</title>
            <description>Patients receive palbociclib 125 mg PO QD days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity&#xD;
Palbociclib: Given PO</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS)</title>
          <description>PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression.</description>
          <population>Eligible, treated and mutation status confirmed</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.8" lower_limit="1.5" upper_limit="2.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration.</time_frame>
      <desc>All patients enrolled were included in the all-cause mortality analysis. Thirty-eight patients were included in the toxicity analysis (excluding two who did not receive treatment).</desc>
      <group_list>
        <group group_id="E1">
          <title>Treatment (Palbociclib)</title>
          <description>Patients receive palbociclib 125 mg PO QD days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity&#xD;
Palbociclib: Given PO</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE 4.0</default_vocab>
        <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="38" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="38"/>
              </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="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death NOS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </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="38"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE 4.0</default_vocab>
        <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="25" subjects_at_risk="38"/>
              </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="12" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Investigations - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </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="5" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="38"/>
              </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>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Statistician</name_or_title>
      <organization>ECOG-ACRIN Cancer Research Group</organization>
      <phone>617-632-3012</phone>
      <email>eatrials@jimmy.harvard.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/NCT04439201
org study id: NCI-2020-03171
secondary id: NCI-2020-03171
secondary id: EAY131-Z1B
secondary id: EAY131-Z1B
secondary id: U10CA180820
secondary id: U24CA196172
nct id: NCT04439201
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II MATCH treatment trial identifies the effects of palbociclib in patients whose
      cancer has genetic changes called CCND1, 2, or 3 amplification. Palbociclib blocks proteins
      called CDK4 and CDK6, which may stop cancer cell growth when CCND1, 2, or 3 amplifications
      are present. Researchers hope to learn if palbociclib will shrink this type of cancer or stop
      its growth.
PRIMARY OBJECTIVE:

      I. To evaluate the proportion of patients with objective response (OR) to targeted study
      agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.

      SECONDARY OBJECTIVES:

      I. To evaluate the proportion of patients alive and progression free at 6 months of treatment
      with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple
      myeloma.

      II. To evaluate time until death or disease progression. III. To identify potential
      predictive biomarkers beyond the genomic alteration by which treatment is assigned or
      resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and
      imaging-based assessment platforms.

      IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes
      from pre- through post-therapy imaging can predict objective response and progression free
      survival and to evaluate the association between pre-treatment radiomic phenotypes and
      targeted gene mutation patterns of tumor biopsy specimens.

      OUTLINE:

      Patients receive palbociclib orally (PO) once daily (QD) on days 1-21. Cycles repeat every 28
      days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months if less than 2
      years from study entry, and then every 6 months for year 3 from study entry.

      THE MATCH SCREENING TRIAL:

      Please see NCT02465060 for information on the MATCH Screening Protocol and applicable
      documents.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate (ORR)
time frame: Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration
description: ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable patients. Objective response is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Details about how to define complete response and partial response can be found in the master protocol. 90% two-sided binomial exact confidence interval is calculated for ORR.
measure: 6-month Progression-free Survival (PFS) Rate
time frame: Assessed at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration, from which 6-month PFS rate is determined
description: Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.
measure: Progression Free Survival (PFS)
time frame: Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration
description: PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression.
arm group label: Treatment (palbociclib)
arm group type: Experimental
description: Patients receive palbociclib 125 mg PO QD days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity
intervention type: Drug
intervention name: Palbociclib
description: Given PO
arm group label: Treatment (palbociclib)
other name: 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one
other name: Ibrance
other name: PD 0332991
other name: PD 332991
other name: PD 991
other name: PD-0332991
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Amy S Clark
role: Principal Investigator
affiliation: ECOG-ACRIN Cancer Research Group
facility: 
country: United States
citation: Clark AS, Hong F, Finn RS, DeMichele AM, Mitchell EP, Zwiebel J, Arnaldez FI, Gray RJ, Wang V, McShane LM, Rubinstein LV, Patton D, Williams PM, Hamilton SR, Copur MS, Kasbari SS, Thind R, Conley BA, Arteaga CL, O'Dwyer PJ, Harris LN, Chen AP, Flaherty KT. Phase II Study of Palbociclib (PD-0332991) in CCND1, 2, or 3 Amplification: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1B. Clin Cancer Res. 2023 Apr 14;29(8):1477-1483. doi: 10.1158/1078-0432.CCR-22-2150.
PMID: 36853016
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Neoplasms
mesh term: Palbociclib
sharing ipd: Yes
ipd description: Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 