<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/NCT03791905</url>
  </required_header>
  <id_info>
    <org_study_id>PETESCC</org_study_id>
    <nct_id>NCT03791905</nct_id>
  </id_info>
  <brief_title>PET Imaging-guided Chemoradiotherapy in Esophageal Squamous Cell Carcinoma</brief_title>
  <official_title>A Phase II Randomized Trial of PET Imaging in Assessing Response to Induction Chemotherapy in Esophageal Squamous Cell Carcinoma Treated With Definitive Chemoradiotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mian XI</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sun Yat-sen University</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>
      Since multiple studies have demonstrated that PET can identify responders and non-responders&#xD;
      to induction chemotherapy, using FDG-PET imaging to guide treatment decisions has prompted&#xD;
      interest in clinical practice. The aim of this study was to evaluate whether changing&#xD;
      chemotherapy regimen during radiation based on PET response to induction chemotherapy can&#xD;
      improve clinical complete response (cCR) in patients with unresectable esophageal squamous&#xD;
      cell carcinoma (ESCC).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A total of 216 patients with baseline PET scan were randomized to one of 2 induction&#xD;
      chemotherapy arms: paclitaxel/cisplatin (TP) on days 1, 22 or FOLFOX (oxaliplatin,&#xD;
      leucovorin, 5-FU) on days 1, 15, 29. Repeat PET was performed on days 36-42 and changes in&#xD;
      max standardized uptake value (SUVmax) from baseline were assessed. Using a predefined&#xD;
      cut-off value of a 35% decrease in SUVmax, PET responders (≥35% decrease in SUVmax) continued&#xD;
      on the same chemotherapy regimen during radiotherapy, whereas PET non-responders (&lt;35%&#xD;
      decrease in SUVmax) crossed over to an alternative chemotherapy regimen concomitantly with&#xD;
      radiation. All patients received external-beam radiation using intensity-modulated&#xD;
      radiotherapy. The prescribed dose is generally 50-60 Gy in 25-28 fractions, 5 days per week.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 15, 2019</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">July 2021</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>
    <intervention_model_description>Randomized parallel study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>clinical complete response</measure>
    <time_frame>3 months after the treatment (plus or minus 7 days)</time_frame>
    <description>RECIST (Response Evaluation Criteria in Solid Tumors) criteria was used to determine the tumor response. Tumor response was evaluated 3 months after the completion of treatment based on CT or PET-CT scans, endoscopy with biopsies.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>3 years after randomization</time_frame>
    <description>From the enrollment to the date of death from any cause or date of lost follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>3 years after randomization</time_frame>
    <description>From the date of randomization to the date of disease progression or last follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chemoradiotherapy-related toxicity</measure>
    <time_frame>From the date of randomization to the 3 months after treatment</time_frame>
    <description>Treatment-related toxicity</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">216</enrollment>
  <condition>Neoplasm, Esophageal</condition>
  <condition>Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>TP Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with baseline PET scan assigned to this Arm will receive two cycles of 3-weekly schedule of induction chemotherapy with paclitaxel/cisplatin (TP), consisting of paclitaxel 150 mg/m2 on day 1 and cisplatin 75 mg/m2 on day 1. Repeat PET was performed on days 36-42 and changes in SUVmax from baseline were assessed. PET responders (≥35% decrease in SUVmax) continued on the same chemotherapy regimen during radiotherapy, whereas PET non-responders (&lt;35% decrease in SUVmax) crossed over to FOLFOX regimen concomitantly with radiation. All patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is generally 50-60 Gy in 25-28 fractions.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>FOLFOX Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with baseline PET scan assigned to this Arm will receive three cycles of 2-weekly schedule of induction chemotherapy with FOLFOX (oxaliplatin, leucovorin, 5-FU), consisting of oxaliplatin 85 mg/m2 on day 1, leucovorin 400 mg/m2, and 5-FU 2 g/m2 on day 1. Repeat PET was performed on days 36-42 and changes in SUVmax from baseline were assessed. PET responders (≥35% decrease in SUVmax) continued on the same chemotherapy regimen during radiotherapy, whereas PET non-responders (&lt;35% decrease in SUVmax) crossed over to TP regimen concomitantly with radiation. All patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is generally 50-60 Gy in 25-28 fractions.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>chemotherapy drug</description>
    <arm_group_label>TP Arm</arm_group_label>
    <other_name>Taxol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>chemotherapy drug</description>
    <arm_group_label>TP Arm</arm_group_label>
    <other_name>DDP</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>chemotherapy drug</description>
    <arm_group_label>FOLFOX Arm</arm_group_label>
    <other_name>OXA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5-FU</intervention_name>
    <description>chemotherapy drug</description>
    <arm_group_label>FOLFOX Arm</arm_group_label>
    <other_name>Fluorouracil</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leucovorin</intervention_name>
    <description>chemotherapy drug</description>
    <arm_group_label>FOLFOX Arm</arm_group_label>
    <other_name>CF</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Intensity-modulated radiotherapy</intervention_name>
    <description>radiotherapy technique</description>
    <arm_group_label>FOLFOX Arm</arm_group_label>
    <arm_group_label>TP Arm</arm_group_label>
    <other_name>IMRT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>PET</intervention_name>
    <description>Using PET to evaluate response to induction chemotherapy</description>
    <arm_group_label>FOLFOX Arm</arm_group_label>
    <arm_group_label>TP Arm</arm_group_label>
    <other_name>PET-CT</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed squamous cell carcinoma of the esophagus;&#xD;
&#xD;
          2. Absence of hematogenous metastasis disease, confirmed by endoscopic ultrasound (EUS)&#xD;
             and PET-CT scan (according to UICC TNM version 8);&#xD;
&#xD;
          3. Not suitable for surgery (either for medical reasons or patient's choice);&#xD;
&#xD;
          4. Age at diagnosis 18 to 70 years;&#xD;
&#xD;
          5. Eastern Cooperative Oncology Group performance status ≤ 2&#xD;
&#xD;
          6. No prior cancer therapy;&#xD;
&#xD;
          7. No history of concomitant or previous malignancy;&#xD;
&#xD;
          8. Hematologic function: WBC ≥ 4.0×109/L, PLT ≥ 80×109/L, Hb ≥ 10mg/dL;&#xD;
&#xD;
          9. Renal function: Cr ≤ 1.25×UNL;&#xD;
&#xD;
         10. Hepatic function: BIL ≤ 1.5×UNL, ALT/AST ≤ 2.5×UNL;&#xD;
&#xD;
         11. Documented informed consent to participate in the trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Younger than 18 or older than 70 years of age;&#xD;
&#xD;
          2. ECOG performance status of 3 or above;&#xD;
&#xD;
          3. Other cancer history;&#xD;
&#xD;
          4. Previous radiotherapy history;&#xD;
&#xD;
          5. Subjects with distant metastases;&#xD;
&#xD;
          6. Pregnancy or breast feeding. Women of childbearing age must use effective&#xD;
             contraception;&#xD;
&#xD;
          7. Serious cardiovascular disease (congestive heart failure, uncontrollable arrhythmia,&#xD;
             unstable angina, myocardial infarction, serious heart valve disease, resistant&#xD;
             hypertension);&#xD;
&#xD;
          8. Evidence of bleeding diathesis or serious infection.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mian XI, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Sun Yat-sen University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Mian XI, MD</last_name>
    <phone>+86-20-87343385</phone>
    <email>ximian@sysucc.org.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Mengzhong Liu, MD</last_name>
    <phone>+86-20-87343385</phone>
    <email>liumzh@sysucc.org.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Sun Yat-sen University Cancer Center</name>
      <address>
        <city>Guanzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mian Xi, MD</last_name>
      <phone>+86-20-87343385</phone>
      <email>ximian@sysucc.org.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <results_reference>
    <citation>Ku GY, Kriplani A, Janjigian YY, Kelsen DP, Rusch VW, Bains M, Chou J, Capanu M, Wu AJ, Goodman KA, Ilson DH. Change in chemotherapy during concurrent radiation followed by surgery after a suboptimal positron emission tomography response to induction chemotherapy improves outcomes for locally advanced esophageal adenocarcinoma. Cancer. 2016 Jul 1;122(13):2083-90. doi: 10.1002/cncr.30028. Epub 2016 May 6.</citation>
    <PMID>27152857</PMID>
  </results_reference>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>December 31, 2018</study_first_submitted>
  <study_first_submitted_qc>December 31, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">January 3, 2019</study_first_posted>
  <last_update_submitted>March 21, 2021</last_update_submitted>
  <last_update_submitted_qc>March 21, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 23, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Mian XI</investigator_full_name>
    <investigator_title>Associate Preofessor</investigator_title>
  </responsible_party>
  <keyword>Esophageal squamous cell carcinoma</keyword>
  <keyword>PET</keyword>
  <keyword>Definitive chemoradiotherapy</keyword>
  <keyword>Induction chemotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Esophageal Squamous Cell Carcinoma</mesh_term>
    <mesh_term>Esophageal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leucovorin</mesh_term>
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Oxaliplatin</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/NCT03791905
org study id: PETESCC
nct id: NCT03791905
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Since multiple studies have demonstrated that PET can identify responders and non-responders
      to induction chemotherapy, using FDG-PET imaging to guide treatment decisions has prompted
      interest in clinical practice. The aim of this study was to evaluate whether changing
      chemotherapy regimen during radiation based on PET response to induction chemotherapy can
      improve clinical complete response (cCR) in patients with unresectable esophageal squamous
      cell carcinoma (ESCC).
A total of 216 patients with baseline PET scan were randomized to one of 2 induction
      chemotherapy arms: paclitaxel/cisplatin (TP) on days 1, 22 or FOLFOX (oxaliplatin,
      leucovorin, 5-FU) on days 1, 15, 29. Repeat PET was performed on days 36-42 and changes in
      max standardized uptake value (SUVmax) from baseline were assessed. Using a predefined
      cut-off value of a 35% decrease in SUVmax, PET responders (≥35% decrease in SUVmax) continued
      on the same chemotherapy regimen during radiotherapy, whereas PET non-responders (<35%
      decrease in SUVmax) crossed over to an alternative chemotherapy regimen concomitantly with
      radiation. All patients received external-beam radiation using intensity-modulated
      radiotherapy. The prescribed dose is generally 50-60 Gy in 25-28 fractions, 5 days per week.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized parallel study
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: clinical complete response
time frame: 3 months after the treatment (plus or minus 7 days)
description: RECIST (Response Evaluation Criteria in Solid Tumors) criteria was used to determine the tumor response. Tumor response was evaluated 3 months after the completion of treatment based on CT or PET-CT scans, endoscopy with biopsies.
measure: Overall survival
time frame: 3 years after randomization
description: From the enrollment to the date of death from any cause or date of lost follow-up
measure: Progression-free survival
time frame: 3 years after randomization
description: From the date of randomization to the date of disease progression or last follow-up
measure: Chemoradiotherapy-related toxicity
time frame: From the date of randomization to the 3 months after treatment
description: Treatment-related toxicity
arm group label: TP Arm
arm group type: Experimental
description: Patients with baseline PET scan assigned to this Arm will receive two cycles of 3-weekly schedule of induction chemotherapy with paclitaxel/cisplatin (TP), consisting of paclitaxel 150 mg/m2 on day 1 and cisplatin 75 mg/m2 on day 1. Repeat PET was performed on days 36-42 and changes in SUVmax from baseline were assessed. PET responders (≥35% decrease in SUVmax) continued on the same chemotherapy regimen during radiotherapy, whereas PET non-responders (<35% decrease in SUVmax) crossed over to FOLFOX regimen concomitantly with radiation. All patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is generally 50-60 Gy in 25-28 fractions.
arm group label: FOLFOX Arm
arm group type: Experimental
description: Patients with baseline PET scan assigned to this Arm will receive three cycles of 2-weekly schedule of induction chemotherapy with FOLFOX (oxaliplatin, leucovorin, 5-FU), consisting of oxaliplatin 85 mg/m2 on day 1, leucovorin 400 mg/m2, and 5-FU 2 g/m2 on day 1. Repeat PET was performed on days 36-42 and changes in SUVmax from baseline were assessed. PET responders (≥35% decrease in SUVmax) continued on the same chemotherapy regimen during radiotherapy, whereas PET non-responders (<35% decrease in SUVmax) crossed over to TP regimen concomitantly with radiation. All patients received external-beam radiation using intensity-modulated radiotherapy. The prescribed dose is generally 50-60 Gy in 25-28 fractions.
intervention type: Drug
intervention name: Paclitaxel
description: chemotherapy drug
arm group label: TP Arm
other name: Taxol
intervention type: Drug
intervention name: Cisplatin
description: chemotherapy drug
arm group label: TP Arm
other name: DDP
intervention type: Drug
intervention name: Oxaliplatin
description: chemotherapy drug
arm group label: FOLFOX Arm
other name: OXA
intervention type: Drug
intervention name: 5-FU
description: chemotherapy drug
arm group label: FOLFOX Arm
other name: Fluorouracil
intervention type: Drug
intervention name: Leucovorin
description: chemotherapy drug
arm group label: FOLFOX Arm
other name: CF
intervention type: Radiation
intervention name: Intensity-modulated radiotherapy
description: radiotherapy technique
arm group label: FOLFOX Arm
arm group label: TP Arm
other name: IMRT
intervention type: Device
intervention name: PET
description: Using PET to evaluate response to induction chemotherapy
arm group label: FOLFOX Arm
arm group label: TP Arm
other name: PET-CT
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Mian XI, MD
role: Study Chair
affiliation: Sun Yat-sen University
last name: Mian XI, MD
phone: +86-20-87343385
email: ximian@sysucc.org.cn
last name: Mengzhong Liu, MD
phone: +86-20-87343385
email: liumzh@sysucc.org.cn
facility: 
status: Recruiting
contact: 
country: China
citation: Ku GY, Kriplani A, Janjigian YY, Kelsen DP, Rusch VW, Bains M, Chou J, Capanu M, Wu AJ, Goodman KA, Ilson DH. Change in chemotherapy during concurrent radiation followed by surgery after a suboptimal positron emission tomography response to induction chemotherapy improves outcomes for locally advanced esophageal adenocarcinoma. Cancer. 2016 Jul 1;122(13):2083-90. doi: 10.1002/cncr.30028. Epub 2016 May 6.
PMID: 27152857
responsible party type: Sponsor-Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Mian XI
investigator title: Associate Preofessor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Esophageal Squamous Cell Carcinoma
mesh term: Esophageal Neoplasms
mesh term: Leucovorin
mesh term: Paclitaxel
mesh term: Fluorouracil
mesh term: Oxaliplatin
sharing ipd: No