<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/NCT04461457</url>
  </required_header>
  <id_info>
    <org_study_id>001-211Astatine</org_study_id>
    <secondary_id>151:2004/26262</secondary_id>
    <secondary_id>S571-03</secondary_id>
    <nct_id>NCT04461457</nct_id>
  </id_info>
  <brief_title>Targeted Radiation Therapy for Ovarian Cancer: Intraperitoneal Treatment With 211-astatine-MX35 F(ab')2</brief_title>
  <official_title>Targeted Radiation Therapy for Ovarian Cancer: Intraperitoneal Treatment With 211-astatine-MX35 F(ab')2</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vastra Gotaland Region</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Swedish Cancer Society</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Swedish Research Council</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sahlgrenska University Hospital, Sweden</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Vastra Gotaland Region</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this alpha-radioimmunotherapy study groups of 3 patients with recurring epithelial ovarian&#xD;
      cancer treated by salvage chemo-therapy and being in complete or good partial remission will&#xD;
      receive one intra peritoneal infusion of 211 astatine (211At)-MX35 F(ab')2 . Patients will&#xD;
      receive a single dose of MX35 F(ab')2 radiolabeled with increasing activity concentration of&#xD;
      211At in 1.0 - 2 L Extraneal® solution starting at an activity concentration of 50&#xD;
      megabecquerel per litre (MBq/L).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      -  Five days prior to therapy the patient is provided with a central intra venous line and&#xD;
           an abdominal catheter will be introduced during laparoscopy. To investigate the access&#xD;
           to the whole abdominal cavity and possible catheter leakage, a 99mTc-colloid, will be&#xD;
           infused intra peritoneally (IP) within 1.0 L of a gluco-polymer (Extraneal®).&#xD;
&#xD;
        -  At the day of treatment vital signs will be measured prior to and after the 30 min&#xD;
           infusion and at least every second hour during the first 6 hours after infusion, daily&#xD;
           for the remainder of the in-hospital stay and at a minimum at 2, 3, 4 and 8 weeks after&#xD;
           the IP infusion. Blood samples will be obtained for pharmacokinetic analyses every hour&#xD;
           after completion of the IP infusion for 8 hours, then every 6 hours, together with&#xD;
           sampling from the i.p. catheter.&#xD;
&#xD;
        -  SPECT imaging of the whole abdominal cavity and thorax including the thyroid may be&#xD;
           performed following completion of the IP infusion and at approx 8 or 20hrs post&#xD;
           infusion.&#xD;
&#xD;
        -  Physical examination and electrocardiogram will be done prior to and 4 weeks after the&#xD;
           IP infusion. Clinical biochemical and hematological parameters will be monitored weekly&#xD;
           after treatment. Blood samples to evaluate immunogenicity as well as cancer antigen-125&#xD;
           (CA-125) will also be taken at 2 and 8 weeks after treatment.&#xD;
&#xD;
        -  The first patient will be observed for at least 4 weeks with any observed toxicity is&#xD;
           Grade 2 or less, before the additional patient is accrued at the dose level.&#xD;
&#xD;
        -  Dosimetry safety criteria: Based upon published data on maximal tolerated absorbed dose&#xD;
           (Gy) recalculated to equivalent dose (Sv) with the assumption that the relative&#xD;
           biological effectiveness (RBE) = 5, a limit for organ doses is defined. If any organ&#xD;
           would reach the defined limit the study will be stopped.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 5, 2005</start_date>
  <completion_date type="Actual">January 19, 2012</completion_date>
  <primary_completion_date type="Actual">March 19, 2011</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>To investigate the pharmacokinetics of the conjugate 211At-MX35 F(ab') 2.&#xD;
Groups of 3 patients will be treated at increasing activity concentrations starting at 50 MBq/L</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum observed concentration (Cmax) of Astatine 211</measure>
    <time_frame>Sampled from +1 hour to +48 hrs post infusion.</time_frame>
    <description>Decay corrected activity concentration in serum, intraperitoneal fluid and urine.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the curve (AUC) of astatine 211 from time of dosing to 48 hrs after dosing</measure>
    <time_frame>Sampled from +1 hour to +48 hrs post infusion.</time_frame>
    <description>Decay corrected activity concentration in serum, intraperitoneal fluid and urine, including actual imaging quantification on gamma-Camera scintigraphy.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Toxicity: hematology, liver, kidney, thyroid function</measure>
    <time_frame>From procedure start (implantation of catheter) to 8 weeks after infusion</time_frame>
    <description>As defined by NCI Common Toxicity Criteria v2.0</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Ovarian Cancer</condition>
  <arm_group>
    <arm_group_label>Intraperitoneal Radioimmunotherapy boost</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Four groups of 3 patients with recurring ovarian cancer treated by salvage chemo-therapy and being in complete or good partial remission will receive one IP dose of 211astatine-MX35 F(ab'2). Starting at 50 MBq/L. Dose escalation 100 Mbq/L, 200 MBq/L and finally 300 MBq/L.</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>211-astatine MX35 F(ab')2</intervention_name>
    <description>Alpha emitting radionuclide 211At conjugated to monoclonal antibody MX35 F(ab')2. Targeting the sodium phosphate transporter (NaPi2b).</description>
    <arm_group_label>Intraperitoneal Radioimmunotherapy boost</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients must have histologically confirmed ovarian or tubal or primary peritoneal&#xD;
             adenocarcinoma.&#xD;
&#xD;
          2. Patients must have a recurrent intraperitoneal cancer and treated by a salvage&#xD;
             chemotherapy to complete or good partial remission&#xD;
&#xD;
          3. The following laboratory and clinical results within 2 weeks prior to first study day:&#xD;
&#xD;
             Absolute neutrophil count (ANC) &gt; 1.5 x 109/L Platelet count &gt; 100 x 109/L Serum&#xD;
             bilirubin &lt; upper limit of normal(ULN) Aspartate aminotransaminase (ASAT) &lt; 1.5 x ULN&#xD;
             Serum aminotransferase (ALAT) &lt; 1.5 x ULN Serum creatinine &lt; 1.5 x upper limit of&#xD;
             normal Thyreoglobulin baseline information Thyroid-stimulating hormone (TSH) baseline&#xD;
             information T4 baseline information&#xD;
&#xD;
          4. Karnofsky performance status &gt; 70.&#xD;
&#xD;
          5. Must understand written and spoken Swedish&#xD;
&#xD;
          6. Before any trial-specific procedures or treatment can be performed, the patient must&#xD;
             give written informed consent for participation in the trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Active parenchymal disease (distant metastasis) (i.e. stage IV International&#xD;
             Federation of Gynecology and Obstetrics (FIGO) classification.&#xD;
&#xD;
          2. Presence of diagnosed extra abdominal metastasis&#xD;
&#xD;
          3. Clinically significant heart disease.&#xD;
&#xD;
          4. Electrocardiographic demonstrating clinically significant arrhythmias.&#xD;
&#xD;
          5. Other serious illnesses, e.g. serious infections requiring antibiotics, coagulation&#xD;
             disorders.&#xD;
&#xD;
          6. Chronic inflammatory bowel disease.&#xD;
&#xD;
          7. Chemotherapy, biologic therapy, or immunotherapy within 4 weeks prior&#xD;
&#xD;
          8. Advanced abdominal adherences.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Sahlgrenska University Hospital, Dept of Oncology</name>
      <address>
        <city>Gothenburg</city>
        <zip>41345</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <results_reference>
    <citation>Andersson H, Cederkrantz E, Back T, Divgi C, Elgqvist J, Himmelman J, Horvath G, Jacobsson L, Jensen H, Lindegren S, Palm S, Hultborn R. Intraperitoneal alpha-particle radioimmunotherapy of ovarian cancer patients: pharmacokinetics and dosimetry of (211)At-MX35 F(ab')2--a phase I study. J Nucl Med. 2009 Jul;50(7):1153-60. doi: 10.2967/jnumed.109.062604. Epub 2009 Jun 12.</citation>
    <PMID>19525452</PMID>
  </results_reference>
  <results_reference>
    <citation>Cederkrantz E, Andersson H, Bernhardt P, Back T, Hultborn R, Jacobsson L, Jensen H, Lindegren S, Ljungberg M, Magnander T, Palm S, Albertsson P. Absorbed Doses and Risk Estimates of (211)At-MX35 F(ab')2 in Intraperitoneal Therapy of Ovarian Cancer Patients. Int J Radiat Oncol Biol Phys. 2015 Nov 1;93(3):569-76. doi: 10.1016/j.ijrobp.2015.07.005. Epub 2015 Jul 11.</citation>
    <PMID>26460999</PMID>
  </results_reference>
  <results_reference>
    <citation>Hallqvist A, Bergmark K, Back T, Andersson H, Dahm-Kahler P, Johansson M, Lindegren S, Jensen H, Jacobsson L, Hultborn R, Palm S, Albertsson P. Intraperitoneal alpha-Emitting Radioimmunotherapy with 211At in Relapsed Ovarian Cancer: Long-Term Follow-up with Individual Absorbed Dose Estimations. J Nucl Med. 2019 Aug;60(8):1073-1079. doi: 10.2967/jnumed.118.220384. Epub 2019 Jan 25.</citation>
    <PMID>30683761</PMID>
  </results_reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>July 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <last_update_submitted>July 2, 2020</last_update_submitted>
  <last_update_submitted_qc>July 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ovarian Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Upun specific request, data could be considered to be shared.</ipd_description>
  </patient_data>
  <!-- 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/NCT04461457
org study id: 001-211Astatine
secondary id: 151:2004/26262
secondary id: S571-03
nct id: NCT04461457
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
In this alpha-radioimmunotherapy study groups of 3 patients with recurring epithelial ovarian
      cancer treated by salvage chemo-therapy and being in complete or good partial remission will
      receive one intra peritoneal infusion of 211 astatine (211At)-MX35 F(ab')2 . Patients will
      receive a single dose of MX35 F(ab')2 radiolabeled with increasing activity concentration of
      211At in 1.0 - 2 L Extraneal® solution starting at an activity concentration of 50
      megabecquerel per litre (MBq/L).
-  Five days prior to therapy the patient is provided with a central intra venous line and
           an abdominal catheter will be introduced during laparoscopy. To investigate the access
           to the whole abdominal cavity and possible catheter leakage, a 99mTc-colloid, will be
           infused intra peritoneally (IP) within 1.0 L of a gluco-polymer (Extraneal®).

        -  At the day of treatment vital signs will be measured prior to and after the 30 min
           infusion and at least every second hour during the first 6 hours after infusion, daily
           for the remainder of the in-hospital stay and at a minimum at 2, 3, 4 and 8 weeks after
           the IP infusion. Blood samples will be obtained for pharmacokinetic analyses every hour
           after completion of the IP infusion for 8 hours, then every 6 hours, together with
           sampling from the i.p. catheter.

        -  SPECT imaging of the whole abdominal cavity and thorax including the thyroid may be
           performed following completion of the IP infusion and at approx 8 or 20hrs post
           infusion.

        -  Physical examination and electrocardiogram will be done prior to and 4 weeks after the
           IP infusion. Clinical biochemical and hematological parameters will be monitored weekly
           after treatment. Blood samples to evaluate immunogenicity as well as cancer antigen-125
           (CA-125) will also be taken at 2 and 8 weeks after treatment.

        -  The first patient will be observed for at least 4 weeks with any observed toxicity is
           Grade 2 or less, before the additional patient is accrued at the dose level.

        -  Dosimetry safety criteria: Based upon published data on maximal tolerated absorbed dose
           (Gy) recalculated to equivalent dose (Sv) with the assumption that the relative
           biological effectiveness (RBE) = 5, a limit for organ doses is defined. If any organ
           would reach the defined limit the study will be stopped.
intervention model: Sequential Assignment
intervention model description: To investigate the pharmacokinetics of the conjugate 211At-MX35 F(ab') 2.
Groups of 3 patients will be treated at increasing activity concentrations starting at 50 MBq/L
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum observed concentration (Cmax) of Astatine 211
time frame: Sampled from +1 hour to +48 hrs post infusion.
description: Decay corrected activity concentration in serum, intraperitoneal fluid and urine.
measure: Area under the curve (AUC) of astatine 211 from time of dosing to 48 hrs after dosing
time frame: Sampled from +1 hour to +48 hrs post infusion.
description: Decay corrected activity concentration in serum, intraperitoneal fluid and urine, including actual imaging quantification on gamma-Camera scintigraphy.
measure: Toxicity: hematology, liver, kidney, thyroid function
time frame: From procedure start (implantation of catheter) to 8 weeks after infusion
description: As defined by NCI Common Toxicity Criteria v2.0
arm group label: Intraperitoneal Radioimmunotherapy boost
arm group type: Experimental
description: Four groups of 3 patients with recurring ovarian cancer treated by salvage chemo-therapy and being in complete or good partial remission will receive one IP dose of 211astatine-MX35 F(ab'2). Starting at 50 MBq/L. Dose escalation 100 Mbq/L, 200 MBq/L and finally 300 MBq/L.
intervention type: Combination Product
intervention name: 211-astatine MX35 F(ab')2
description: Alpha emitting radionuclide 211At conjugated to monoclonal antibody MX35 F(ab')2. Targeting the sodium phosphate transporter (NaPi2b).
arm group label: Intraperitoneal Radioimmunotherapy boost
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
facility: 
country: Sweden
citation: Andersson H, Cederkrantz E, Back T, Divgi C, Elgqvist J, Himmelman J, Horvath G, Jacobsson L, Jensen H, Lindegren S, Palm S, Hultborn R. Intraperitoneal alpha-particle radioimmunotherapy of ovarian cancer patients: pharmacokinetics and dosimetry of (211)At-MX35 F(ab')2--a phase I study. J Nucl Med. 2009 Jul;50(7):1153-60. doi: 10.2967/jnumed.109.062604. Epub 2009 Jun 12.
PMID: 19525452
citation: Cederkrantz E, Andersson H, Bernhardt P, Back T, Hultborn R, Jacobsson L, Jensen H, Lindegren S, Ljungberg M, Magnander T, Palm S, Albertsson P. Absorbed Doses and Risk Estimates of (211)At-MX35 F(ab')2 in Intraperitoneal Therapy of Ovarian Cancer Patients. Int J Radiat Oncol Biol Phys. 2015 Nov 1;93(3):569-76. doi: 10.1016/j.ijrobp.2015.07.005. Epub 2015 Jul 11.
PMID: 26460999
citation: Hallqvist A, Bergmark K, Back T, Andersson H, Dahm-Kahler P, Johansson M, Lindegren S, Jensen H, Jacobsson L, Hultborn R, Palm S, Albertsson P. Intraperitoneal alpha-Emitting Radioimmunotherapy with 211At in Relapsed Ovarian Cancer: Long-Term Follow-up with Individual Absorbed Dose Estimations. J Nucl Med. 2019 Aug;60(8):1073-1079. doi: 10.2967/jnumed.118.220384. Epub 2019 Jan 25.
PMID: 30683761
responsible party type: Sponsor
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
sharing ipd: No
ipd description: Upun specific request, data could be considered to be shared.