<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/NCT03275194</url>
  </required_header>
  <id_info>
    <org_study_id>INCAN/CI/483/15</org_study_id>
    <nct_id>NCT03275194</nct_id>
  </id_info>
  <brief_title>HIPEC in Ovarian Carcinoma Clinical Stage IIIC and IV During Interval Laparotomy</brief_title>
  <official_title>Hyperthermic Intraperitoneal Chemotherapy in Ovarian Carcinoma Clinical Stage IIIC and IV During Interval Laparotomy. Phase II Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Instituto Nacional de Cancerologia de Mexico</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Instituto Nacional de Cancerologia de Mexico</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Ovarian cancer is the leading cause of gynecological cancer mortality, with no current&#xD;
      screening method effective for early diagnosis, with 75% of advanced stage patients being&#xD;
      detected. Not all patients are candidates for standard treatment, which is primary&#xD;
      cytoreduction followed by adjuvant chemotherapy, due to the advanced process. A subgroup of&#xD;
      patients will receive neoadjuvant chemotherapy followed by interval surgery, which allows&#xD;
      higher rates of optimal cytoreduction with low morbidity and mortality. Hyperthermic&#xD;
      intraperitoneal chemotherapy (HIPEC) is a therapeutic option that is used in pathologies of&#xD;
      peritoneal dissemination, whose morbidity and mortality has been reported in several series&#xD;
      and is promising as a management option for ovarian cancer, so it is necessary to evaluate&#xD;
      morbidity and mortality that conditions this modality of treatment as well as if it impacts&#xD;
      on the quality of life of the patients to whom they are performed, which will allow offering&#xD;
      our patients an option of additional treatment to the standard.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Ovarian cancer ranks seventh in incidence of malignant neoplasms in women younger than 65&#xD;
      years and is the leading cause of cancer death in women in the United States. Due to the&#xD;
      absence of an effective screening method and early symptoms, 70% of the cases are diagnosed&#xD;
      in advanced clinical stage (stage III or IV) and the overall 5-year survival is 30-40%.&#xD;
&#xD;
      The standard treatment of locally advanced ovarian carcinoma is primary cytoreductive surgery&#xD;
      plus adjuvant chemotherapy with carboplatin and taxanes. In cases where it is not possible to&#xD;
      perform primary cytoreductive surgery a treatment option is to start with induction&#xD;
      chemotherapy (three or four cycles), in order to reduce tumor size and volume, after which it&#xD;
      is performed an interval surgery, during which it has been reported that optimal&#xD;
      cytoreduction is achieved in 77-94% of patients, with lower morbidity and mortality than&#xD;
      primary surgery, without oncological compromise. Subsequent to interval surgery three&#xD;
      additional cycles of chemotherapy are applied.&#xD;
&#xD;
      Despite an adequate response to the treatment aforementioned, 70% of patients will recur&#xD;
      within the first two years. Because of this high recurrence rate, other therapeutic&#xD;
      alternatives have been evaluated, among them is hyperthermic intraperitoneal chemotherapy&#xD;
      (HIPEC). Since its first description 20 years ago, the HIPEC associated with cytoreductive&#xD;
      surgery in the treatment of malignant neoplasms (primary or metastatic) in the peritoneal&#xD;
      surface has become the standard of treatment, specifically in patients with peritoneal&#xD;
      pseudomyxoma, peritoneal mesothelioma, and cancer with limited peritoneal involvement. In&#xD;
      ovarian cancer, attempts are being made to determine its usefulness in specific scenarios of&#xD;
      this disease.&#xD;
&#xD;
      The increasing interest in the use of HIPEC in the management of advanced ovarian cancer is&#xD;
      based on the coelomic dissemination of ovarian cancer, which in theory would allow this&#xD;
      modality of treatment to be effective. Moreover, optimal cytoreduction and administration of&#xD;
      intraperitoneal chemotherapy over intravenous (intraperitoneal normothermy) have been shown&#xD;
      to be superior in achieving higher survival rates in randomised trials.&#xD;
&#xD;
      Few groups in the world have studied the use of HIPEC in ovarian cancer, however, studies&#xD;
      have been (and are being conducted) in the following scenarios: a) during primary&#xD;
      cytoreduction, b) during interval laparotomy, c) as consolidation after standard treatment,&#xD;
      d) recurrence of platinum resistant carcinoma and e) in the recurrence of &quot;platinum&#xD;
      sensitive&quot; carcinoma. The morbidity of this procedure reported in different series is 33-39%,&#xD;
      and mortality of 0-9%. The feasibility of the procedure with low rates of morbidity and&#xD;
      mortality has been reported, specially when the treatment is done by a multidisciplinary&#xD;
      group especially trained in HIPEC.&#xD;
&#xD;
      The present project is a Phase II, randomised study whose primary objective is to evaluate&#xD;
      the morbidity, mortality, and quality of life of patients undergoing HIPEC during the surgery&#xD;
      with optimal surgical cytoreduction. One group will be treated with cytoreduction and&#xD;
      adjuvant chemotherapy, while the experimental group will be treated with cytoreduction&#xD;
      followed by HIPEC. Our secondary objectives are the assessment of the disease-free period and&#xD;
      overall survival. The working hypothesis is that the use of HIPEC during interval surgery&#xD;
      will have a morbidity considered as acceptable as reported in the literature without&#xD;
      significant deterioration in the quality of life.&#xD;
&#xD;
      The importance of evaluating this new therapeutic tool is that any of the current treatments&#xD;
      for ovarian cancer have a high rate of recurrence. Based in the evidence, biological&#xD;
      behaviour and pattern of dissemination of ovarian cancer, treatment should incorporate both&#xD;
      systemic and locoregional therapy, because the neoplasm spreads via coelomic, lymphatic and&#xD;
      hematogenous. The use of HIPEC together with the surgical event of cytoreduction could avoid&#xD;
      recurrence and allow us to distinguish those patients who are candidates for this procedure&#xD;
      and their actual benefit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 2, 2017</start_date>
  <completion_date type="Anticipated">December 1, 2026</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2025</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>The data will be evaluated for a external person with the groups labeled as &quot;A&quot; and &quot;B&quot; for all outcomes.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Mortality</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>To assess the mortality associated with the use of intraperitoneal hyperthermic chemotherapy during interval laparotomy.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Impact of quality of life</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>To evaluate the impact on patients' quality of life, which is undergoing intraperitoneal hyperthermic chemotherapy during interval laparotomy. The scales that will be used will be EORTC QLQ-C30 (Ver. 3) and EORTC QLQ-OV28.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Morbility</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>To assess the morbidity associated with the use of intraperitoneal hyperthermic chemotherapy during interval laparotomy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease free survival</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Evaluate disease-free survival.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>up to five years</time_frame>
    <description>Evaluate overall 5 year survival.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>HPEC</condition>
  <condition>Ovarian Cancer</condition>
  <condition>Women's Health: Neoplasm of Ovary</condition>
  <condition>Chemotherapy Effect</condition>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>After achieving a complete cytoreductive surgery (no visible residual disease), the patient will be randomised and if is assigned to this arm does not receive additional treatment and the procedure will be finished.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HIPEC group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After achieving a complete cytoreductive surgery (no visible residual disease), the patient will be randomised and if is assigned to this arm receive a HIPEC procedure with cisplatin and doxorubicin.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>HIPEC</intervention_name>
    <description>Following complete cytoreductive surgery without any evidence of residual disease, the patient will be randomized either HIPEC (intervention) or no-HIPEC (control) in the operative Room. If the arm HIPEC is obtained, then a HIPEC procedure with cisplatin and doxorubicin will be performed. If no-HIPEC (control arm) is assigned then the surgical procedure will be finished.</description>
    <arm_group_label>HIPEC group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients younger than 70 years&#xD;
&#xD;
          2. Patient with a diagnosis of high grade serous carcinoma of the ovary and low-grade&#xD;
             endometrioid corroborated by histopathological study.&#xD;
&#xD;
          3. Clinical stage IIIC and IVA (cytology-positive pleural effusion) who have received&#xD;
             induction chemotherapy 3 or 4 cycles of CARBOPLATIN and PACLITAXEL.&#xD;
&#xD;
          4. Partial response to treatment with chemotherapy and evaluated by computed tomography&#xD;
             (RECIST-see below) and response of at least 50% by serum determination of CA-125&#xD;
             antigen.&#xD;
&#xD;
          5. Signature of informed consent.&#xD;
&#xD;
          6. Optimal cytoreduction with residual tumor less than 2.5 mm during interval surgery&#xD;
&#xD;
          7. ECOG less than or equal to 1&#xD;
&#xD;
          8. Adequate renal, cardiac, hepatic, bone marrow and lung function evaluated&#xD;
             preoperatively with the following parameters:&#xD;
&#xD;
             a) Hb equal to or greater than 10 g / L (pre-treatment transfusion is permitted to&#xD;
             achieve this hemoglobin level) b) Leukocytes Greater than 3000 / mm3 (c) Platelets&#xD;
             equal to or greater than 100 000 / mm3 (d) total bilirubin less than 1.5 times greater&#xD;
             than the normal value e) Hepatic transaminases less than 1.5 times higher than normal&#xD;
             value f) Creatinine &lt;1.2 g / dl. In case of being elevated the measured purification&#xD;
             should be greater than 60mL / min according to Cockroft's formula.&#xD;
&#xD;
             g) Albumin greater than 3gr / dl. h) Left Ventricle Ejection fraction per cardiac&#xD;
             echography greater than 55% 9). Sugarbaker carcinomatosis index less than 20&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with heart failure, ischemic heart disease&#xD;
&#xD;
          2. Previous history of treatment with chemotherapy for some other neoplasia&#xD;
&#xD;
          3. History of neuropsychiatric disease&#xD;
&#xD;
          4. Patients with intra operative bleeding that condition hemodynamic instability.&#xD;
&#xD;
          5. Patient requiring more than 2 intraoperative anastomosis&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Genotypic sex</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rosa A Salcedo-Hernandez, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Instituto Nacional de Cancerologia, Columbia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Cancer Institute of Mexico</name>
      <address>
        <city>Mexico City</city>
        <zip>14080</zip>
        <country>Mexico</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rosa A Salcedo-Hernández, M.Sc</last_name>
      <phone>525534265921</phone>
      <email>rosasalher@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Leonardo S Lino-Silva</last_name>
      <phone>525534265921</phone>
      <email>saul.lino.sil@gmail.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Mexico</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>September 2, 2017</study_first_submitted>
  <study_first_submitted_qc>September 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <last_update_submitted>April 26, 2023</last_update_submitted>
  <last_update_submitted_qc>April 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Instituto Nacional de Cancerologia de Mexico</investigator_affiliation>
    <investigator_full_name>Rosa A. Salcedo</investigator_full_name>
    <investigator_title>Surgical oncologist, Gynecology oncology division</investigator_title>
  </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>Undecided</sharing_ipd>
    <ipd_description>The database without any patient identity data could be accede for anyone asking for.</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/NCT03275194
org study id: INCAN/CI/483/15
nct id: NCT03275194
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Ovarian cancer is the leading cause of gynecological cancer mortality, with no current
      screening method effective for early diagnosis, with 75% of advanced stage patients being
      detected. Not all patients are candidates for standard treatment, which is primary
      cytoreduction followed by adjuvant chemotherapy, due to the advanced process. A subgroup of
      patients will receive neoadjuvant chemotherapy followed by interval surgery, which allows
      higher rates of optimal cytoreduction with low morbidity and mortality. Hyperthermic
      intraperitoneal chemotherapy (HIPEC) is a therapeutic option that is used in pathologies of
      peritoneal dissemination, whose morbidity and mortality has been reported in several series
      and is promising as a management option for ovarian cancer, so it is necessary to evaluate
      morbidity and mortality that conditions this modality of treatment as well as if it impacts
      on the quality of life of the patients to whom they are performed, which will allow offering
      our patients an option of additional treatment to the standard.
Ovarian cancer ranks seventh in incidence of malignant neoplasms in women younger than 65
      years and is the leading cause of cancer death in women in the United States. Due to the
      absence of an effective screening method and early symptoms, 70% of the cases are diagnosed
      in advanced clinical stage (stage III or IV) and the overall 5-year survival is 30-40%.

      The standard treatment of locally advanced ovarian carcinoma is primary cytoreductive surgery
      plus adjuvant chemotherapy with carboplatin and taxanes. In cases where it is not possible to
      perform primary cytoreductive surgery a treatment option is to start with induction
      chemotherapy (three or four cycles), in order to reduce tumor size and volume, after which it
      is performed an interval surgery, during which it has been reported that optimal
      cytoreduction is achieved in 77-94% of patients, with lower morbidity and mortality than
      primary surgery, without oncological compromise. Subsequent to interval surgery three
      additional cycles of chemotherapy are applied.

      Despite an adequate response to the treatment aforementioned, 70% of patients will recur
      within the first two years. Because of this high recurrence rate, other therapeutic
      alternatives have been evaluated, among them is hyperthermic intraperitoneal chemotherapy
      (HIPEC). Since its first description 20 years ago, the HIPEC associated with cytoreductive
      surgery in the treatment of malignant neoplasms (primary or metastatic) in the peritoneal
      surface has become the standard of treatment, specifically in patients with peritoneal
      pseudomyxoma, peritoneal mesothelioma, and cancer with limited peritoneal involvement. In
      ovarian cancer, attempts are being made to determine its usefulness in specific scenarios of
      this disease.

      The increasing interest in the use of HIPEC in the management of advanced ovarian cancer is
      based on the coelomic dissemination of ovarian cancer, which in theory would allow this
      modality of treatment to be effective. Moreover, optimal cytoreduction and administration of
      intraperitoneal chemotherapy over intravenous (intraperitoneal normothermy) have been shown
      to be superior in achieving higher survival rates in randomised trials.

      Few groups in the world have studied the use of HIPEC in ovarian cancer, however, studies
      have been (and are being conducted) in the following scenarios: a) during primary
      cytoreduction, b) during interval laparotomy, c) as consolidation after standard treatment,
      d) recurrence of platinum resistant carcinoma and e) in the recurrence of "platinum
      sensitive" carcinoma. The morbidity of this procedure reported in different series is 33-39%,
      and mortality of 0-9%. The feasibility of the procedure with low rates of morbidity and
      mortality has been reported, specially when the treatment is done by a multidisciplinary
      group especially trained in HIPEC.

      The present project is a Phase II, randomised study whose primary objective is to evaluate
      the morbidity, mortality, and quality of life of patients undergoing HIPEC during the surgery
      with optimal surgical cytoreduction. One group will be treated with cytoreduction and
      adjuvant chemotherapy, while the experimental group will be treated with cytoreduction
      followed by HIPEC. Our secondary objectives are the assessment of the disease-free period and
      overall survival. The working hypothesis is that the use of HIPEC during interval surgery
      will have a morbidity considered as acceptable as reported in the literature without
      significant deterioration in the quality of life.

      The importance of evaluating this new therapeutic tool is that any of the current treatments
      for ovarian cancer have a high rate of recurrence. Based in the evidence, biological
      behaviour and pattern of dissemination of ovarian cancer, treatment should incorporate both
      systemic and locoregional therapy, because the neoplasm spreads via coelomic, lymphatic and
      hematogenous. The use of HIPEC together with the surgical event of cytoreduction could avoid
      recurrence and allow us to distinguish those patients who are candidates for this procedure
      and their actual benefit.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: The data will be evaluated for a external person with the groups labeled as "A" and "B" for all outcomes.
measure: Mortality
time frame: Up to 1 year
description: To assess the mortality associated with the use of intraperitoneal hyperthermic chemotherapy during interval laparotomy.
measure: Impact of quality of life
time frame: Up to 1 year
description: To evaluate the impact on patients' quality of life, which is undergoing intraperitoneal hyperthermic chemotherapy during interval laparotomy. The scales that will be used will be EORTC QLQ-C30 (Ver. 3) and EORTC QLQ-OV28.
measure: Morbility
time frame: Up to 1 year
description: To assess the morbidity associated with the use of intraperitoneal hyperthermic chemotherapy during interval laparotomy.
measure: Disease free survival
time frame: Up to 2 years
description: Evaluate disease-free survival.
measure: Overall survival
time frame: up to five years
description: Evaluate overall 5 year survival.
arm group label: Control group
arm group type: No Intervention
description: After achieving a complete cytoreductive surgery (no visible residual disease), the patient will be randomised and if is assigned to this arm does not receive additional treatment and the procedure will be finished.
arm group label: HIPEC group
arm group type: Experimental
description: After achieving a complete cytoreductive surgery (no visible residual disease), the patient will be randomised and if is assigned to this arm receive a HIPEC procedure with cisplatin and doxorubicin.
intervention type: Procedure
intervention name: HIPEC
description: Following complete cytoreductive surgery without any evidence of residual disease, the patient will be randomized either HIPEC (intervention) or no-HIPEC (control) in the operative Room. If the arm HIPEC is obtained, then a HIPEC procedure with cisplatin and doxorubicin will be performed. If no-HIPEC (control arm) is assigned then the surgical procedure will be finished.
arm group label: HIPEC group
criteria: 
gender: Female
gender based: Yes
gender description: Genotypic sex
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Rosa A Salcedo-Hernandez, MSc
role: Principal Investigator
affiliation: Instituto Nacional de Cancerologia, Columbia
facility: 
status: Recruiting
contact: 
contact backup: 
country: Mexico
responsible party type: Principal Investigator
investigator affiliation: Instituto Nacional de Cancerologia de Mexico
investigator full name: Rosa A. Salcedo
investigator title: Surgical oncologist, Gynecology oncology division
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
sharing ipd: Undecided
ipd description: The database without any patient identity data could be accede for anyone asking for.