xml: <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/NCT06006923</url>
    </required_header>
    <id_info>
      <org_study_id>HCC 23-041</org_study_id>
      <nct_id>NCT06006923</nct_id>
    </id_info>
    <brief_title>Regorafenib in Combination With Pembrolizumab or Pembrolizumab for MSI-H Colorectal Cancer</brief_title>
    <official_title>Randomized Trial of Regorafenib in Combination With Pembrolizumab or Pembrolizumab Monotherapy With an Efficacy Lead-in of Regorafenib and Pembrolizumab for Patients With MSI-H Colorectal Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Ibrahim Halil Sahin</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Bayer</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Pittsburgh</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>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a trial of Regorafenib in combination with pembrolizumab for patients with MSI-H&#xD;
        colorectal cancer consisting of lead-in phase examining preliminary efficacy and safety,&#xD;
        followed by a randomized phase to further examine efficacy.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Regorafenib is a multi-kinase inhibitor that targets several receptor tyrosine kinases&#xD;
        including vascular endothelial growth factor receptor (VEGFR). Regorafenib may also have&#xD;
        immunomodulatory affect in the tumor microenvironment. Preclinical and early clinical studies&#xD;
        indicate there is a potential for synergistic activity of regorafenib with immune checkpoint&#xD;
        inhibitors that can be leveraged to augment antitumor immunity. Pembrolizumab, anti-PD1&#xD;
        blockade, has been approved for patients with high microsatellite instability (MSI-H)&#xD;
        colorectal cancer (CRC) as first line therapy. However, there is still an unmet need to&#xD;
        enhance the efficacy of immune checkpoint inhibitors for patients with MSI-H colorectal&#xD;
        cancer. The efficacy of TKI and immune checkpoint inhibitor combination have been shown in&#xD;
        clinical studies for solid tumors particularly for those that are responsive to immune&#xD;
        checkpoint inhibitors therapy. Therefore, there is strong rationale for the combination of&#xD;
        regorafenib and pembrolizumab in MSI-H colorectal cancer in which there is increased VEGF&#xD;
        activity compared to MSS counterpart. A recent retrospective study showed significantly&#xD;
        improved response to regorafenib among patients with MSI-H colorectal cancer, compared to&#xD;
        patients with MSS colorectal cancer. Collectively, this combination may increase anti-tumor&#xD;
        immune response and clinical effectiveness of immunotherapy for patients with MSI-H&#xD;
        colorectal cancer. Based on prior clinical trials, the target regorafenib dose in this study&#xD;
        is determined to be 90 mg. However, patients in the lead-in phase will receive regorafenib 60&#xD;
        mg in combination with 200mg of pembrolizumab Q3 weeks in the first cycle to increase&#xD;
        tolerance and study compliance. The dose of regorafenib will be increased to 90 mg by Cycle&#xD;
        2. An interim analysis will be performed after completion of data collection for the lead-in&#xD;
        phase. Target enrollment for the lead-in phase is approximately 22 patients. Following the&#xD;
        futility analysis in lead-in phase, the randomized phase target enrollment is determined to&#xD;
        be 66 patients per arm, for a total trial enrollment of 154 participants. Patients who&#xD;
        received 3 or less cycles of chemotherapy prior to the determination of MMR-D and MSI-H&#xD;
        disease can be enrolled in this trial.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">August 2028</completion_date>
    <primary_completion_date type="Anticipated">August 2025</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Objective Response Rate (ORR), Lead-in Phase</measure>
      <time_frame>Up to 12 months (lead-in phase)</time_frame>
      <description>Percentage of patients with partial response (PR) or complete response (CR) to the treatment per RECIST 1.1. criteria. v1.1. Per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or nontarget) with reduction in short axis to &lt;10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Progression-free Survival (PFS), Randomize Phase</measure>
      <time_frame>Up to 24 months</time_frame>
      <description>Median number of months from time of randomization to the date of disease progression or death from any cause. Per RECISIT v1.1: Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Adverse Events and Serious Adverse Events Related to Treatment</measure>
      <time_frame>Up to 24 months (lead-in phase)</time_frame>
      <description>Percentage of patients that experience Adverse Events (AEs) and/or Serious Adverse Events (SAEs) related to study treatment, per NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The maximum grade for each type of toxicity will be recorded for each patient.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adverse Events and Serious Adverse Events Related to Treatment</measure>
      <time_frame>Up to 24 months (beginning at start of post lead-in phase)</time_frame>
      <description>Percentage of patients that experience Adverse Events (AEs) and/or Serious Adverse Events (SAEs) related to study treatment, per NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The maximum grade for each type of toxicity will be recorded for each patient.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free Survival (PFS), Lead-In Phase</measure>
      <time_frame>Up to 24 months</time_frame>
      <description>Median number of months from time of randomization to the date of disease progression or death from any cause. Per RECISIT v1.1: Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Survival (OS)</measure>
      <time_frame>Up to 48 months (lead-in phase)</time_frame>
      <description>Median number of months from start of treatment to death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Survival (OS)</measure>
      <time_frame>Up to 24 months (beginning at start of post lead-in phase)</time_frame>
      <description>Median number of months from time of randomization to death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Objective Response Rate (ORR), Randomized Phase</measure>
      <time_frame>Up to 12 months (beginning at start of post lead-in phase)</time_frame>
      <description>Percentage of patients with partial response (PR) or complete response (CR) to the treatment per RECIST 1.1. criteria. v1.1. Per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or nontarget) with reduction in short axis to &lt;10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">154</enrollment>
    <condition>MSI-H Colorectal Cancer</condition>
    <arm_group>
      <arm_group_label>Pembrolizumab + Regorafenib</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Pembrolizumab: 200mg, Q3 weeks&#xD;
  Regorafenib: 60mg Cycle 1 Day 1 90 mg Cycle 2 Day 1</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Pembrolizumab</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Pembrolizumab: 200mg, Q3 weeks</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Regorafenib</intervention_name>
      <description>A multi-kinase inhibitor that targets several receptor tyrosine kinases including vascular endothelial growth factor receptor (VEGFR), which may also have immunomodulatory affect in the tumor microenvironment.</description>
      <arm_group_label>Pembrolizumab + Regorafenib</arm_group_label>
      <other_name>BAY 73-4506</other_name>
      <other_name>Stivarga</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Pembrolizumab</intervention_name>
      <description>An anti-PD1 blockade / immune checkpoint inhibitor treatment approved for patients with high microsatellite instability (MSI-H) colorectal cancer (CRC) as first line therapy.</description>
      <arm_group_label>Pembrolizumab</arm_group_label>
      <arm_group_label>Pembrolizumab + Regorafenib</arm_group_label>
      <other_name>Keytruda</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Histologically confirmed mismatch repair deficient or microsatellite instability high&#xD;
               advanced stage colorectal cancer&#xD;
  &#xD;
            2. Measurable disease (per RECIST v1.1)&#xD;
  &#xD;
            3. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1&#xD;
  &#xD;
            4. Age &gt; 18&#xD;
  &#xD;
            5. The patient must be able to swallow oral medication.&#xD;
  &#xD;
            6. Adequate organ function based on the following lab assessments:&#xD;
  &#xD;
                 1. ANC must be ≥ 1500/mm3&#xD;
  &#xD;
                 2. platelet count must be ≥ 100,000/mm3&#xD;
  &#xD;
                 3. WBC count ≥ 2.5 × 109 /L&#xD;
  &#xD;
                 4. Hemoglobin must be ≥ 9 g/dL&#xD;
  &#xD;
                 5. Alkaline phosphatase ≤ 2.5× upper limit of normal (ULN) with the exception of&#xD;
                    patients with documented liver or bone metastases who should have ALP ≤ 5.0× ULN&#xD;
  &#xD;
                 6. AST and ALT ≤ 2.5× ULN with the exception of patients with documented liver&#xD;
                    metastases who may have AST and/or ALT ≤ 5.0× ULN&#xD;
  &#xD;
                 7. International normalized ratio (INR) ≤ 1.5 x ULN and partial thromboplastin time&#xD;
                    (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless&#xD;
                    receiving treatment with therapeutic anticoagulation&#xD;
  &#xD;
                 8. Total bilirubin ≤ 1.5× ULN (≤ 3× ULN if Gilbert syndrome present)&#xD;
  &#xD;
                 9. Serum albumin ≥ 2.8 g/dL or 28 g/L&#xD;
  &#xD;
                10. Creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault formula)&#xD;
                    or creatinine ≤ 1.5× ULN&#xD;
  &#xD;
            7. No more than three cycles of prior fluoropyrimidine-based chemotherapy including&#xD;
               folinic acid, fluorouracil, and oxaliplatin (FOLFOX); folinic acid, fluorouracil, and&#xD;
               irinotecan (FOLFIRI); and, folinic acid, fluorouracil, oxaliplatin, and irinotecan&#xD;
               (FOLFOXIRI) excluding adjuvant treatment&#xD;
  &#xD;
            8. Patients (male or female) of reproductive potential must agree to use an effective&#xD;
               method of contraception (as discussed with treating physician) from the time consent&#xD;
               is signed, during study therapy, and for at least 8 weeks after the last dose of study&#xD;
               therapy.&#xD;
  &#xD;
            9. Patients who received no more than 1 cycle of pembrolizumab monotherapy will be still&#xD;
               eligible to be enrolled in lead in phase of the trial&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Prior anti-programmed death 1 (anti-PD-1) or anti-cytotoxic T-lymphocyte-associated&#xD;
               antigen 4 (anti-CTLA-4) based therapy&#xD;
  &#xD;
            2. More than 3 cycles of chemotherapy or progression of disease on first line therapy&#xD;
               excluding adjuvant treatment and any systemic anticancer treatment within 2 weeks or 5&#xD;
               half-lives (whichever is shorter) prior to start of study treatment&#xD;
  &#xD;
            3. Active autoimmune disease&#xD;
  &#xD;
            4. Pregnant or lactating females&#xD;
  &#xD;
            5. Uncontrolled human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or&#xD;
               hepatitis C virus (HCV); patients with undetectable viral load and CD4 count &gt; 200&#xD;
               will be eligible for enrollment&#xD;
  &#xD;
            6. Active untreated brain metastasis&#xD;
  &#xD;
            7. Uncontrolled hypertension (HTN: systolic pressure &gt; 150 mmHg or diastolic pressure &gt;&#xD;
               90 mmHg on repeated measurements) and cardiovascular events within 12 months of start&#xD;
               of treatment&#xD;
  &#xD;
            8. Active infection or chronic infection requiring chronic suppressive antibiotics&#xD;
  &#xD;
            9. No active cancer such as colon cancer other than adenocarcinoma (e.g., sarcoma,&#xD;
               lymphoma, carcinoid) within 1 year&#xD;
  &#xD;
           10. Patients with severe hepatic impairment (Child-Pugh C) are excluded as regorafenib has&#xD;
               not been studied in this population and exposure might be increased in these patients&#xD;
  &#xD;
           11. Major surgical procedure or significant traumatic injury within 28 days before start&#xD;
               of study medication&#xD;
  &#xD;
           12. Non-healing wound, non-healing ulcer, or non-healing bone fracture&#xD;
  &#xD;
           13. Patients with evidence or history of any bleeding diathesis, irrespective of severity&#xD;
  &#xD;
           14. Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of&#xD;
               study medication:&#xD;
  &#xD;
                 1. Major surgical procedure or significant traumatic injury within 28 days before&#xD;
                    start of study medication&#xD;
  &#xD;
                 2. Non-healing wound, non-healing ulcer, or non-healing bone fracture&#xD;
  &#xD;
                 3. Patients with evidence or history of any bleeding diathesis, irrespective of&#xD;
                    severity&#xD;
  &#xD;
                 4. Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the&#xD;
                    start of study medication&#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>Ibrahim H Sahin, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>UPMC Hillman Cancer Center</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Clare Grzejka, RN, BSN</last_name>
      <phone>412-623-4891</phone>
      <email>grzejkac@upmc.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Debra Diecks, RN, BSN</last_name>
      <phone>412-623-8364</phone>
      <email>diecksda@upmc.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>UPMC Hillman Cancer Center</name>
        <address>
          <city>Pittsburgh</city>
          <state>Pennsylvania</state>
          <zip>15232</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Clare Grzejka, RN, BSN</last_name>
        <phone>412-623-4891</phone>
        <email>grzejkac@upmc.edu</email>
      </contact>
      <contact_backup>
        <last_name>Debra Diecks, RN, BSN</last_name>
        <phone>412-623-8364</phone>
        <email>diecksda@upmc.edu</email>
      </contact_backup>
      <investigator>
        <last_name>Ibrahim H Sahin, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 17, 2023</study_first_submitted>
    <study_first_submitted_qc>August 17, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 23, 2023</study_first_posted>
    <last_update_submitted>August 17, 2023</last_update_submitted>
    <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 23, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
      <investigator_full_name>Ibrahim Halil Sahin</investigator_full_name>
      <investigator_title>Assistant Professor Hematology/Oncology.</investigator_title>
    </responsible_party>
    <keyword>multi-kinase inhibitor</keyword>
    <keyword>receptor tyrosine kinases</keyword>
    <keyword>anti-PD1 blockade</keyword>
    <keyword>immune checkpoint inhibitor</keyword>
    <keyword>vascular endothelial growth factor receptor (VEGFR)</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>Pembrolizumab</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06006923
  org study id: HCC 23-041
  nct id: NCT06006923
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  This is a trial of Regorafenib in combination with pembrolizumab for patients with MSI-H
        colorectal cancer consisting of lead-in phase examining preliminary efficacy and safety,
        followed by a randomized phase to further examine efficacy.
  Regorafenib is a multi-kinase inhibitor that targets several receptor tyrosine kinases
        including vascular endothelial growth factor receptor (VEGFR). Regorafenib may also have
        immunomodulatory affect in the tumor microenvironment. Preclinical and early clinical studies
        indicate there is a potential for synergistic activity of regorafenib with immune checkpoint
        inhibitors that can be leveraged to augment antitumor immunity. Pembrolizumab, anti-PD1
        blockade, has been approved for patients with high microsatellite instability (MSI-H)
        colorectal cancer (CRC) as first line therapy. However, there is still an unmet need to
        enhance the efficacy of immune checkpoint inhibitors for patients with MSI-H colorectal
        cancer. The efficacy of TKI and immune checkpoint inhibitor combination have been shown in
        clinical studies for solid tumors particularly for those that are responsive to immune
        checkpoint inhibitors therapy. Therefore, there is strong rationale for the combination of
        regorafenib and pembrolizumab in MSI-H colorectal cancer in which there is increased VEGF
        activity compared to MSS counterpart. A recent retrospective study showed significantly
        improved response to regorafenib among patients with MSI-H colorectal cancer, compared to
        patients with MSS colorectal cancer. Collectively, this combination may increase anti-tumor
        immune response and clinical effectiveness of immunotherapy for patients with MSI-H
        colorectal cancer. Based on prior clinical trials, the target regorafenib dose in this study
        is determined to be 90 mg. However, patients in the lead-in phase will receive regorafenib 60
        mg in combination with 200mg of pembrolizumab Q3 weeks in the first cycle to increase
        tolerance and study compliance. The dose of regorafenib will be increased to 90 mg by Cycle
        2. An interim analysis will be performed after completion of data collection for the lead-in
        phase. Target enrollment for the lead-in phase is approximately 22 patients. Following the
        futility analysis in lead-in phase, the randomized phase target enrollment is determined to
        be 66 patients per arm, for a total trial enrollment of 154 participants. Patients who
        received 3 or less cycles of chemotherapy prior to the determination of MMR-D and MSI-H
        disease can be enrolled in this trial.
  allocation: Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Objective Response Rate (ORR), Lead-in Phase
  time frame: Up to 12 months (lead-in phase)
  description: Percentage of patients with partial response (PR) or complete response (CR) to the treatment per RECIST 1.1. criteria. v1.1. Per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or nontarget) with reduction in short axis to <10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
  measure: Progression-free Survival (PFS), Randomize Phase
  time frame: Up to 24 months
  description: Median number of months from time of randomization to the date of disease progression or death from any cause. Per RECISIT v1.1: Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
  measure: Adverse Events and Serious Adverse Events Related to Treatment
  time frame: Up to 24 months (lead-in phase)
  description: Percentage of patients that experience Adverse Events (AEs) and/or Serious Adverse Events (SAEs) related to study treatment, per NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The maximum grade for each type of toxicity will be recorded for each patient.
  measure: Adverse Events and Serious Adverse Events Related to Treatment
  time frame: Up to 24 months (beginning at start of post lead-in phase)
  description: Percentage of patients that experience Adverse Events (AEs) and/or Serious Adverse Events (SAEs) related to study treatment, per NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The maximum grade for each type of toxicity will be recorded for each patient.
  measure: Progression-free Survival (PFS), Lead-In Phase
  time frame: Up to 24 months
  description: Median number of months from time of randomization to the date of disease progression or death from any cause. Per RECISIT v1.1: Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
  measure: Overall Survival (OS)
  time frame: Up to 48 months (lead-in phase)
  description: Median number of months from start of treatment to death from any cause.
  measure: Overall Survival (OS)
  time frame: Up to 24 months (beginning at start of post lead-in phase)
  description: Median number of months from time of randomization to death from any cause.
  measure: Objective Response Rate (ORR), Randomized Phase
  time frame: Up to 12 months (beginning at start of post lead-in phase)
  description: Percentage of patients with partial response (PR) or complete response (CR) to the treatment per RECIST 1.1. criteria. v1.1. Per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or nontarget) with reduction in short axis to <10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
  arm group label: Pembrolizumab + Regorafenib
  arm group type: Experimental
  description: Pembrolizumab: 200mg, Q3 weeks
  Regorafenib: 60mg Cycle 1 Day 1 90 mg Cycle 2 Day 1
  arm group label: Pembrolizumab
  arm group type: Active Comparator
  description: Pembrolizumab: 200mg, Q3 weeks
  intervention type: Drug
  intervention name: Regorafenib
  description: A multi-kinase inhibitor that targets several receptor tyrosine kinases including vascular endothelial growth factor receptor (VEGFR), which may also have immunomodulatory affect in the tumor microenvironment.
  arm group label: Pembrolizumab + Regorafenib
  other name: BAY 73-4506
  other name: Stivarga
  intervention type: Drug
  intervention name: Pembrolizumab
  description: An anti-PD1 blockade / immune checkpoint inhibitor treatment approved for patients with high microsatellite instability (MSI-H) colorectal cancer (CRC) as first line therapy.
  arm group label: Pembrolizumab
  arm group label: Pembrolizumab + Regorafenib
  other name: Keytruda
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Ibrahim H Sahin, MD
  role: Principal Investigator
  affiliation: UPMC Hillman Cancer Center
  last name: Clare Grzejka, RN, BSN
  phone: 412-623-4891
  email: grzejkac@upmc.edu
  last name: Debra Diecks, RN, BSN
  phone: 412-623-8364
  email: diecksda@upmc.edu
  facility: 
  contact: 
  contact backup: 
  investigator: 
  country: United States
  responsible party type: Sponsor-Investigator
  investigator affiliation: University of Pittsburgh
  investigator full name: Ibrahim Halil Sahin
  investigator title: Assistant Professor Hematology/Oncology.
  mesh term: Colorectal Neoplasms
  mesh term: Pembrolizumab
  sharing ipd: No