<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/NCT02243059</url>
  </required_header>
  <id_info>
    <org_study_id>142030</org_study_id>
    <nct_id>NCT02243059</nct_id>
  </id_info>
  <brief_title>Magnetic Resonance Imaging for Lymph Node Staging in Ovarian Cancer</brief_title>
  <acronym>MILO</acronym>
  <official_title>Contrast Enhanced Diffusion-weighted Magnetic Resonance Imaging for Detection of Pathologic Lymph Nodes in Ovarian Cancer - a Feasibility Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maastricht University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Maastricht University Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Advanced epithelial ovarian cancer has high morbidity and mortality. Patients presenting with&#xD;
      advanced stage ovarian cancer often have cancer spread to regional lymph nodes. Imaging&#xD;
      strategies to depict involved lymph nodes are currently not successful. The purpose of this&#xD;
      study is to evaluate if magnetic resonance imaging (MRI) with gadofosveset trisodium contrast&#xD;
      enhancement (GDF-MRI) and diffusion weighted imaging (DW-MRI) is able to identify involved&#xD;
      lymph nodes in a preoperative setting. This could guide the surgeon during surgery to dissect&#xD;
      lymph nodes which could lead to an optimal diagnosis/staging with the lowest possible&#xD;
      morbidity. We want to determine the optimal imaging settings and feasibility of MRI for the&#xD;
      detection of pathological lymph nodes in women with advanced (FIGO stage IIB-IV) ovarian&#xD;
      cancer undergoing primary debulking surgery and compare this to conventional imaging with&#xD;
      computer tomography (CT).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Problems with availability of study medicine in clinical center&#xD;
  </why_stopped>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">September 2014</completion_date>
  <primary_completion_date type="Actual">September 2014</primary_completion_date>
  <phase>Phase 4</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>Feasibility of MRI in depicting lymph nodes.</measure>
    <time_frame>One year</time_frame>
    <description>Primary outcome measure is to determine the optimal imaging settings and feasibility of MRI combined with DW-MRI and GDF-MRI (gadofosveset-MRI) in the identification of pathologic lymph nodes in women with advanced stage epithelial ovarian cancer.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Diagnostic accuracy of MRI.</measure>
    <time_frame>One year</time_frame>
    <description>Sensitivity, specificity, positive predictive value and negative predictive value for the detection of metastatic lymph nodes will be calculated for MRI (+/- DW-MRI and GDF-MRI) and compared with conventional CT imaging.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Ovarian Neoplasms</condition>
  <arm_group>
    <arm_group_label>GDF-MRI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In this pilot study, all included patients will undergo conventional MRI with contrast enhancement (gadofosveset trisodium) and diffusion weighted MRI.&#xD;
Ablavar™ solution contains 244 mg/mL (0.25 mmol/mL) gadofosveset trisodium. 0.03 mmol/kg of gadofosveset will be administered by manual injection as a single intravenous bolus injection over a period of time up to 30 seconds followed by a 25-30 ml saline flush. In practice, this comes down to the maximum of one vial for one patient (one vial contains 10 ml solution, which contains a total of 2.50 mmol of gadofosveset trisodium equivalent to 2.27 g of gadofosveset).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gadofosveset trisodium (Ablavar™ )</intervention_name>
    <arm_group_label>GDF-MRI</arm_group_label>
    <other_name>Ablavar</other_name>
    <other_name>MS-325</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>MRI</intervention_name>
    <arm_group_label>GDF-MRI</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Non-pregnant female&#xD;
&#xD;
          -  Expected FIGO stage IIB-IV epithelial ovarian carcinoma&#xD;
&#xD;
          -  Scheduled for primary debulking surgery&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  At least 18 years of age.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients estimated to have more benefit from neoadjuvant chemotherapy&#xD;
&#xD;
          -  Ineligibility to undergo MRI&#xD;
&#xD;
               -  Non-MR compatible metallic implants or foreign bodies (ferromagnetic aneurysm&#xD;
                  clip, pacemaker, neurostimulation system, etcetera).&#xD;
&#xD;
               -  Claustrophobia&#xD;
&#xD;
          -  Ineligibility to receive gadofosveset contrast (history of contrast allergy,&#xD;
&#xD;
               -  History of a prior allergic reaction to the active substance or to any of the&#xD;
                  excipients of Ablavar™.&#xD;
&#xD;
               -  Impaired kidney function (Glomerular Filtration Rate &lt;30 ml/min/1.73m2).&#xD;
&#xD;
          -  Previous para-aortic or pelvic lymphadenectomy&#xD;
&#xD;
          -  History of a malignant tumour.&#xD;
&#xD;
          -  Pregnant or lactating patients. Incapacitated subjects&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Toon Van Gorp, Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Maastricht / GROW</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Maastricht</name>
      <address>
        <city>Maastricht</city>
        <zip>6229 HX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <reference>
    <citation>Pereira A, Magrina JF, Rey V, Cortes M, Magtibay PM. Pelvic and aortic lymph node metastasis in epithelial ovarian cancer. Gynecol Oncol. 2007 Jun;105(3):604-8. doi: 10.1016/j.ygyno.2007.01.028. Epub 2007 Feb 23.</citation>
    <PMID>17321572</PMID>
  </reference>
  <reference>
    <citation>Morice P, Joulie F, Camatte S, Atallah D, Rouzier R, Pautier P, Pomel C, Lhomme C, Duvillard P, Castaigne D. Lymph node involvement in epithelial ovarian cancer: analysis of 276 pelvic and paraaortic lymphadenectomies and surgical implications. J Am Coll Surg. 2003 Aug;197(2):198-205. doi: 10.1016/S1072-7515(03)00234-5.</citation>
    <PMID>12892797</PMID>
  </reference>
  <reference>
    <citation>Hoskins WJ, McGuire WP, Brady MF, Homesley HD, Creasman WT, Berman M, Ball H, Berek JS. The effect of diameter of largest residual disease on survival after primary cytoreductive surgery in patients with suboptimal residual epithelial ovarian carcinoma. Am J Obstet Gynecol. 1994 Apr;170(4):974-9; discussion 979-80. doi: 10.1016/s0002-9378(94)70090-7.</citation>
    <PMID>8166218</PMID>
  </reference>
  <reference>
    <citation>Kim HS, Ju W, Jee BC, Kim YB, Park NH, Song YS, Kim SC, Kang SB, Kim JW. Systematic lymphadenectomy for survival in epithelial ovarian cancer: a meta-analysis. Int J Gynecol Cancer. 2010 May;20(4):520-8. doi: 10.1111/IGC.0b013e3181d6de1d.</citation>
    <PMID>20686371</PMID>
  </reference>
  <reference>
    <citation>Maggioni A, Benedetti Panici P, Dell'Anna T, Landoni F, Lissoni A, Pellegrino A, Rossi RS, Chiari S, Campagnutta E, Greggi S, Angioli R, Manci N, Calcagno M, Scambia G, Fossati R, Floriani I, Torri V, Grassi R, Mangioni C. Randomised study of systematic lymphadenectomy in patients with epithelial ovarian cancer macroscopically confined to the pelvis. Br J Cancer. 2006 Sep 18;95(6):699-704. doi: 10.1038/sj.bjc.6603323. Epub 2006 Aug 29.</citation>
    <PMID>16940979</PMID>
  </reference>
  <reference>
    <citation>Onda T, Yoshikawa H, Yokota H, Yasugi T, Taketani Y. Assessment of metastases to aortic and pelvic lymph nodes in epithelial ovarian carcinoma. A proposal for essential sites for lymph node biopsy. Cancer. 1996 Aug 15;78(4):803-8. doi: 10.1002/(SICI)1097-0142(19960815)78:43.0.CO;2-Z.</citation>
    <PMID>8756375</PMID>
  </reference>
  <reference>
    <citation>Kumar Dhingra V, Kand P, Basu S. Impact of FDG-PET and -PET/CT imaging in the clinical decision-making of ovarian carcinoma: an evidence-based approach. Womens Health (Lond). 2012 Mar;8(2):191-203. doi: 10.2217/whe.11.91.</citation>
    <PMID>22375721</PMID>
  </reference>
  <reference>
    <citation>Wakefield JC, Downey K, Kyriazi S, deSouza NM. New MR techniques in gynecologic cancer. AJR Am J Roentgenol. 2013 Feb;200(2):249-60. doi: 10.2214/AJR.12.8932. Erratum In: AJR Am J Roentgenol. 2013 May;200(5):1174.</citation>
    <PMID>23345344</PMID>
  </reference>
  <reference>
    <citation>Lin G, Ho KC, Wang JJ, Ng KK, Wai YY, Chen YT, Chang CJ, Ng SH, Lai CH, Yen TC. Detection of lymph node metastasis in cervical and uterine cancers by diffusion-weighted magnetic resonance imaging at 3T. J Magn Reson Imaging. 2008 Jul;28(1):128-35. doi: 10.1002/jmri.21412.</citation>
    <PMID>18581404</PMID>
  </reference>
  <reference>
    <citation>Yamashita T, Takahara T, Kwee TC, Kawada S, Horie T, Inomoto C, Hashida K, Yamamuro H, Myojin K, Luijten PR, Imai Y. Diffusion magnetic resonance imaging with gadofosveset trisodium as a negative contrast agent for lymph node metastases assessment. Jpn J Radiol. 2011 Jan;29(1):25-32. doi: 10.1007/s11604-010-0513-2. Epub 2011 Jan 26.</citation>
    <PMID>21264658</PMID>
  </reference>
  <reference>
    <citation>Low RN, Barone RM. Combined diffusion-weighted and gadolinium-enhanced MRI can accurately predict the peritoneal cancer index preoperatively in patients being considered for cytoreductive surgical procedures. Ann Surg Oncol. 2012 May;19(5):1394-1401. doi: 10.1245/s10434-012-2236-3.</citation>
    <PMID>22302265</PMID>
  </reference>
  <reference>
    <citation>Lambregts DM, Beets GL, Maas M, Kessels AG, Bakers FC, Cappendijk VC, Engelen SM, Lahaye MJ, de Bruine AP, Lammering G, Leiner T, Verwoerd JL, Wildberger JE, Beets-Tan RG. Accuracy of gadofosveset-enhanced MRI for nodal staging and restaging in rectal cancer. Ann Surg. 2011 Mar;253(3):539-45. doi: 10.1097/SLA.0b013e31820b01f1.</citation>
    <PMID>21239980</PMID>
  </reference>
  <reference>
    <citation>Schipper RJ, Smidt ML, van Roozendaal LM, Castro CJ, de Vries B, Heuts EM, Keymeulen KB, Wildberger JE, Lobbes MB, Beets-Tan RG. Noninvasive nodal staging in patients with breast cancer using gadofosveset-enhanced magnetic resonance imaging: a feasibility study. Invest Radiol. 2013 Mar;48(3):134-9. doi: 10.1097/RLI.0b013e318277f056. Erratum In: Invest Radiol. 2013 May;48(5):332.</citation>
    <PMID>23262788</PMID>
  </reference>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 16, 2014</study_first_submitted>
  <study_first_submitted_qc>September 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 17, 2014</study_first_posted>
  <last_update_submitted>September 24, 2015</last_update_submitted>
  <last_update_submitted_qc>September 24, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 28, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Magnetic Resonance Imaging</keyword>
  <keyword>Gadofosveset trisodium</keyword>
  <keyword>Nodal imaging</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ovarian Neoplasms</mesh_term>
  </condition_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/NCT02243059
org study id: 142030
nct id: NCT02243059
lead sponsor: 
has dmc: Yes
Advanced epithelial ovarian cancer has high morbidity and mortality. Patients presenting with
      advanced stage ovarian cancer often have cancer spread to regional lymph nodes. Imaging
      strategies to depict involved lymph nodes are currently not successful. The purpose of this
      study is to evaluate if magnetic resonance imaging (MRI) with gadofosveset trisodium contrast
      enhancement (GDF-MRI) and diffusion weighted imaging (DW-MRI) is able to identify involved
      lymph nodes in a preoperative setting. This could guide the surgeon during surgery to dissect
      lymph nodes which could lead to an optimal diagnosis/staging with the lowest possible
      morbidity. We want to determine the optimal imaging settings and feasibility of MRI for the
      detection of pathological lymph nodes in women with advanced (FIGO stage IIB-IV) ovarian
      cancer undergoing primary debulking surgery and compare this to conventional imaging with
      computer tomography (CT).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Feasibility of MRI in depicting lymph nodes.
time frame: One year
description: Primary outcome measure is to determine the optimal imaging settings and feasibility of MRI combined with DW-MRI and GDF-MRI (gadofosveset-MRI) in the identification of pathologic lymph nodes in women with advanced stage epithelial ovarian cancer.
measure: Diagnostic accuracy of MRI.
time frame: One year
description: Sensitivity, specificity, positive predictive value and negative predictive value for the detection of metastatic lymph nodes will be calculated for MRI (+/- DW-MRI and GDF-MRI) and compared with conventional CT imaging.
arm group label: GDF-MRI
arm group type: Experimental
description: In this pilot study, all included patients will undergo conventional MRI with contrast enhancement (gadofosveset trisodium) and diffusion weighted MRI.
Ablavar™ solution contains 244 mg/mL (0.25 mmol/mL) gadofosveset trisodium. 0.03 mmol/kg of gadofosveset will be administered by manual injection as a single intravenous bolus injection over a period of time up to 30 seconds followed by a 25-30 ml saline flush. In practice, this comes down to the maximum of one vial for one patient (one vial contains 10 ml solution, which contains a total of 2.50 mmol of gadofosveset trisodium equivalent to 2.27 g of gadofosveset).
intervention type: Drug
intervention name: Gadofosveset trisodium (Ablavar™ )
arm group label: GDF-MRI
other name: Ablavar
other name: MS-325
intervention type: Device
intervention name: MRI
arm group label: GDF-MRI
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Toon Van Gorp, Dr
role: Principal Investigator
affiliation: University Hospital Maastricht / GROW
facility: 
country: Netherlands
citation: Pereira A, Magrina JF, Rey V, Cortes M, Magtibay PM. Pelvic and aortic lymph node metastasis in epithelial ovarian cancer. Gynecol Oncol. 2007 Jun;105(3):604-8. doi: 10.1016/j.ygyno.2007.01.028. Epub 2007 Feb 23.
PMID: 17321572
citation: Morice P, Joulie F, Camatte S, Atallah D, Rouzier R, Pautier P, Pomel C, Lhomme C, Duvillard P, Castaigne D. Lymph node involvement in epithelial ovarian cancer: analysis of 276 pelvic and paraaortic lymphadenectomies and surgical implications. J Am Coll Surg. 2003 Aug;197(2):198-205. doi: 10.1016/S1072-7515(03)00234-5.
PMID: 12892797
citation: Hoskins WJ, McGuire WP, Brady MF, Homesley HD, Creasman WT, Berman M, Ball H, Berek JS. The effect of diameter of largest residual disease on survival after primary cytoreductive surgery in patients with suboptimal residual epithelial ovarian carcinoma. Am J Obstet Gynecol. 1994 Apr;170(4):974-9; discussion 979-80. doi: 10.1016/s0002-9378(94)70090-7.
PMID: 8166218
citation: Kim HS, Ju W, Jee BC, Kim YB, Park NH, Song YS, Kim SC, Kang SB, Kim JW. Systematic lymphadenectomy for survival in epithelial ovarian cancer: a meta-analysis. Int J Gynecol Cancer. 2010 May;20(4):520-8. doi: 10.1111/IGC.0b013e3181d6de1d.
PMID: 20686371
citation: Maggioni A, Benedetti Panici P, Dell'Anna T, Landoni F, Lissoni A, Pellegrino A, Rossi RS, Chiari S, Campagnutta E, Greggi S, Angioli R, Manci N, Calcagno M, Scambia G, Fossati R, Floriani I, Torri V, Grassi R, Mangioni C. Randomised study of systematic lymphadenectomy in patients with epithelial ovarian cancer macroscopically confined to the pelvis. Br J Cancer. 2006 Sep 18;95(6):699-704. doi: 10.1038/sj.bjc.6603323. Epub 2006 Aug 29.
PMID: 16940979
citation: Onda T, Yoshikawa H, Yokota H, Yasugi T, Taketani Y. Assessment of metastases to aortic and pelvic lymph nodes in epithelial ovarian carcinoma. A proposal for essential sites for lymph node biopsy. Cancer. 1996 Aug 15;78(4):803-8. doi: 10.1002/(SICI)1097-0142(19960815)78:43.0.CO;2-Z.
PMID: 8756375
citation: Kumar Dhingra V, Kand P, Basu S. Impact of FDG-PET and -PET/CT imaging in the clinical decision-making of ovarian carcinoma: an evidence-based approach. Womens Health (Lond). 2012 Mar;8(2):191-203. doi: 10.2217/whe.11.91.
PMID: 22375721
citation: Wakefield JC, Downey K, Kyriazi S, deSouza NM. New MR techniques in gynecologic cancer. AJR Am J Roentgenol. 2013 Feb;200(2):249-60. doi: 10.2214/AJR.12.8932. Erratum In: AJR Am J Roentgenol. 2013 May;200(5):1174.
PMID: 23345344
citation: Lin G, Ho KC, Wang JJ, Ng KK, Wai YY, Chen YT, Chang CJ, Ng SH, Lai CH, Yen TC. Detection of lymph node metastasis in cervical and uterine cancers by diffusion-weighted magnetic resonance imaging at 3T. J Magn Reson Imaging. 2008 Jul;28(1):128-35. doi: 10.1002/jmri.21412.
PMID: 18581404
citation: Yamashita T, Takahara T, Kwee TC, Kawada S, Horie T, Inomoto C, Hashida K, Yamamuro H, Myojin K, Luijten PR, Imai Y. Diffusion magnetic resonance imaging with gadofosveset trisodium as a negative contrast agent for lymph node metastases assessment. Jpn J Radiol. 2011 Jan;29(1):25-32. doi: 10.1007/s11604-010-0513-2. Epub 2011 Jan 26.
PMID: 21264658
citation: Low RN, Barone RM. Combined diffusion-weighted and gadolinium-enhanced MRI can accurately predict the peritoneal cancer index preoperatively in patients being considered for cytoreductive surgical procedures. Ann Surg Oncol. 2012 May;19(5):1394-1401. doi: 10.1245/s10434-012-2236-3.
PMID: 22302265
citation: Lambregts DM, Beets GL, Maas M, Kessels AG, Bakers FC, Cappendijk VC, Engelen SM, Lahaye MJ, de Bruine AP, Lammering G, Leiner T, Verwoerd JL, Wildberger JE, Beets-Tan RG. Accuracy of gadofosveset-enhanced MRI for nodal staging and restaging in rectal cancer. Ann Surg. 2011 Mar;253(3):539-45. doi: 10.1097/SLA.0b013e31820b01f1.
PMID: 21239980
citation: Schipper RJ, Smidt ML, van Roozendaal LM, Castro CJ, de Vries B, Heuts EM, Keymeulen KB, Wildberger JE, Lobbes MB, Beets-Tan RG. Noninvasive nodal staging in patients with breast cancer using gadofosveset-enhanced magnetic resonance imaging: a feasibility study. Invest Radiol. 2013 Mar;48(3):134-9. doi: 10.1097/RLI.0b013e318277f056. Erratum In: Invest Radiol. 2013 May;48(5):332.
PMID: 23262788
responsible party type: Sponsor
mesh term: Ovarian Neoplasms