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/NCT06007937</url>
    </required_header>
    <id_info>
      <org_study_id>23-131</org_study_id>
      <nct_id>NCT06007937</nct_id>
    </id_info>
    <brief_title>A Study of Lorlatinib in Combination With Ramucirumab in People With Lung Cancer</brief_title>
    <official_title>A Phase 1/2 Study of Combination Lorlatinib and Ramucirumab in Patients With Advanced ALK-rearranged Lung Cancers</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Memorial Sloan Kettering Cancer Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Eli Lilly and Company</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Memorial Sloan Kettering Cancer Center</source>
    <oversight_info>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This study will test the safety of the combination of ramucirumab and lorlatinib. The&#xD;
        researchers will test one or two different doses of lorlatinib in combination with&#xD;
        ramucirumab to find the drug combination dose that causes few or mild side effects in&#xD;
        participants. Once the researchers find this dose, they can test it in future participants to&#xD;
        see if it is effective in treating their metastatic ALK-rearranged NSCLC. The researchers are&#xD;
        also looking to see whether there are specific genes or DNA sequences associated with a&#xD;
        response to treatment with lorlatinib and ramucirumab.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 17, 2023</start_date>
    <completion_date type="Anticipated">August 17, 2028</completion_date>
    <primary_completion_date type="Anticipated">August 17, 2028</primary_completion_date>
    <phase>Phase 1/Phase 2</phase>
    <study_type>Interventional</study_type>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Maximum tolerated dose (MTD) (Phase I)</measure>
      <time_frame>1 year</time_frame>
      <description>Dose limiting toxicities using the NCI Common Terminology Criteria for Adverse Events Version 5 (NCI-CTCAE) will be used to grade toxicities during the trial.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Progression-free survival (Phase II)</measure>
      <time_frame>12 months</time_frame>
      <description>by RECIST</description>
    </primary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">56</enrollment>
    <condition>Non Small Cell Lung Cancer</condition>
    <condition>Metastatic</condition>
    <condition>Recurrent</condition>
    <arm_group>
      <arm_group_label>Lorlatinib and ramucirumab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The phase 1 safety portion of the study will assess whether a dose of lorlatinib 100 mg orally daily and ramucirumab 10 mg/kg intravenous infusion once every three weeks is a tolerable and safe dose. Six patients will be enrolled at this dose level and assessed for dose limiting toxicities (DLTs) for one full cycle (21 days). Once the phase 1 portion of the study is complete, patients will be enrolled in the phase 2 portion of the study, cohort expansion at the MTD. Patients will be enrolled in two patient cohorts: cohort 1, treatment-naïve and cohort 2, patients who have progressed on prior second-generation ALK TKI. A cycle will be 21 days in length. Response to therapy will initially be assessed by interval imaging every 2 cycles.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Lorlatinib</intervention_name>
      <description>Lorlatinib 100 mg orally daily</description>
      <arm_group_label>Lorlatinib and ramucirumab</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Ramucirumab</intervention_name>
      <description>Ramucirumab 10 mg/kg intravenous infusion once every three weeks is a tolerable and safe dose.</description>
      <arm_group_label>Lorlatinib and ramucirumab</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Written informed consent&#xD;
  &#xD;
            -  Age &gt;18 years old&#xD;
  &#xD;
            -  Metastatic or recurrent, biopsy-proven non-small cell lung cancer&#xD;
  &#xD;
            -  ALK fusion identified by next generation sequencing (NGS) or IHC on material obtained&#xD;
               from tumor or plasma&#xD;
  &#xD;
            -  Measurable (RECIST 1.1) indicator lesion not previously irradiated&#xD;
  &#xD;
            -  Karnofsky performance status (KPS) ≥ 70%&#xD;
  &#xD;
            -  Adequate organ function defined as follows: ANC ≥1.5 × 10^9 /L, platelets ≥100 ×&#xD;
               10^9/L, hemoglobin ≥ 9 g/dL, INR ≤ 1.5, PTT or aPTT &lt;1.5x ULN, total bilirubin ≤ 1.5 ×&#xD;
               ULN (Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct&#xD;
               bilirubin within normal limits are permitted), AST ≤ 3 × ULN, ALT ≤ 3 × ULN or ≤ 5 x&#xD;
               ULN in the setting of liver metastases, Cr ≤1.5 ULN or CrCl ≥ 40 mL/min. If Cr is&#xD;
  &#xD;
               ≥ 1.5x ULN, a 24-hr urine collection to calculate creatinine clearance must be&#xD;
               performed&#xD;
  &#xD;
               °The patient's urinary protein is ≤1+ on dipstick or routine urinalysis (UA); if urine&#xD;
               dipstick or routine analysis is ≥2+, a 24-hour urine collection for protein must&#xD;
               demonstrate &lt;1000 mg of protein in 24 hours to allow participation in this protocol).&#xD;
  &#xD;
            -  Patients on full-dose anticoagulation must be on a stable dose of oral anticoagulant&#xD;
               or low molecular weight heparin for a minimum of 14 days prior to trial enrollment&#xD;
               without signs of active bleeding or pathological condition that carries a high risk of&#xD;
               bleeding (eg, tumor invading major vessels or known varices). Patients on warfarin&#xD;
               must have an INR ≤ 3.0&#xD;
  &#xD;
            -  Patients must have recovered (Common Terminology Criteria for Adverse Events [CTCAE]&#xD;
               version 5 Grade ≤1) from the acute effects of prior therapy, except for residual&#xD;
               alopecia or peripheral neuropathy (up to grade 2 allowed)prior to start of therapy&#xD;
  &#xD;
            -  Patients in cohort 1 will be treatment-naïve in the metastatic setting. Prior&#xD;
               treatment with adjuvant chemotherapy is allowed&#xD;
  &#xD;
            -  Patients in cohort 2 will have progressed or be intolerant of at least one second&#xD;
               generation ALK TKI, including alectinib, brigatinib, or ceritinib.&#xD;
  &#xD;
            -  Patients may have received multiple ALK TKIs as well as chemotherapy, but one of these&#xD;
               treatments must have been with a second-generation ALK TKI.&#xD;
  &#xD;
            -  Because the teratogenicity of ramucirumab is not known, the patient, if sexually&#xD;
               active, must be postmenopausal, surgically sterile, or using effective contraception&#xD;
               (hormonal or barrier methods).&#xD;
  &#xD;
            -  Female patients of childbearing potential must have a negative serum pregnancy test&#xD;
               within 7 days prior to first dose of protocol therapy.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Prior lorlatinib or ramucirumab exposure&#xD;
  &#xD;
            -  Symptomatic, unstable brain metastasis requiring therapy with steroids or radiation&#xD;
               therapy. Patients with clinically stable brain metastases (previously treated or&#xD;
               untreated) are eligible&#xD;
  &#xD;
            -  Women who are breastfeeding or pregnant&#xD;
  &#xD;
            -  Major radiotherapy within 2 weeks of starting treatment on protocol&#xD;
  &#xD;
            -  Major surgery within 4 weeks of starting treatment on protocol or minor&#xD;
               surgery/subcutaneous venous access device placement within 7 days prior to the first&#xD;
               dose of protocol therapy&#xD;
  &#xD;
            -  Less than 3 weeks since previous chemotherapy, 4 weeks since immunotherapy, and 2&#xD;
               weeks from any investigational therapy&#xD;
  &#xD;
            -  Significant bleeding disorders or grade ≥3 bleeding episode within 12 weeks prior to&#xD;
               enrollment. Patients with history of gross hemoptysis (defined as bright red blood of&#xD;
               ≥1/2 teaspoon) within 8 weeks prior to enrollment will be excluded&#xD;
  &#xD;
            -  New or history of diagnosis of deep vein thrombosis (DVT) or pulmonary embolism (PE)&#xD;
               or other significant thromboembolic event in the 12 weeks prior to first dose of&#xD;
               protocol therapy. Patients with thromboembolic events diagnosed &gt;12 weeks prior to&#xD;
               protocol therapy are eligible if on stable doses of anticoagulation as outlined above.&#xD;
               Venous port or catheter thrombosis or superficial venous thrombosis are not considered&#xD;
               significant events&#xD;
  &#xD;
            -  GI perforation and/or fistula or bowel obstruction within 6 months or risk factors for&#xD;
               perforation prior to enrollment&#xD;
  &#xD;
            -  Child-Pugh B or greater cirrhosis or cirrhosis (any degree) and a history of hepatic&#xD;
               encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically&#xD;
               meaningful ascites is defined as ascites from cirrhosis requiring diuretics or&#xD;
               paracentesis&#xD;
  &#xD;
            -  Uncontrolled hypertension, defined as systolic BP ≥160 mm Hg or diastolic BP ≥100 mm&#xD;
               Hg, prior to initiating study treatment, despite hypertensive intervention&#xD;
  &#xD;
            -  Serious or non-healing wound, ulcer or bone fracture within 28 days of enrollment&#xD;
  &#xD;
            -  Radiologically documented evidence of major blood vessel invasion or encasement by&#xD;
               cancer or radiographic evidence of intratumor cavitation&#xD;
  &#xD;
            -  Active systemic bacterial infection (requiring intravenous [IV] antibiotics at time of&#xD;
               initiating study treatment), fungal infection, or detectable viral infection (such as&#xD;
               known human immunodeficiency virus positivity with known active hepatitis B or C [for&#xD;
               example, hepatitis B surface antigen positive]. Screening is not required for&#xD;
               enrollment.&#xD;
  &#xD;
            -  Arterial thrombotic event or arterial thromboembolic event, including myocardial&#xD;
               infarction, unstable angina, congestive heart failure ≥ NYHA class III,&#xD;
               cerebrovascular accident or transient ischemic attack, within 6 months prior to&#xD;
               enrollment&#xD;
  &#xD;
            -  Planned elective or major surgery during the trial&#xD;
  &#xD;
            -  Chronic therapy with any of the following within 7 days of enrollment:&#xD;
  &#xD;
                 -  Antiplatelet agents (such as clopidogrel, ticlopidine, dipyridamole, or&#xD;
                    anagrelide)&#xD;
  &#xD;
                 -  Aspirin up to 325 mg/day is permitted&#xD;
  &#xD;
            -  Serious uncontrolled medical disorders or psychological conditions that would, in the&#xD;
               opinion of the investigator, limit the patient's ability to complete the study or sign&#xD;
               an informed consent document&#xD;
  &#xD;
            -  Patients with unavoidable strong CYP3A inducer or inhibitor use (see table 15.4 for&#xD;
               list of agents)&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>19 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Gregory Riely, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Gregory Riely, MD, PhD</last_name>
      <phone>646-608-3913</phone>
      <email>rielyg@mskcc.org</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Alexander Drilon, MD</last_name>
      <phone>646-608-3758</phone>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Memorial Sloan Kettering Monmouth (All Protocol Activities)</name>
        <address>
          <city>Middletown</city>
          <state>New Jersey</state>
          <zip>07748</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Gregory Riely, MD, PhD</last_name>
        <phone>646-608-3913</phone>
      </contact>
    </location>
    <location>
      <facility>
        <name>Memorial Sloan Kettering Bergen (All Protocol Activities)</name>
        <address>
          <city>Montvale</city>
          <state>New Jersey</state>
          <zip>07645</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Gregory Riely, MD, PhD</last_name>
        <phone>646-608-3913</phone>
      </contact>
    </location>
    <location>
      <facility>
        <name>Memorial Sloan Kettering Cancer Center Suffolk - Commack (All Protocol Activities)</name>
        <address>
          <city>Commack</city>
          <state>New York</state>
          <zip>11725</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Gregory Riely, MD, PhD</last_name>
        <phone>646-608-3913</phone>
      </contact>
    </location>
    <location>
      <facility>
        <name>Memorial Sloan Kettering West Harrison (All Protocol Activities)</name>
        <address>
          <city>Harrison</city>
          <state>New York</state>
          <zip>10604</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Gregory Riely, MD, PhD</last_name>
        <phone>646-608-3913</phone>
      </contact>
    </location>
    <location>
      <facility>
        <name>Memorial Sloan Kettering Cancer Center (All Protocol Activities)</name>
        <address>
          <city>New York</city>
          <state>New York</state>
          <zip>10065</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Gregory Riely, MD, PhD</last_name>
        <phone>646-608-3913</phone>
      </contact>
      <contact_backup>
        <last_name>Alexander Drilon, MD</last_name>
        <phone>646-608-3758</phone>
      </contact_backup>
      <investigator>
        <last_name>Gregory Riely, MD, PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Memorial Sloan Kettering Nassau (All Protocol Activities)</name>
        <address>
          <city>Rockville Centre</city>
          <state>New York</state>
          <zip>11570</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Gregory Riely, MD, PhD</last_name>
        <phone>646-608-3913</phone>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <link>
      <url>http://www.mskcc.org/mskcc/html/44.cfm</url>
      <description>Memorial Sloan Kettering Cancer Center</description>
    </link>
    <verification_date>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</responsible_party_type>
    </responsible_party>
    <keyword>Lorlatinib</keyword>
    <keyword>Ramucirumab</keyword>
    <keyword>23-131</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lung Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Ramucirumab</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
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/NCT06007937
  org study id: 23-131
  nct id: NCT06007937
  lead sponsor: 
  collaborator: 
  is fda regulated drug: Yes
  is fda regulated device: No
  This study will test the safety of the combination of ramucirumab and lorlatinib. The
        researchers will test one or two different doses of lorlatinib in combination with
        ramucirumab to find the drug combination dose that causes few or mild side effects in
        participants. Once the researchers find this dose, they can test it in future participants to
        see if it is effective in treating their metastatic ALK-rearranged NSCLC. The researchers are
        also looking to see whether there are specific genes or DNA sequences associated with a
        response to treatment with lorlatinib and ramucirumab.
  allocation: N/A
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Maximum tolerated dose (MTD) (Phase I)
  time frame: 1 year
  description: Dose limiting toxicities using the NCI Common Terminology Criteria for Adverse Events Version 5 (NCI-CTCAE) will be used to grade toxicities during the trial.
  measure: Progression-free survival (Phase II)
  time frame: 12 months
  description: by RECIST
  arm group label: Lorlatinib and ramucirumab
  arm group type: Experimental
  description: The phase 1 safety portion of the study will assess whether a dose of lorlatinib 100 mg orally daily and ramucirumab 10 mg/kg intravenous infusion once every three weeks is a tolerable and safe dose. Six patients will be enrolled at this dose level and assessed for dose limiting toxicities (DLTs) for one full cycle (21 days). Once the phase 1 portion of the study is complete, patients will be enrolled in the phase 2 portion of the study, cohort expansion at the MTD. Patients will be enrolled in two patient cohorts: cohort 1, treatment-naïve and cohort 2, patients who have progressed on prior second-generation ALK TKI. A cycle will be 21 days in length. Response to therapy will initially be assessed by interval imaging every 2 cycles.
  intervention type: Drug
  intervention name: Lorlatinib
  description: Lorlatinib 100 mg orally daily
  arm group label: Lorlatinib and ramucirumab
  intervention type: Drug
  intervention name: Ramucirumab
  description: Ramucirumab 10 mg/kg intravenous infusion once every three weeks is a tolerable and safe dose.
  arm group label: Lorlatinib and ramucirumab
  criteria: 
  gender: All
  minimum age: 19 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Gregory Riely, MD, PhD
  role: Principal Investigator
  affiliation: Memorial Sloan Kettering Cancer Center
  last name: Gregory Riely, MD, PhD
  phone: 646-608-3913
  email: rielyg@mskcc.org
  last name: Alexander Drilon, MD
  phone: 646-608-3758
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  investigator: 
  facility: 
  status: Recruiting
  contact: 
  country: United States
  url: http://www.mskcc.org/mskcc/html/44.cfm
  description: Memorial Sloan Kettering Cancer Center
  responsible party type: Sponsor
  mesh term: Lung Neoplasms
  mesh term: Ramucirumab
  sharing ipd: Yes
  ipd description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.