<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/NCT02199171</url>
  </required_header>
  <id_info>
    <org_study_id>UCI 13-54 HS# 2014-1188</org_study_id>
    <secondary_id>2014-1188</secondary_id>
    <nct_id>NCT02199171</nct_id>
  </id_info>
  <brief_title>Heated Carboplatin in Treating Patients With Stage II-IV Ovarian, Fallopian Tube, or Peritoneal Cancer</brief_title>
  <official_title>A Phase I Dose-escalation and Pharmacokinetic Study of Hyperthermic Intraoperative Intraperitoneal Chemotherapy (HIPEC) Carboplatin at the Time of Cytoreductive Surgery for the Initial Treatment in Patients With Advanced Ovarian, Fallopian Tube, and Peritoneal Carcinomas.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, Irvine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of California, Irvine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial studies the side effects and best dose of heated carboplatin given into&#xD;
      the abdomen at the time of surgery in treating patients with stage II-IV ovarian, fallopian&#xD;
      tube, or peritoneal cancer. Drugs used in chemotherapy, such as carboplatin, work in&#xD;
      different ways to stop the growth of tumor cells, either by killing the cells, by stopping&#xD;
      them from dividing, or by stopping them from spreading. Heating oxaliplatin and infusing it&#xD;
      directly into the area around the tumor during surgery may kill more tumor cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Objectives:&#xD;
&#xD;
      To determine the maximum tolerated dose (MTD) of carboplatin given as HIPEC for primary&#xD;
      treatment of women with advanced ovarian, peritoneal, and fallopian tube cancers.&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
        1. To determine the dose limiting toxicities of HIPEC carboplatin.&#xD;
&#xD;
        2. To describe the pharmacokinetic profile of HIPEC carboplatin.&#xD;
&#xD;
        3. To quantify changes in tissue temperature during HIPEC and compare to conventional&#xD;
           temperature measures (esophageal and bladder).&#xD;
&#xD;
        4. To describe the extent of thermal damage and DNA platinum adduct formation in tissues&#xD;
           resulting from HIPEC carboplatin.&#xD;
&#xD;
      OUTLINE: This is a dose escalation study.&#xD;
&#xD;
      Patients receive hyperthermic carboplatin intraperitoneally over 60 minutes during the&#xD;
      planned surgical cytoreductive procedure.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 2014</start_date>
  <completion_date type="Actual">October 2017</completion_date>
  <primary_completion_date type="Actual">October 2017</primary_completion_date>
  <phase>Phase 1</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>Maximum tolerated dose (MTD) of HIPEC carboplatin</measure>
    <time_frame>Up to 30 days after study treatment</time_frame>
    <description>MTD of HIPEC carboplatin, defined as the dose level with &lt; 2 patients of 6 experiencing dose-limiting toxicities, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.&#xD;
Identified using the continual reassessment method.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease control rates, scored according to Response Evaluation Criteria in Solid Tumors criteria and consist of complete response, partial response, and stable disease</measure>
    <time_frame>Up to 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>1-year overall survival (OS) rate</measure>
    <time_frame>At 1 year</time_frame>
    <description>For 1-year OS rate, death events will be recorded. One-year OS rate will be defined by the number of participants alive 1 year from the time of study entry.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events assessed using Common Toxicity Criteria version 4.0</measure>
    <time_frame>Up to 30 days after study treatment</time_frame>
    <description>Participants who receive any amount of study drug will be evaluable for toxicity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in pharmacokinetic profile of HIPEC carboplatin</measure>
    <time_frame>Baseline and at 5, 15, 30, 45, and 60 minutes</time_frame>
    <description>Median, range, and interquartile range will be calculated and reported for the amount of carboplatin absorbed from the perfusate, the rate of drug absorption from the peritoneal cavity into the systemic circulation, the 0-to-60 minute area under the curve (AUCs) for peritoneal and plasma platinum concentration curves, the total body clearance, the 0-to-24 hour AUC for filterable platinum in the plasma, and regional advantage. Estimates of population averages will be calculated and reported using 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in tissue temperature during HIPEC compared to conventional temperature measures (esophageal and bladder)</measure>
    <time_frame>Baseline to after completion of HIPEC</time_frame>
    <description>Measured at in situ tumor sites and at esophageal and bladder tissue (controls). Median, range and interquartile range will be calculated and reported for mean and peak temperature. Average within-patient paired differences of mean temperature will be summarized descriptively. Estimates of the population average difference in mean temperature between tumor and control tissue will be calculated and reported with 95% confidence intervals. Frechet or type-II extreme value distributions will be used to model the peak temperature as measured in tumor sites.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Extent of DNA platinum adduct formation in tissues resulting from HIPEC carboplatin</measure>
    <time_frame>After HIPEC but before the subject leaves the operating room (up to 2 hours)</time_frame>
    <description>Platinum levels will be measured by inductively coupled plasma mass spectrometry (ICP-MS). Median, range and interquartile range will be calculated and reported for platinum levels per tumor wet weight and per tumor volume. Estimates of population average platinum level will be calculated and reported with 95% confidence intervals as based on measured values or transformed values and the normal approximation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Thermal damage in tissues resulting from HIPEC carboplatin</measure>
    <time_frame>After HIPEC but before the subject leaves the operating room (up to 2 hours)</time_frame>
    <description>A linear model will be calculated and reported for the regression of log-transformed total depth of destruction on per-patient mean temperature as measured during perfusion at in-situ tumor sites.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>FIGO Stage IIC-IV Ovarian Carcinoma</condition>
  <condition>Fallopian Tube Carcinoma</condition>
  <condition>Peritoneal Carcinoma</condition>
  <arm_group>
    <arm_group_label>HIPEC carboplatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive hyperthermic carboplatin intraperitoneally over 60 minutes during the planned surgical cytoreductive procedure.&#xD;
Doses as appropriate for assigned dose level in 500 cubic centimeters (cc)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>carboplatin</intervention_name>
    <description>Given via HIPEC</description>
    <arm_group_label>HIPEC carboplatin</arm_group_label>
    <other_name>(SP-4-2)-diammine[1,1-cyclobutanedicarboxylato(2--)-O,O']platinum, 1,1-cyclobutanedicarboxylic acid platinum complex</other_name>
    <other_name>19314</other_name>
    <other_name>241240</other_name>
    <other_name>41575-94-4</other_name>
    <other_name>Blastocarb</other_name>
    <other_name>Carboplat</other_name>
    <other_name>Carboplatin Hexal</other_name>
    <other_name>Carboplatino</other_name>
    <other_name>Carbosin</other_name>
    <other_name>Carbosol</other_name>
    <other_name>Carbotec</other_name>
    <other_name>CBDCA</other_name>
    <other_name>cis-diammine(1,1-cyclobutanedicarboxylato) platinum(II)</other_name>
    <other_name>cis-diammine(cyclobutane-1,1-dicarboxylato)platinum</other_name>
    <other_name>cis-diammine(cyclobutanedicarboxylato)platinum II</other_name>
    <other_name>Displata</other_name>
    <other_name>Ercar</other_name>
    <other_name>JM-8</other_name>
    <other_name>Nealorin</other_name>
    <other_name>Novoplatinum</other_name>
    <other_name>Paraplat</other_name>
    <other_name>Paraplatin</other_name>
    <other_name>Paraplatin AQ</other_name>
    <other_name>Paraplatine</other_name>
    <other_name>platinum</other_name>
    <other_name>diammine(1,1-cyclobutanedicarboxylato(2-))-</other_name>
    <other_name>(SP-4-2)</other_name>
    <other_name>Platinwas</other_name>
    <other_name>Ribocarbo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have histologically or cytologically confirmed, known or highly&#xD;
             suspected advanced (International Federation of Gynecology and Obstetrics [FIGO] stage&#xD;
             II-IV) ovarian, primary peritoneal, or fallopian tube cancer, scheduled for primary or&#xD;
             interval cytoreductive surgery&#xD;
&#xD;
          -  If the patient has received pre-operative neoadjuvant chemotherapy, evidence of&#xD;
             response must be documented by at least one of the following: decline in serum&#xD;
             carcinoma antigen (CA)125 level, at least a 30% decrease in the sum of the longest&#xD;
             diameter of target lesions on radiographic imaging, or resolution of ascites or&#xD;
             pleural effusion(s)&#xD;
&#xD;
          -  Women of all races and ethnic groups are eligible for this trial&#xD;
&#xD;
          -  Gynecologic Oncology Group (GOG) performance status =&lt; 2&#xD;
&#xD;
          -  Leukocytes &gt;= 3,000/microliter (mcL)&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1,500/mcL&#xD;
&#xD;
          -  Platelets &gt;= 100,000/mcL&#xD;
&#xD;
          -  Total bilirubin within normal institutional limits&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase&#xD;
             (SGOT))/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase (SGPT))&#xD;
             =&lt; 2.5 x institutional upper limit of normal&#xD;
&#xD;
          -  Creatinine within normal institutional limits OR creatinine clearance &gt;= 60&#xD;
             mL/min/1.73 m^2 for patients with creatinine levels above institutional normal&#xD;
&#xD;
          -  Albumin &gt;= 2.5 mg/dL&#xD;
&#xD;
          -  Patients for whom the diagnosis of high-grade serous or undifferentiated carcinoma of&#xD;
             ovarian, peritoneal, or fallopian tubal origin is confirmed at surgery&#xD;
&#xD;
          -  Surgery achieves either no gross residual disease or optimal cytoreductive status&#xD;
             defined as no single lesion measuring more than 1 cm in its greatest diameter (this&#xD;
             protocol calls for the intentional delay in resection of up to 3 tumors per patient&#xD;
             until the HIPEC procedure is complete; the surgeon will identify these tumors as&#xD;
             easily resectable from a technical and safety aspect)&#xD;
&#xD;
          -  Patients must be stable from cardiopulmonary and hemodynamic standpoints to continue&#xD;
             with prolonged surgery and anesthesia&#xD;
&#xD;
          -  Provision of written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients receiving neo-adjuvant chemotherapy whose disease has progressed following at&#xD;
             least 3 cycles, defined by at least one of the following: clinical deterioration (new&#xD;
             or worsening of existing ascites, carcinomatous ileus, malignant bowel obstruction,&#xD;
             declining performance status), new lesion(s) or increase in maximal diameter of &gt; 20%&#xD;
             of the two largest target lesions, rising CA-125 (an increase of at least 10% of&#xD;
             baseline value that increases over 3 values obtained every 21 days)&#xD;
&#xD;
          -  Cardiac or pulmonary conditions that preclude aggressive cytoreductive surgery&#xD;
&#xD;
          -  Patients found to have non-gynecologic, uterine, or breast primary at surgery&#xD;
&#xD;
          -  Patients with gynecologic malignancy of low-grade serous or borderline histology&#xD;
&#xD;
          -  Patients with sub-optimal resection (any single tumor larger than 1 cm)&#xD;
&#xD;
          -  Patients with core body temperature &gt; 37 degrees Celsius (C) at completion of&#xD;
             cytoreductive surgery and prior to HIPEC&#xD;
&#xD;
          -  Patients who are receiving other investigational therapeutic agents&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements&#xD;
&#xD;
          -  Pregnant women are excluded from this study&#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>Krishnansu Tewari, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, Irvine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Chao Family Comprehensive Cancer Center</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>July 16, 2014</study_first_submitted>
  <study_first_submitted_qc>July 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 24, 2014</study_first_posted>
  <last_update_submitted>January 29, 2020</last_update_submitted>
  <last_update_submitted_qc>January 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 31, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, Irvine</investigator_affiliation>
    <investigator_full_name>Krishnansu</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) carboplatin</keyword>
  <keyword>intraperitoneal (IP) chemotherapy</keyword>
  <keyword>cytoreductive surgery</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carboplatin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT02199171
org study id: UCI 13-54 HS# 2014-1188
secondary id: 2014-1188
nct id: NCT02199171
lead sponsor: 
has dmc: Yes
This phase I trial studies the side effects and best dose of heated carboplatin given into
      the abdomen at the time of surgery in treating patients with stage II-IV ovarian, fallopian
      tube, or peritoneal cancer. Drugs used in chemotherapy, such as carboplatin, work in
      different ways to stop the growth of tumor cells, either by killing the cells, by stopping
      them from dividing, or by stopping them from spreading. Heating oxaliplatin and infusing it
      directly into the area around the tumor during surgery may kill more tumor cells.
Primary Objectives:

      To determine the maximum tolerated dose (MTD) of carboplatin given as HIPEC for primary
      treatment of women with advanced ovarian, peritoneal, and fallopian tube cancers.

      Secondary Objectives:

        1. To determine the dose limiting toxicities of HIPEC carboplatin.

        2. To describe the pharmacokinetic profile of HIPEC carboplatin.

        3. To quantify changes in tissue temperature during HIPEC and compare to conventional
           temperature measures (esophageal and bladder).

        4. To describe the extent of thermal damage and DNA platinum adduct formation in tissues
           resulting from HIPEC carboplatin.

      OUTLINE: This is a dose escalation study.

      Patients receive hyperthermic carboplatin intraperitoneally over 60 minutes during the
      planned surgical cytoreductive procedure.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose (MTD) of HIPEC carboplatin
time frame: Up to 30 days after study treatment
description: MTD of HIPEC carboplatin, defined as the dose level with < 2 patients of 6 experiencing dose-limiting toxicities, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
Identified using the continual reassessment method.
measure: Disease control rates, scored according to Response Evaluation Criteria in Solid Tumors criteria and consist of complete response, partial response, and stable disease
time frame: Up to 1 year
measure: 1-year overall survival (OS) rate
time frame: At 1 year
description: For 1-year OS rate, death events will be recorded. One-year OS rate will be defined by the number of participants alive 1 year from the time of study entry.
measure: Incidence of adverse events assessed using Common Toxicity Criteria version 4.0
time frame: Up to 30 days after study treatment
description: Participants who receive any amount of study drug will be evaluable for toxicity.
measure: Change in pharmacokinetic profile of HIPEC carboplatin
time frame: Baseline and at 5, 15, 30, 45, and 60 minutes
description: Median, range, and interquartile range will be calculated and reported for the amount of carboplatin absorbed from the perfusate, the rate of drug absorption from the peritoneal cavity into the systemic circulation, the 0-to-60 minute area under the curve (AUCs) for peritoneal and plasma platinum concentration curves, the total body clearance, the 0-to-24 hour AUC for filterable platinum in the plasma, and regional advantage. Estimates of population averages will be calculated and reported using 95% confidence intervals.
measure: Changes in tissue temperature during HIPEC compared to conventional temperature measures (esophageal and bladder)
time frame: Baseline to after completion of HIPEC
description: Measured at in situ tumor sites and at esophageal and bladder tissue (controls). Median, range and interquartile range will be calculated and reported for mean and peak temperature. Average within-patient paired differences of mean temperature will be summarized descriptively. Estimates of the population average difference in mean temperature between tumor and control tissue will be calculated and reported with 95% confidence intervals. Frechet or type-II extreme value distributions will be used to model the peak temperature as measured in tumor sites.
measure: Extent of DNA platinum adduct formation in tissues resulting from HIPEC carboplatin
time frame: After HIPEC but before the subject leaves the operating room (up to 2 hours)
description: Platinum levels will be measured by inductively coupled plasma mass spectrometry (ICP-MS). Median, range and interquartile range will be calculated and reported for platinum levels per tumor wet weight and per tumor volume. Estimates of population average platinum level will be calculated and reported with 95% confidence intervals as based on measured values or transformed values and the normal approximation.
measure: Thermal damage in tissues resulting from HIPEC carboplatin
time frame: After HIPEC but before the subject leaves the operating room (up to 2 hours)
description: A linear model will be calculated and reported for the regression of log-transformed total depth of destruction on per-patient mean temperature as measured during perfusion at in-situ tumor sites.
arm group label: HIPEC carboplatin
arm group type: Experimental
description: Patients receive hyperthermic carboplatin intraperitoneally over 60 minutes during the planned surgical cytoreductive procedure.
Doses as appropriate for assigned dose level in 500 cubic centimeters (cc)
intervention type: Drug
intervention name: carboplatin
description: Given via HIPEC
arm group label: HIPEC carboplatin
other name: (SP-4-2)-diammine[1,1-cyclobutanedicarboxylato(2--)-O,O']platinum, 1,1-cyclobutanedicarboxylic acid platinum complex
other name: 19314
other name: 241240
other name: 41575-94-4
other name: Blastocarb
other name: Carboplat
other name: Carboplatin Hexal
other name: Carboplatino
other name: Carbosin
other name: Carbosol
other name: Carbotec
other name: CBDCA
other name: cis-diammine(1,1-cyclobutanedicarboxylato) platinum(II)
other name: cis-diammine(cyclobutane-1,1-dicarboxylato)platinum
other name: cis-diammine(cyclobutanedicarboxylato)platinum II
other name: Displata
other name: Ercar
other name: JM-8
other name: Nealorin
other name: Novoplatinum
other name: Paraplat
other name: Paraplatin
other name: Paraplatin AQ
other name: Paraplatine
other name: platinum
other name: diammine(1,1-cyclobutanedicarboxylato(2-))-
other name: (SP-4-2)
other name: Platinwas
other name: Ribocarbo
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Krishnansu Tewari, MD
role: Principal Investigator
affiliation: University of California, Irvine
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of California, Irvine
investigator full name: Krishnansu
investigator title: Professor
mesh term: Carcinoma
mesh term: Carboplatin
sharing ipd: No