<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/NCT02195336</url>
  </required_header>
  <id_info>
    <org_study_id>BevMar</org_study_id>
    <secondary_id>ML29273</secondary_id>
    <nct_id>NCT02195336</nct_id>
  </id_info>
  <brief_title>dMR During First Line Treatment of Non Squamous Lung Cancer: Time Course and Prognostic and Predictive Impact.</brief_title>
  <acronym>BevMar</acronym>
  <official_title>Diffusion MR (dMRT) During First Line Treatment of Non Squamous Lung Cancer With Chemotherapy Combined With Bevacizumab: Time Course and Prognostic and Predictive Impact.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Karl Kölbeck</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Karolinska University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To date, there are no methods to reliably select which patients with non-squamous non-small&#xD;
      cell lung cancer (NSCLC) that benefit most from treatment with bevacizumab. Data have shown&#xD;
      that high levels of plasma VEGF are prognostic and correlates with a worse disease outcome in&#xD;
      some tumour types, including advanced NSCLC.&#xD;
&#xD;
      Recent data are suggestive of a predictive value of imaging techniques for early detection of&#xD;
      antiangiogenic treatment efficacy in different cancers. To our knowledge there are no&#xD;
      presented data available on correlation between changes in diffusion-weighted MR and response&#xD;
      to bevacizumab treatment in lung cancer. The current study is designed as a pilot study to&#xD;
      prospectively investigate changes in MR variables during treatment with bevacizumab and to&#xD;
      detect signals of prognostic and/or predictive value of MR changes during treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A Non Interventional, open-label, single arm, single institution pilot study. Eligible&#xD;
      patients will be monitored by diffusion-weighted magnetic resonance tomography (dMRT) during&#xD;
      treatment with bevacizumab + chemotherapy for up to four cycles followed by bevacizumab&#xD;
      maintenance therapy until disease progression.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>August 2014</start_date>
  <completion_date type="Anticipated">June 2018</completion_date>
  <primary_completion_date type="Anticipated">June 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>dMRT changes during treatment</measure>
    <time_frame>Baseline, Day 8, Day 28, Day 92, At relapse.</time_frame>
    <description>Diffusion magnetic resonance tomography of lung lesions.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response to treatment</measure>
    <time_frame>Baseline, Day 92, at 5, 7, 9, 12, 15, 18, 24 mo during follow up</time_frame>
    <description>CT of lungs, clinical examinations</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>3. Time to disease progression (defined as the time period from the start of first-line therapy to investigator assessed disease progression)</measure>
    <time_frame>Baseline, Day 92, at 5, 7, 9, 12, 15, 18, 24 mo during follow up</time_frame>
    <description>CT, clinical examinations</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of survival</measure>
    <time_frame>At 5, 7, 9, 12, 15, 18, 24, 36 and 48 mo during follow up</time_frame>
    <description>Defined as the time period from the start of first-line therapy to death.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Non-small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>dMRT, Bevacizumab, Chemotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>dMRT: Magnetic Resonance Tomograph, Baseline, day 8, day 28, day 92, progression/relapse.&#xD;
Bevacizumab: 7.5mg/kg every 3 weeks for 3 cycles. Standard of care NSCLC first-line chemotherapy, doublets containing paclitaxel and carboplatin are preferred, every 3 weeks for 3 cycles.&#xD;
Thereafter Bevacizumab 7.5mg/kg every 3 weeks until progression/relapse or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>dMRT</intervention_name>
    <description>Baseline, day 8, day 28, day 92, progression/relapse.</description>
    <arm_group_label>dMRT, Bevacizumab, Chemotherapy</arm_group_label>
    <other_name>Magnetic Resonance Tomograph</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bevacizumab</intervention_name>
    <description>7.5mg/kg every 3 weeks for 3 cycles. Thereafter every 3 weeks until progression/relapse or unacceptable toxicity.</description>
    <arm_group_label>dMRT, Bevacizumab, Chemotherapy</arm_group_label>
    <other_name>Avastin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>paclitaxel and carboplatin</intervention_name>
    <description>Standard of care NSCLC first-line chemotherapy Every 3 weeks for 3 cycles. Doublets containing paclitaxel and carboplatin are preferred</description>
    <arm_group_label>dMRT, Bevacizumab, Chemotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written informed consent obtained prior to any study-specific procedure&#xD;
&#xD;
          2. Age ≥18 years&#xD;
&#xD;
          3. Able to comply with the protocol&#xD;
&#xD;
          4. Histologically or cytologically documented inoperable, metastatic (Stage IV) non small&#xD;
             cell lung cancer&#xD;
&#xD;
          5. ECOG PS status 0-1&#xD;
&#xD;
          6. Life expectancy ≥12 weeks&#xD;
&#xD;
          7. Adequate haematological function:&#xD;
&#xD;
               -  Normal values of absolute neutrophil and platelet count, and a hemoglobin value&#xD;
                  ≥9 g/dL&#xD;
&#xD;
          8. Adequate liver function:&#xD;
&#xD;
               -  Total bilirubin &lt;1.5 x ULN, AST, ALT &lt;2.5 x ULN&#xD;
&#xD;
          9. Adequate renal function:&#xD;
&#xD;
               -  Calculated creatinine clearance ≥50 mL/min, a urine dipstick for proteinuria &lt;2+.&#xD;
&#xD;
         10. Normal values of INR within 7 days prior to enrolment&#xD;
&#xD;
         11. If female, should not be pregnant or breast-feeding. Women with an intact uterus&#xD;
             (unless amenorrhoeic for the last 24 months) must have a negative serum pregnancy test&#xD;
             within 28 days prior to enrolment into the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Mixed, non-small cell and small cell tumours or mixed adenosquamous carcinomas with a&#xD;
             predominant squamous component&#xD;
&#xD;
          2. Known EGFR mutation or ALK translocation&#xD;
&#xD;
          3. History of haemoptysis&#xD;
&#xD;
          4. Evidence of tumour invading major blood vessels on imaging. The investigator or the&#xD;
             local radiologist must exclude evidence of tumour that is fully contiguous with,&#xD;
             surrounding, or extending into the lumen of a major blood vessel (e.g. pulmonary&#xD;
             artery or superior vena cava)&#xD;
&#xD;
          5. Evidence of CNS metastases, even if previously treated. If suspected, the patient&#xD;
             should be scanned within 28 days prior to enrolment to rule out CNS metastases&#xD;
&#xD;
          6. Previous treatment with chemotherapy or other anticancer agent&#xD;
&#xD;
          7. Previous radiotherapy of the primary tumour. Palliative extrathoracic radiotherapy is&#xD;
             allowed prior to enrolment or during treatment&#xD;
&#xD;
          8. Major surgery (including open biopsy), significant traumatic injury within 28 days&#xD;
             prior to enrolment or anticipation of the need for major surgery during study&#xD;
             treatment&#xD;
&#xD;
          9. Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to&#xD;
             the first bevacizumab infusion&#xD;
&#xD;
         10. Current or recent (within 10 days of first dose of bevacizumab) use of aspirin (&gt;&#xD;
             325mg/day) or use of full-dose oral or parenteral anticoagulants or thrombolytic agent&#xD;
             for therapeutic purposes.&#xD;
&#xD;
         11. History or evidence of inherited bleeding diathesis or coagulopathy with the risk of&#xD;
             bleeding&#xD;
&#xD;
         12. Uncontrolled hypertension (systolic &gt;150 mmHg and/or diastolic &gt;100 mmHg)&#xD;
&#xD;
         13. Clinically significant (i.e. active) cardiovascular disease&#xD;
&#xD;
         14. Non-healing wound, active peptic ulcer or bone fracture&#xD;
&#xD;
         15. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess&#xD;
             within 6 months of enrolment&#xD;
&#xD;
         16. Women with an intact uterus (unless amenorrhoeic for the last 24 months) not using&#xD;
             effective, means of contraception during the study and for a period of 6 months&#xD;
             following the last administration of bevacizumab. Men who do not agree to use&#xD;
             effective contraception during the study and for a period of 90 days following the&#xD;
             last administration of bevacizumab. Men who do not agree to use effective&#xD;
             contraception during the study and for a period of 90 days following the last&#xD;
             administration of bevacizumab&#xD;
&#xD;
         17. Treatment with any other investigational agent, or participation in another clinical&#xD;
             trial within 28 days prior to enrolment&#xD;
&#xD;
         18. Known hypersensitivity to bevacizumab or any of its excipients, and any of the&#xD;
             chemotherapies&#xD;
&#xD;
         19. Evidence of ongoing or active infection, any other disease, neurological or metabolic&#xD;
             dysfunction, physical examination finding or laboratory finding giving reasonable&#xD;
             suspicion of a disease or condition that contraindicates the use of an investigational&#xD;
             drug or puts the patient at high risk for treatment-related complications&#xD;
&#xD;
         20. Patients diagnosed with a tracheo-oesophageal fistula&#xD;
&#xD;
         21. History of thrombotic disorders within the last 6 months prior to enrolment.&#xD;
&#xD;
         22. Contraindications for MRI: pacemaker and/or non-MRI compatible metallic&#xD;
             implants/objects/devices/fragments.&#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>Karl-Gustav Kölbeck, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Karolinska University Hospital, Dept of Lung and Allergy</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Karl-Gustav Kölbeck, MD</last_name>
    <phone>+46-8-51774960</phone>
    <email>karl.kolbeck@karolinska.se</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Eeva Alamartimo, RN</last_name>
    <phone>+46-8-51773918</phone>
    <email>eeva.alamartimo@ki.se</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Dept of Lung and Allergy, Karolinska university hospital</name>
      <address>
        <city>Stockholm</city>
        <country>Sweden</country>
      </address>
    </facility>
    <contact>
      <last_name>Karl-Gustav Kölbeck, MD</last_name>
      <phone>+46-8-51774960</phone>
      <email>karl.kolbeck@karolinska.se</email>
    </contact>
    <contact_backup>
      <last_name>Eeva Alamartimo, RN</last_name>
      <phone>+46-8-51773918</phone>
      <email>eeva.alamartimo@ki.se</email>
    </contact_backup>
    <investigator>
      <last_name>Mikael Skorpil, MED</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 14, 2014</study_first_submitted>
  <study_first_submitted_qc>July 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 21, 2014</study_first_posted>
  <last_update_submitted>July 18, 2014</last_update_submitted>
  <last_update_submitted_qc>July 18, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 21, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Karolinska University Hospital</investigator_affiliation>
    <investigator_full_name>Karl Kölbeck</investigator_full_name>
    <investigator_title>MD, Consultant</investigator_title>
  </responsible_party>
  <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>Paclitaxel</mesh_term>
    <mesh_term>Bevacizumab</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT02195336
org study id: BevMar
secondary id: ML29273
nct id: NCT02195336
lead sponsor: 
has dmc: No
To date, there are no methods to reliably select which patients with non-squamous non-small
      cell lung cancer (NSCLC) that benefit most from treatment with bevacizumab. Data have shown
      that high levels of plasma VEGF are prognostic and correlates with a worse disease outcome in
      some tumour types, including advanced NSCLC.

      Recent data are suggestive of a predictive value of imaging techniques for early detection of
      antiangiogenic treatment efficacy in different cancers. To our knowledge there are no
      presented data available on correlation between changes in diffusion-weighted MR and response
      to bevacizumab treatment in lung cancer. The current study is designed as a pilot study to
      prospectively investigate changes in MR variables during treatment with bevacizumab and to
      detect signals of prognostic and/or predictive value of MR changes during treatment.
A Non Interventional, open-label, single arm, single institution pilot study. Eligible
      patients will be monitored by diffusion-weighted magnetic resonance tomography (dMRT) during
      treatment with bevacizumab + chemotherapy for up to four cycles followed by bevacizumab
      maintenance therapy until disease progression.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: dMRT changes during treatment
time frame: Baseline, Day 8, Day 28, Day 92, At relapse.
description: Diffusion magnetic resonance tomography of lung lesions.
measure: Response to treatment
time frame: Baseline, Day 92, at 5, 7, 9, 12, 15, 18, 24 mo during follow up
description: CT of lungs, clinical examinations
measure: 3. Time to disease progression (defined as the time period from the start of first-line therapy to investigator assessed disease progression)
time frame: Baseline, Day 92, at 5, 7, 9, 12, 15, 18, 24 mo during follow up
description: CT, clinical examinations
measure: Duration of survival
time frame: At 5, 7, 9, 12, 15, 18, 24, 36 and 48 mo during follow up
description: Defined as the time period from the start of first-line therapy to death.
arm group label: dMRT, Bevacizumab, Chemotherapy
arm group type: Experimental
description: dMRT: Magnetic Resonance Tomograph, Baseline, day 8, day 28, day 92, progression/relapse.
Bevacizumab: 7.5mg/kg every 3 weeks for 3 cycles. Standard of care NSCLC first-line chemotherapy, doublets containing paclitaxel and carboplatin are preferred, every 3 weeks for 3 cycles.
Thereafter Bevacizumab 7.5mg/kg every 3 weeks until progression/relapse or unacceptable toxicity.
intervention type: Device
intervention name: dMRT
description: Baseline, day 8, day 28, day 92, progression/relapse.
arm group label: dMRT, Bevacizumab, Chemotherapy
other name: Magnetic Resonance Tomograph
intervention type: Drug
intervention name: Bevacizumab
description: 7.5mg/kg every 3 weeks for 3 cycles. Thereafter every 3 weeks until progression/relapse or unacceptable toxicity.
arm group label: dMRT, Bevacizumab, Chemotherapy
other name: Avastin
intervention type: Drug
intervention name: paclitaxel and carboplatin
description: Standard of care NSCLC first-line chemotherapy Every 3 weeks for 3 cycles. Doublets containing paclitaxel and carboplatin are preferred
arm group label: dMRT, Bevacizumab, Chemotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Karl-Gustav Kölbeck, MD
role: Principal Investigator
affiliation: Karolinska University Hospital, Dept of Lung and Allergy
last name: Karl-Gustav Kölbeck, MD
phone: +46-8-51774960
email: karl.kolbeck@karolinska.se
last name: Eeva Alamartimo, RN
phone: +46-8-51773918
email: eeva.alamartimo@ki.se
facility: 
contact: 
contact backup: 
investigator: 
country: Sweden
responsible party type: Sponsor-Investigator
investigator affiliation: Karolinska University Hospital
investigator full name: Karl Kölbeck
investigator title: MD, Consultant
mesh term: Lung Neoplasms
mesh term: Paclitaxel
mesh term: Bevacizumab
mesh term: Carboplatin