<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/NCT02244502</url>
  </required_header>
  <id_info>
    <org_study_id>EF-22</org_study_id>
    <nct_id>NCT02244502</nct_id>
  </id_info>
  <brief_title>Safety, Feasibility and Effect of TTFields (200 kHz) Concomitant With Weekly Paclitaxel in Recurrent Ovarian Carcinoma (INNOVATE)</brief_title>
  <official_title>An Open Label Pilot Study of the NovoTTF-100L(O) System (NovoTTF Therapy) (200 kHz) Concomitant With Weekly Paclitaxel for Recurrent Ovarian Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NovoCure Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>NovoCure Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study is a prospective, single arm, non-randomized, open label pilot trial, designed to&#xD;
      study the safety, toxicity, feasibility and preliminary efficacy of a medical device, the&#xD;
      NovoTTF-100L(O) concomitant with weekly paclitaxel in recurrent ovarian carcinoma patients.&#xD;
      The device is an experimental, portable, battery operated device for chronic administration&#xD;
      of alternating electric fields (termed TTFields or TTF) to the region of the malignant tumor,&#xD;
      by means of surface, insulated electrode arrays.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PAST PRE CLINICAL AND CLINICAL EXPERIENCE:&#xD;
&#xD;
      The effect of the electric fields generated by the NovoTTF-100L(O) device (Tumor Treating&#xD;
      Fields, TTFields, TTF) has demonstrated significant activity in in vitro and in vivo ovarian&#xD;
      carcinoma pre-clinical models both as a single modality treatment and in combination with&#xD;
      paclitaxel. TTFields has also shown to inhibit metastatic spread of malignant melanoma in in&#xD;
      vivo experiment.&#xD;
&#xD;
      In a small scale pilot study, patients with stage IIIB- IV non-small cell lung cancer (NSCLC)&#xD;
      who had had tumor progression after at least one line of prior chemotherapy received&#xD;
      Pemetrexed together with NovoTTF Therapy applied to the chest and upper abdomen until disease&#xD;
      progression. Efficacy endpoints were remarkably high compared to historical data for&#xD;
      Pemetrexed alone.&#xD;
&#xD;
      In a large prospective, randomized trial, in recurrent glioblastoma (GBM). The outcome of&#xD;
      subjects treated with NovoTTF Therapy was compared to those treated with an effective best&#xD;
      standard of care chemotherapy (including bevacizumab). NovoTTF Therapy subjects had&#xD;
      comparable overall survival to subjects receiving the best available chemotherapy in the US&#xD;
      today. Similar results showing comparability of NovoTTF Therapy to best standard of care&#xD;
      (BSC) chemotherapy were seen in all secondary endpoints. Recurrent GBM patients treated with&#xD;
      the NovoTTF Therapy in this trial experienced fewer side effects in general, significantly&#xD;
      fewer treatment related side effects, and significantly lower gastrointestinal, hematological&#xD;
      and infectious adverse events compared to controls. The only device-related adverse events&#xD;
      seen were a mild to moderate skin irritation beneath the device electrodes. Finally, quality&#xD;
      of life measures were better in NovoTTF Therapy subjects as a group when compared to subjects&#xD;
      receiving effective best standard of care chemotherapy.&#xD;
&#xD;
      DESCRIPTION OF THE TRIAL:&#xD;
&#xD;
      All patients included in this trial are diagnosed with recurrent ovarian carcinoma. In&#xD;
      addition, all patients must meet all eligibility criteria.&#xD;
&#xD;
      Eligible patients will be enrolled, baseline tests will be performed and the patients will be&#xD;
      treated continuously with the device concomitant with weekly paclitaxel until disease&#xD;
      progression.&#xD;
&#xD;
      NovoTTF-100L(O) treatment will consist of wearing four electrically insulated electrode&#xD;
      arrays on the torso. Electrode array placement will require shaving of the abdomen/back as&#xD;
      necessary before and during the treatment. After an initial short visit to the clinic for&#xD;
      training and monitoring, patients will be released to continue treatment at home where they&#xD;
      can maintain their regular daily routine.&#xD;
&#xD;
      During the trial, the patient will need to return once every 4 weeks to the clinic where an&#xD;
      examination by a physician and a routine laboratory examinations will be done. These routine&#xD;
      visits will continue for as long as the patient's disease is not progressing.&#xD;
&#xD;
      During the monthly follow up visits to the clinic patients will be examined physically.&#xD;
      Additionally, routine blood tests will be performed. A routine CT scan of the chest and&#xD;
      abdomen will be performed at baseline and every 8 weeks thereafter, until disease&#xD;
      progression. After this follow up plan, patients will be contacted once per month by&#xD;
      telephone to answer basic questions about their health status.&#xD;
&#xD;
      SCIENTIFIC BACKGROUND:&#xD;
&#xD;
      Electric fields exert forces on electric charges similar to the way a magnet exerts forces on&#xD;
      metallic particles within a magnetic field. These forces cause movement and rotation of&#xD;
      electrically charged biological building blocks, much like the alignment of metallic&#xD;
      particles seen along the lines of force radiating outwards from a magnet.&#xD;
&#xD;
      Electric fields can also cause muscles to twitch and if strong enough may heat tissues.&#xD;
      TTFields are alternating electric fields of low intensity. This means that they change their&#xD;
      direction repetitively many times a second. Since they change direction very rapidly (200&#xD;
      thousand times a second), they do not cause muscles to twitch, nor do they have any effects&#xD;
      on other electrically activated tissues in the body (brain, nerves and heart). Since the&#xD;
      intensities of TTFields in the body are very low, they do not cause heating.&#xD;
&#xD;
      The breakthrough finding made by Novocure was that finely tuned alternating fields of very&#xD;
      low intensity, now termed TTFields (Tumor Treating Fields), cause a significant slowing in&#xD;
      the growth of cancer cells. Due to the unique geometric shape of cancer cells when they are&#xD;
      multiplying, TTFields cause the building blocks of these cells to move and pile up in such a&#xD;
      way that the cells physically explode. In addition, cancer cells also contain miniature&#xD;
      building blocks which act as tiny motors in moving essential parts of the cells from place to&#xD;
      place. TTFields cause these tiny motors to fall apart since they have a special type of&#xD;
      electric charge.&#xD;
&#xD;
      As a result of these two effects, cancer tumor growth is slowed and can even reverse after&#xD;
      continuous exposure to TTFields.&#xD;
&#xD;
      Other cells in the body (normal healthy tissues) are affected much less than cancer cells&#xD;
      since they multiply at a much slower rate if at all. In addition TTFields can be directed to&#xD;
      a certain part of the body, leaving sensitive areas out of their reach.&#xD;
&#xD;
      In conclusion, TTField hold the promise of serving as a brand new cancer treatment with very&#xD;
      few side effects and promising affectivity in slowing or reversing this disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>September 2014</start_date>
  <completion_date type="Anticipated">December 2016</completion_date>
  <primary_completion_date type="Anticipated">December 2016</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse Events Severity and Frequency</measure>
    <time_frame>1.5 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients prematurely discontinuing TTFields due to Skin Toxicity</measure>
    <time_frame>1.5 yeras</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>1.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>1.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>1 Year Survival Rate</measure>
    <time_frame>1.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Radiological Response Rate and Duration of Response</measure>
    <time_frame>1.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CA-125 Response Rate and Duration of Response</measure>
    <time_frame>1.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients' compliance with TTFields Therapy</measure>
    <time_frame>1.5 years</time_frame>
    <description>Patient compliance will be assessed by evaluating the device log file which will be downloaded every 4 weeks from the NovoTTF-100L(O) System. Compliance will be presented as an hourly average over a 24 hour period during the 4 weeks and as an average percentage of use over the 4 week period.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Ovarian Carcinoma</condition>
  <arm_group>
    <arm_group_label>TTFields in combination with weekly paclitaxel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be treated continuously with the NovoTTF-100L(O) device, in addition to weekly paclitaxel.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>NovoTTF-100L(O)</intervention_name>
    <description>Patients will be treated continuously with the NovoTTF-100L(O). NovoTTF-100L(O) treatment will consist of wearing four electrically insulated electrode arrays on the torso. The treatment enables the patient to maintain regular daily routine.</description>
    <arm_group_label>TTFields in combination with weekly paclitaxel</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>Paclitaxel 80 mg/m2 over 1 hour infusion will be administered weekly for 8 weeks and then on days 1, 8, 15 of each subsequent 28 day cycle.</description>
    <arm_group_label>TTFields in combination with weekly paclitaxel</arm_group_label>
    <other_name>Taxol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically or cytologically confirmed ovarian carcinoma, fallopian tube carcinoma&#xD;
             or primary peritoneal carcinoma&#xD;
&#xD;
          2. Recurrent ovarian cancer with any number of prior therapies&#xD;
&#xD;
          3. 18 years of age and older&#xD;
&#xD;
          4. Life expectancy of at least 12 weeks&#xD;
&#xD;
          5. Measurable disease according to the revised RECIST criteria version 1.1. A lesion in a&#xD;
             previously irradiated field is considered &quot;non-measurable&quot; and cannot be a &quot;target&#xD;
             lesion&quot;.&#xD;
&#xD;
          6. ECOG score 0-1 (see Appendix A)&#xD;
&#xD;
          7. Adequate bone marrow, liver and renal functions:&#xD;
&#xD;
               1. Absolute neutrophil count ≥ 1.5 x 10 9/L&#xD;
&#xD;
               2. Platelet count ≥ 100 x 10 9/L&#xD;
&#xD;
               3. Hemoglobin ≥ 10 g/dL&#xD;
&#xD;
               4. AST and/or ALT ≤ 3 x upper limit of normal range (ULN) or ≤ 5 x ULN if patient&#xD;
                  has documented liver metastases&#xD;
&#xD;
               5. Bilirubin ≤1.5 x ULN&#xD;
&#xD;
               6. Serum creatinine ≤ 1.5 x ULN&#xD;
&#xD;
               7. Coagulation status: PT and PTT within normal limits or within therapeutic limits&#xD;
                  for patients receiving anticoagulation.&#xD;
&#xD;
          8. Able to operate the NovoTTF-100L(O) System independently or with the help of a&#xD;
             caregiver&#xD;
&#xD;
          9. No concurrent anti-tumor therapy (beyond weekly paclitaxel and NovoTTF Therapy as per&#xD;
             protocol)&#xD;
&#xD;
         10. At least 4 weeks since major surgery&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Meningeal carcinomatosis or known brain metastases which have not been treated,&#xD;
             require steroid treatment, or are symptomatic.&#xD;
&#xD;
          2. Any other malignancy requiring anti-tumor treatment in the past three years, except&#xD;
             resected non-melanomatous skin cancer, breast carcinoma in situ, adequately treated&#xD;
             stage I breast cancer or in situ cervical cancer.&#xD;
&#xD;
          3. Chemotherapy within 4 weeks prior to treatment start.&#xD;
&#xD;
          4. Radiotherapy within 4 weeks prior to treatment start.&#xD;
&#xD;
          5. Significant comorbidity which is expected to affect patient's prognosis or ability to&#xD;
             receive the combined therapy:&#xD;
&#xD;
               1. History of significant cardiovascular disease unless the disease is well&#xD;
                  controlled. Significant cardiac disease includes second/third degree heart block;&#xD;
                  significant ischemic heart disease; poorly controlled hypertension; congestive&#xD;
                  heart failure of the New York Heart Association (NYHA) Class II or worse (slight&#xD;
                  limitation of physical activity; comfortable at rest, but ordinary activity&#xD;
                  results in fatigue, palpitation or dyspnea).&#xD;
&#xD;
               2. History of arrhythmia that is symptomatic or requires treatment. Patients with&#xD;
                  stable atrial fibrillation or flutter controlled by medication are not excluded&#xD;
                  from participation in the trial.&#xD;
&#xD;
               3. Active infection or any serious underlying medical condition that would impair&#xD;
                  the ability of the patient to receive protocol therapy.&#xD;
&#xD;
               4. History of any psychiatric condition that might impair the patient's ability to&#xD;
                  understand or comply with the requirements of the study or to provide consent.&#xD;
&#xD;
          6. Implantable electronic medical devices including pacemaker, implantable automatic&#xD;
             defibrillator, etc.&#xD;
&#xD;
          7. Known history of sensitivity to taxanes or drugs containing Cremophor&#xD;
&#xD;
          8. Grade 2 or greater peripheral neuropathy&#xD;
&#xD;
          9. Known allergies to medical adhesives or hydrogel&#xD;
&#xD;
         10. Pregnant or breast feeding&#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>Cristina Sessa, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ospedale San Giovanni</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Leuven</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charité - Universitätsmedizin Berlin</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospitale Universitario 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale San Giovanni</name>
      <address>
        <city>Bellinzona</city>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kantonsspital Graubünden</name>
      <address>
        <city>Chur</city>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Germany</country>
    <country>Spain</country>
    <country>Switzerland</country>
  </location_countries>
  <reference>
    <citation>Kirson ED, Gurvich Z, Schneiderman R, Dekel E, Itzhaki A, Wasserman Y, Schatzberger R, Palti Y. Disruption of cancer cell replication by alternating electric fields. Cancer Res. 2004 May 1;64(9):3288-95. doi: 10.1158/0008-5472.can-04-0083.</citation>
    <PMID>15126372</PMID>
  </reference>
  <reference>
    <citation>Kirson ED, Dbaly V, Tovarys F, Vymazal J, Soustiel JF, Itzhaki A, Mordechovich D, Steinberg-Shapira S, Gurvich Z, Schneiderman R, Wasserman Y, Salzberg M, Ryffel B, Goldsher D, Dekel E, Palti Y. Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors. Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10152-7. doi: 10.1073/pnas.0702916104. Epub 2007 Jun 5.</citation>
    <PMID>17551011</PMID>
  </reference>
  <reference>
    <citation>Kirson ED, Giladi M, Gurvich Z, Itzhaki A, Mordechovich D, Schneiderman RS, Wasserman Y, Ryffel B, Goldsher D, Palti Y. Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs. Clin Exp Metastasis. 2009;26(7):633-40. doi: 10.1007/s10585-009-9262-y. Epub 2009 Apr 23.</citation>
    <PMID>19387848</PMID>
  </reference>
  <reference>
    <citation>Pless M, Weinberg U. Tumor treating fields: concept, evidence and future. Expert Opin Investig Drugs. 2011 Aug;20(8):1099-106. doi: 10.1517/13543784.2011.583236. Epub 2011 May 9.</citation>
    <PMID>21548832</PMID>
  </reference>
  <reference>
    <citation>Stupp R, Wong ET, Kanner AA, Steinberg D, Engelhard H, Heidecke V, Kirson ED, Taillibert S, Liebermann F, Dbaly V, Ram Z, Villano JL, Rainov N, Weinberg U, Schiff D, Kunschner L, Raizer J, Honnorat J, Sloan A, Malkin M, Landolfi JC, Payer F, Mehdorn M, Weil RJ, Pannullo SC, Westphal M, Smrcka M, Chin L, Kostron H, Hofer S, Bruce J, Cosgrove R, Paleologous N, Palti Y, Gutin PH. NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer. 2012 Sep;48(14):2192-202. doi: 10.1016/j.ejca.2012.04.011. Epub 2012 May 18.</citation>
    <PMID>22608262</PMID>
  </reference>
  <reference>
    <citation>Pless M, Droege C, von Moos R, Salzberg M, Betticher D. A phase I/II trial of Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer. Lung Cancer. 2013 Sep;81(3):445-450. doi: 10.1016/j.lungcan.2013.06.025. Epub 2013 Jul 23.</citation>
    <PMID>23891283</PMID>
  </reference>
  <reference>
    <citation>Moshe Giladi, Rosa S. Schneiderman, Yaara Porat, Mijal Munster, Aviran Itzhaki, Daniel Mordechovich, Shay Cahal, Uri Weinberg, Eilon D. Kirson, Yoram Palti. Tumor Treating Fields inhibit the growth of pancreatic and ovarian cancer in preclinical models . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5569. doi:10.1158/1538-7445.AM2013-5569</citation>
  </reference>
  <verification_date>July 2016</verification_date>
  <study_first_submitted>September 15, 2014</study_first_submitted>
  <study_first_submitted_qc>September 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 19, 2014</study_first_posted>
  <last_update_submitted>September 20, 2016</last_update_submitted>
  <last_update_submitted_qc>September 20, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 21, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Ovarian Carcinoma</keyword>
  <keyword>Treatment</keyword>
  <keyword>Minimal toxicity</keyword>
  <keyword>TTFields</keyword>
  <keyword>Tumor Treating Fields</keyword>
  <keyword>Novocure</keyword>
  <keyword>Paclitaxel</keyword>
  <keyword>Weekly paclitaxel</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Ovarian Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</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/NCT02244502
org study id: EF-22
nct id: NCT02244502
lead sponsor: 
has dmc: No
The study is a prospective, single arm, non-randomized, open label pilot trial, designed to
      study the safety, toxicity, feasibility and preliminary efficacy of a medical device, the
      NovoTTF-100L(O) concomitant with weekly paclitaxel in recurrent ovarian carcinoma patients.
      The device is an experimental, portable, battery operated device for chronic administration
      of alternating electric fields (termed TTFields or TTF) to the region of the malignant tumor,
      by means of surface, insulated electrode arrays.
PAST PRE CLINICAL AND CLINICAL EXPERIENCE:

      The effect of the electric fields generated by the NovoTTF-100L(O) device (Tumor Treating
      Fields, TTFields, TTF) has demonstrated significant activity in in vitro and in vivo ovarian
      carcinoma pre-clinical models both as a single modality treatment and in combination with
      paclitaxel. TTFields has also shown to inhibit metastatic spread of malignant melanoma in in
      vivo experiment.

      In a small scale pilot study, patients with stage IIIB- IV non-small cell lung cancer (NSCLC)
      who had had tumor progression after at least one line of prior chemotherapy received
      Pemetrexed together with NovoTTF Therapy applied to the chest and upper abdomen until disease
      progression. Efficacy endpoints were remarkably high compared to historical data for
      Pemetrexed alone.

      In a large prospective, randomized trial, in recurrent glioblastoma (GBM). The outcome of
      subjects treated with NovoTTF Therapy was compared to those treated with an effective best
      standard of care chemotherapy (including bevacizumab). NovoTTF Therapy subjects had
      comparable overall survival to subjects receiving the best available chemotherapy in the US
      today. Similar results showing comparability of NovoTTF Therapy to best standard of care
      (BSC) chemotherapy were seen in all secondary endpoints. Recurrent GBM patients treated with
      the NovoTTF Therapy in this trial experienced fewer side effects in general, significantly
      fewer treatment related side effects, and significantly lower gastrointestinal, hematological
      and infectious adverse events compared to controls. The only device-related adverse events
      seen were a mild to moderate skin irritation beneath the device electrodes. Finally, quality
      of life measures were better in NovoTTF Therapy subjects as a group when compared to subjects
      receiving effective best standard of care chemotherapy.

      DESCRIPTION OF THE TRIAL:

      All patients included in this trial are diagnosed with recurrent ovarian carcinoma. In
      addition, all patients must meet all eligibility criteria.

      Eligible patients will be enrolled, baseline tests will be performed and the patients will be
      treated continuously with the device concomitant with weekly paclitaxel until disease
      progression.

      NovoTTF-100L(O) treatment will consist of wearing four electrically insulated electrode
      arrays on the torso. Electrode array placement will require shaving of the abdomen/back as
      necessary before and during the treatment. After an initial short visit to the clinic for
      training and monitoring, patients will be released to continue treatment at home where they
      can maintain their regular daily routine.

      During the trial, the patient will need to return once every 4 weeks to the clinic where an
      examination by a physician and a routine laboratory examinations will be done. These routine
      visits will continue for as long as the patient's disease is not progressing.

      During the monthly follow up visits to the clinic patients will be examined physically.
      Additionally, routine blood tests will be performed. A routine CT scan of the chest and
      abdomen will be performed at baseline and every 8 weeks thereafter, until disease
      progression. After this follow up plan, patients will be contacted once per month by
      telephone to answer basic questions about their health status.

      SCIENTIFIC BACKGROUND:

      Electric fields exert forces on electric charges similar to the way a magnet exerts forces on
      metallic particles within a magnetic field. These forces cause movement and rotation of
      electrically charged biological building blocks, much like the alignment of metallic
      particles seen along the lines of force radiating outwards from a magnet.

      Electric fields can also cause muscles to twitch and if strong enough may heat tissues.
      TTFields are alternating electric fields of low intensity. This means that they change their
      direction repetitively many times a second. Since they change direction very rapidly (200
      thousand times a second), they do not cause muscles to twitch, nor do they have any effects
      on other electrically activated tissues in the body (brain, nerves and heart). Since the
      intensities of TTFields in the body are very low, they do not cause heating.

      The breakthrough finding made by Novocure was that finely tuned alternating fields of very
      low intensity, now termed TTFields (Tumor Treating Fields), cause a significant slowing in
      the growth of cancer cells. Due to the unique geometric shape of cancer cells when they are
      multiplying, TTFields cause the building blocks of these cells to move and pile up in such a
      way that the cells physically explode. In addition, cancer cells also contain miniature
      building blocks which act as tiny motors in moving essential parts of the cells from place to
      place. TTFields cause these tiny motors to fall apart since they have a special type of
      electric charge.

      As a result of these two effects, cancer tumor growth is slowed and can even reverse after
      continuous exposure to TTFields.

      Other cells in the body (normal healthy tissues) are affected much less than cancer cells
      since they multiply at a much slower rate if at all. In addition TTFields can be directed to
      a certain part of the body, leaving sensitive areas out of their reach.

      In conclusion, TTField hold the promise of serving as a brand new cancer treatment with very
      few side effects and promising affectivity in slowing or reversing this disease.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse Events Severity and Frequency
time frame: 1.5 years
measure: Number of patients prematurely discontinuing TTFields due to Skin Toxicity
time frame: 1.5 yeras
measure: Progression Free Survival
time frame: 1.5 years
measure: Overall Survival
time frame: 1.5 years
measure: 1 Year Survival Rate
time frame: 1.5 years
measure: Overall Radiological Response Rate and Duration of Response
time frame: 1.5 years
measure: CA-125 Response Rate and Duration of Response
time frame: 1.5 years
measure: Patients' compliance with TTFields Therapy
time frame: 1.5 years
description: Patient compliance will be assessed by evaluating the device log file which will be downloaded every 4 weeks from the NovoTTF-100L(O) System. Compliance will be presented as an hourly average over a 24 hour period during the 4 weeks and as an average percentage of use over the 4 week period.
arm group label: TTFields in combination with weekly paclitaxel
arm group type: Experimental
description: Patients will be treated continuously with the NovoTTF-100L(O) device, in addition to weekly paclitaxel.
intervention type: Device
intervention name: NovoTTF-100L(O)
description: Patients will be treated continuously with the NovoTTF-100L(O). NovoTTF-100L(O) treatment will consist of wearing four electrically insulated electrode arrays on the torso. The treatment enables the patient to maintain regular daily routine.
arm group label: TTFields in combination with weekly paclitaxel
intervention type: Drug
intervention name: Paclitaxel
description: Paclitaxel 80 mg/m2 over 1 hour infusion will be administered weekly for 8 weeks and then on days 1, 8, 15 of each subsequent 28 day cycle.
arm group label: TTFields in combination with weekly paclitaxel
other name: Taxol
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Cristina Sessa, MD
role: Principal Investigator
affiliation: Ospedale San Giovanni
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belgium
country: Germany
country: Spain
country: Switzerland
citation: Kirson ED, Gurvich Z, Schneiderman R, Dekel E, Itzhaki A, Wasserman Y, Schatzberger R, Palti Y. Disruption of cancer cell replication by alternating electric fields. Cancer Res. 2004 May 1;64(9):3288-95. doi: 10.1158/0008-5472.can-04-0083.
PMID: 15126372
citation: Kirson ED, Dbaly V, Tovarys F, Vymazal J, Soustiel JF, Itzhaki A, Mordechovich D, Steinberg-Shapira S, Gurvich Z, Schneiderman R, Wasserman Y, Salzberg M, Ryffel B, Goldsher D, Dekel E, Palti Y. Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors. Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10152-7. doi: 10.1073/pnas.0702916104. Epub 2007 Jun 5.
PMID: 17551011
citation: Kirson ED, Giladi M, Gurvich Z, Itzhaki A, Mordechovich D, Schneiderman RS, Wasserman Y, Ryffel B, Goldsher D, Palti Y. Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs. Clin Exp Metastasis. 2009;26(7):633-40. doi: 10.1007/s10585-009-9262-y. Epub 2009 Apr 23.
PMID: 19387848
citation: Pless M, Weinberg U. Tumor treating fields: concept, evidence and future. Expert Opin Investig Drugs. 2011 Aug;20(8):1099-106. doi: 10.1517/13543784.2011.583236. Epub 2011 May 9.
PMID: 21548832
citation: Stupp R, Wong ET, Kanner AA, Steinberg D, Engelhard H, Heidecke V, Kirson ED, Taillibert S, Liebermann F, Dbaly V, Ram Z, Villano JL, Rainov N, Weinberg U, Schiff D, Kunschner L, Raizer J, Honnorat J, Sloan A, Malkin M, Landolfi JC, Payer F, Mehdorn M, Weil RJ, Pannullo SC, Westphal M, Smrcka M, Chin L, Kostron H, Hofer S, Bruce J, Cosgrove R, Paleologous N, Palti Y, Gutin PH. NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer. 2012 Sep;48(14):2192-202. doi: 10.1016/j.ejca.2012.04.011. Epub 2012 May 18.
PMID: 22608262
citation: Pless M, Droege C, von Moos R, Salzberg M, Betticher D. A phase I/II trial of Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer. Lung Cancer. 2013 Sep;81(3):445-450. doi: 10.1016/j.lungcan.2013.06.025. Epub 2013 Jul 23.
PMID: 23891283
citation: Moshe Giladi, Rosa S. Schneiderman, Yaara Porat, Mijal Munster, Aviran Itzhaki, Daniel Mordechovich, Shay Cahal, Uri Weinberg, Eilon D. Kirson, Yoram Palti. Tumor Treating Fields inhibit the growth of pancreatic and ovarian cancer in preclinical models . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5569. doi:10.1158/1538-7445.AM2013-5569
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Paclitaxel