<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/NCT03757858</url>
  </required_header>
  <id_info>
    <org_study_id>RF8-ACT</org_study_id>
    <nct_id>NCT03757858</nct_id>
  </id_info>
  <brief_title>Hyperthermia Combined With Immunotherapy in the Treatment of Abdominal and Pelvic Malignancies or Metastases</brief_title>
  <official_title>A Prospective Study of Hyperthermia Combined With Autologous Adoptive Cellular Immunotherapy in the Treatment of Abdominal and Pelvic Malignancies or Metastases</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Capital Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Capital Medical University</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>
      It is a non-randomized pilot study.The allocation will be determined by patients or their&#xD;
      immediate family members who were cooperative with physician's interpretations on the disease&#xD;
      progression and updated information of cutting of edge treatment, the financial&#xD;
      affordability, availability of treatment plans, possible tolerance or risks etc.The purpose&#xD;
      of this study is to investigate the clinical efficacy and toxicity of autologous cellular&#xD;
      immunotherapy combined with hyperthermia in abdominal and pelvic malignancies or metastases&#xD;
      patients. Furthermore, to characterize response to different regimens,the investigators&#xD;
      intent to explore the predictive and prognostic biomarker, as well as the changes in immune&#xD;
      repertoire.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 1, 2018</start_date>
  <completion_date type="Anticipated">June 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2020</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>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety (adverse events)</measure>
    <time_frame>12 months</time_frame>
    <description>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>6 months</time_frame>
    <description>Proportion of patients with reduction in tumor burden of a predefined amount</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival of the participants(PFS)</measure>
    <time_frame>12 months</time_frame>
    <description>From starting date of the enrollment until the date of first documented disease progression or date of death from any cause, whichever comes first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of Patient- Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)</measure>
    <time_frame>12 months</time_frame>
    <description>To assess and compare the PRO-CTCAE by patients in each groups</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Cancer</condition>
  <condition>Abdominal Cancer</condition>
  <condition>Pelvic Cancer</condition>
  <condition>Metastatic Cancer</condition>
  <condition>Peritoneal Metastases</condition>
  <condition>Liver Metastases</condition>
  <arm_group>
    <arm_group_label>HT+ACT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>HT+ACT+PD-1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>HT+ACT+CT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>HT+CT</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Thermotron RF-8</intervention_name>
    <description>Hyperthermia for 40 minutes, with maximum temperature setted on 42℃ ± 0.5℃ as upper limit, twice a week for a total of 10 times.</description>
    <arm_group_label>HT+ACT</arm_group_label>
    <arm_group_label>HT+ACT+CT</arm_group_label>
    <arm_group_label>HT+ACT+PD-1</arm_group_label>
    <arm_group_label>HT+CT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Adoptive cellular Immunotherapy</intervention_name>
    <description>Mononuclear cells were collected from 50ml peripheral blood , and cultured cytokine-induced killer cells for 15-20 days. Cells were infused back to the patients in 3 times via intravenous infusion .Patients will received at least 2 cycles of CIK Immunotherapy . If the evaluation of the treatment is complete response, partial response or stable disease, additional cycles were eligible.</description>
    <arm_group_label>HT+ACT</arm_group_label>
    <arm_group_label>HT+ACT+CT</arm_group_label>
    <arm_group_label>HT+ACT+PD-1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anti-PD-1 antibody</intervention_name>
    <description>Patients will receive pembrolizumab 100mg every three weeks and assess the clinical outcome every 2 dosage of anti-PD-1 antibody treatment.</description>
    <arm_group_label>HT+ACT+PD-1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Chemotherapy</intervention_name>
    <description>Patients will receive standard chemotherapy until disease progression, unacceptable toxicity or patient refusal.</description>
    <arm_group_label>HT+ACT+CT</arm_group_label>
    <arm_group_label>HT+CT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Abdominal and pelvic malignancies or metastases&#xD;
&#xD;
          2. Estimated life expectancy &gt; 3 months&#xD;
&#xD;
          3. Age ≥ 18 years old&#xD;
&#xD;
          4. At least one measurable lesion according to the Solid Tumor Evaluation Criteria&#xD;
             (RECIST Version 1.1)&#xD;
&#xD;
          5. Adequate hematologic function, with WBC ≥ 3000/microliter, hemoglobin ≥ 9 g/dL (it is&#xD;
             acceptable to have had prior transfusion), platelets ≥ 75,000/microliter; PT-INR &lt;1.5&#xD;
             (unless patient is receiving warfarin in which case PT-INR must be &lt;3), PTT &lt;1.5X ULN&#xD;
&#xD;
          6. Adequate renal and hepatic function, with serum creatinine &lt; 1.5 mg/dL, bilirubin &lt;&#xD;
             1.5 mg/dL (except for Gilbert's syndrome which will allow bilirubin ≤ 2.0 mg/dL), ALT&#xD;
             and AST ≤ 2.5 x upper limit of normal.&#xD;
&#xD;
          7. Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with a history of autoimmune disease, such as but not restricted to,&#xD;
             inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis,&#xD;
             scleroderma, or multiple sclerosis. Autoimmune related thyroid disease and vitiligo&#xD;
             are permitted.&#xD;
&#xD;
          2. Patients with serious intercurrent chronic or acute illness, such as cardiac disease&#xD;
             (NYHA class III or IV), hepatic disease, or other illness considered by the Principal&#xD;
             Investigator as unwarranted high risk for investigational drug treatment.&#xD;
&#xD;
          3. Patients with a medical or psychological impediment to probable compliance with the&#xD;
             protocol should be excluded.&#xD;
&#xD;
          4. Concurrent (or within the last 5 years) second malignancy other than non melanoma skin&#xD;
             cancer, cervical carcinoma in situ, controlled superficial bladder cancer, or other&#xD;
             carcinoma in situ that has been treated.&#xD;
&#xD;
          5. Presence of an active acute or chronic infection including: a urinary tract infection,&#xD;
             HIV (as determined by ELISA and confirmed by Western Blot). Patients with HIV are&#xD;
             excluded based on immuno-suppression, which may render them unable to respond to the&#xD;
             vaccine; patients with chronic hepatitis are excluded because of concern that&#xD;
             hepatitis could be exacerbated by the injections.&#xD;
&#xD;
          6. Patients on chronic steroid therapy (or other immuno-suppressives, such as&#xD;
             azathioprine or cyclosporin A) are excluded on the basis of potential immune&#xD;
             suppression. Patients must have had 6 weeks of discontinuation of any steroid therapy&#xD;
             (except that used as pre-medication for chemotherapy or contrast-enhanced studies or&#xD;
             for acute treatment (&lt;5 days) of intercurrent medical condition such as a gout flare)&#xD;
             prior to enrollment.&#xD;
&#xD;
          7. Pregnant and nursing women should be excluded from the protocol since this research&#xD;
             may have unknown and harmful effects on an unborn child or on young children. If the&#xD;
             patient is sexually active, the patient must agree to use a medically acceptable form&#xD;
             of birth control while receiving treatment and for a period of 4 months following the&#xD;
             last vaccination therapy. It is not known whether the treatment used in this study&#xD;
             could affect the sperm and could potentially harm a child that may be fathered while&#xD;
             on this study.&#xD;
&#xD;
          8. Patients with acute or chronic skin disorders that will interfere with injection into&#xD;
             the skin of the extremities or subsequent assessment of potential skin reactions will&#xD;
             be excluded.&#xD;
&#xD;
          9. There are metal stents or metal fixtures in the body&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Jun Ren, MD,PhD</last_name>
    <phone>86-10-63926317</phone>
    <email>renjun9688@yahoo.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Capital Medical Unvierstiy Cancer Center/ Beijing Shijitan Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100038</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jun Ren, MD,PhD</last_name>
      <phone>86-10-63926317</phone>
      <email>renjun9688@yahoo.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>November 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>July 14, 2020</last_update_submitted>
  <last_update_submitted_qc>July 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 15, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Capital Medical University</investigator_affiliation>
    <investigator_full_name>Jun Ren MD, PhD</investigator_full_name>
    <investigator_title>Director,Capital Medical University (CMU)Cancer Center</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Neoplasms, Second Primary</mesh_term>
    <mesh_term>Pelvic Neoplasms</mesh_term>
    <mesh_term>Hyperthermia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antibodies</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03757858
org study id: RF8-ACT
nct id: NCT03757858
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
It is a non-randomized pilot study.The allocation will be determined by patients or their
      immediate family members who were cooperative with physician's interpretations on the disease
      progression and updated information of cutting of edge treatment, the financial
      affordability, availability of treatment plans, possible tolerance or risks etc.The purpose
      of this study is to investigate the clinical efficacy and toxicity of autologous cellular
      immunotherapy combined with hyperthermia in abdominal and pelvic malignancies or metastases
      patients. Furthermore, to characterize response to different regimens,the investigators
      intent to explore the predictive and prognostic biomarker, as well as the changes in immune
      repertoire.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Safety (adverse events)
time frame: 12 months
description: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
measure: Objective response rate (ORR)
time frame: 6 months
description: Proportion of patients with reduction in tumor burden of a predefined amount
measure: Progression-free survival of the participants(PFS)
time frame: 12 months
description: From starting date of the enrollment until the date of first documented disease progression or date of death from any cause, whichever comes first.
measure: Assessment of Patient- Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
time frame: 12 months
description: To assess and compare the PRO-CTCAE by patients in each groups
arm group label: HT+ACT
arm group type: Experimental
arm group label: HT+ACT+PD-1
arm group type: Experimental
arm group label: HT+ACT+CT
arm group type: Experimental
arm group label: HT+CT
arm group type: Active Comparator
intervention type: Device
intervention name: Thermotron RF-8
description: Hyperthermia for 40 minutes, with maximum temperature setted on 42℃ ± 0.5℃ as upper limit, twice a week for a total of 10 times.
arm group label: HT+ACT
arm group label: HT+ACT+CT
arm group label: HT+ACT+PD-1
arm group label: HT+CT
intervention type: Biological
intervention name: Adoptive cellular Immunotherapy
description: Mononuclear cells were collected from 50ml peripheral blood , and cultured cytokine-induced killer cells for 15-20 days. Cells were infused back to the patients in 3 times via intravenous infusion .Patients will received at least 2 cycles of CIK Immunotherapy . If the evaluation of the treatment is complete response, partial response or stable disease, additional cycles were eligible.
arm group label: HT+ACT
arm group label: HT+ACT+CT
arm group label: HT+ACT+PD-1
intervention type: Drug
intervention name: Anti-PD-1 antibody
description: Patients will receive pembrolizumab 100mg every three weeks and assess the clinical outcome every 2 dosage of anti-PD-1 antibody treatment.
arm group label: HT+ACT+PD-1
intervention type: Drug
intervention name: Chemotherapy
description: Patients will receive standard chemotherapy until disease progression, unacceptable toxicity or patient refusal.
arm group label: HT+ACT+CT
arm group label: HT+CT
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jun Ren, MD,PhD
phone: 86-10-63926317
email: renjun9688@yahoo.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Capital Medical University
investigator full name: Jun Ren MD, PhD
investigator title: Director,Capital Medical University (CMU)Cancer Center
mesh term: Neoplasm Metastasis
mesh term: Neoplasms, Second Primary
mesh term: Pelvic Neoplasms
mesh term: Hyperthermia
mesh term: Antibodies
sharing ipd: Undecided