<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/NCT02217020</url>
  </required_header>
  <id_info>
    <org_study_id>GIHSYSU07</org_study_id>
    <nct_id>NCT02217020</nct_id>
  </id_info>
  <brief_title>Neoadjuvant FOLFOXIRI Chemotherapy Alone for Locally Advanced Rectal Cancer</brief_title>
  <acronym>FORTUNE</acronym>
  <official_title>A Phase II Study of Neoadjuvant FOLFOXIRI Chemotherapy Alone in Treating Patients With Locally Advanced Rectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sun Yat-sen University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The standard treatment for stage 2/3 rectal cancer is neoadjuvant 5-Fu based chemoradiation.&#xD;
      However, preoperative radiation cause kinds of adverse events, some were irreversible. And&#xD;
      the survival benefit was not obvious. Whether chemotherapy alone is effective enough in&#xD;
      treating rectal cancer is not yet known. Here, the investigators chose all the three active&#xD;
      cytotoxic agents (5-FU, Oxaliplatin, Irinotecan) as the neoadjuvant treatment regimen&#xD;
      (FOLFOXIRI). The purpose of the study is to evaluate the efficacy of FOLFOXIRI as neoadjuvant&#xD;
      regimen in treating patients with locally advanced rectal cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Preoperative chemoradiotherapy could improve the local control of locally advanced rectal&#xD;
      cancer, but the role was limited, only 5%. The adverse event cause by radiotherapy was&#xD;
      severe. This single phase II trial was aimed to evaluate the efficacy of triplet regimen&#xD;
      (FOLFOXIRI) in treating patients with locally advanced rectal cancer. All patients will&#xD;
      receive the study regimen every 2 weeks for 4-6 cycles. MRI of the pelvic will be performed&#xD;
      after 4 cycles of chemotherapy to assess clinical response. If the tumor response over 20%&#xD;
      after 4 cycles of treatment, the patient will go to surgery (TME) directly or 2 more cycles&#xD;
      of treatment before surgery under the decision of MDT. On the contrary, if the tumor show&#xD;
      poor response (&lt;20%), radiotherapy will be performed before operation. After surgery, 6-8&#xD;
      cycles of mFOLFOX6 will be given as adjuvant chemotherapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 15, 2014</start_date>
  <completion_date type="Actual">August 15, 2017</completion_date>
  <primary_completion_date type="Actual">September 15, 2016</primary_completion_date>
  <phase>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>The ratio of tumor downstaging to stage 0 and stage I</measure>
    <time_frame>2 year</time_frame>
    <description>Tumor downstaging from stage II or III to pathologic complete response (stage 0) and stage I</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Average neoadjuvant rectal cancer score</measure>
    <time_frame>2 year</time_frame>
    <description>neoadjuvant rectal cancer score (NAR) =[5*pN-3*(cT-pT)+12]^2/9.61 had been proposed and proven to be the surrogate endpoint of overall survival. It refered to the predictive value of lymphnode status and primary tumor downstaging on Overall survival of rectal cancer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the local Recurrence rate</measure>
    <time_frame>3 year</time_frame>
    <description>the ratio of patients with local recurrence within 3 years</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recurrence free survival</measure>
    <time_frame>3 years</time_frame>
    <description>3 years recurrence free survival of this group of patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reported Adverse events</measure>
    <time_frame>2 years</time_frame>
    <description>Number of patients with adverse events and severity according to NCI CTC 4.0 after treatment with this regimen.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Rectal Cancer</condition>
  <arm_group>
    <arm_group_label>FOLFOXIRI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>patients received FOLFOXIRI alone for 4 cycles before surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FOLFOXIRI</intervention_name>
    <description>irinotecan* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle</description>
    <arm_group_label>FOLFOXIRI</arm_group_label>
    <other_name>5-FU</other_name>
    <other_name>Oxaliplatin</other_name>
    <other_name>Irinotecan</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Diagnosis of adenocarcinoma of the rectum&#xD;
&#xD;
          -  Age: 18-70 years old&#xD;
&#xD;
          -  Signed informed consent; able to comply with study and/or follow- up procedures&#xD;
&#xD;
          -  Stage of the primary tumor may be determined by ultrasound or MRI&#xD;
&#xD;
          -  Stage II (T3-4, N0 [N0 is defined as all imaged lymph nodes &lt; 1.0 cm]) OR stage III&#xD;
             (T1-4, N1-2 [with the definition of a clinically positive lymph node being any node ≥&#xD;
             1.0 cm]&#xD;
&#xD;
          -  Tumor palpable by digital rectal exam OR accessible by proctoscope or sigmoidoscope&#xD;
&#xD;
          -  Distal border of the tumor must be located &lt; 12 cm from the anal verge&#xD;
&#xD;
          -  Tumor amenable to curative resection&#xD;
&#xD;
          -  Adequate bone marrow, hepatic and renal function as assessed by the following&#xD;
             laboratory requirements conducted within 7 days of starting study treatment:&#xD;
&#xD;
          -  Leukocytes ≥ 3.0 x109/ L, absolute neutrophil count (ANC) ≥ 1.5 x109/ L, platelet&#xD;
             count ≥ 100 x109/ L, hemoglobin (Hb) ≥ 9g/ dL.&#xD;
&#xD;
          -  Total bilirubin ≤1.5 x the upper limit of normal (ULN).&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN.&#xD;
&#xD;
          -  Alkaline phosphatase limit ≤ 5x ULN.&#xD;
&#xD;
          -  Amylase and lipase ≤ 1.5 x the ULN.&#xD;
&#xD;
          -  Serum creatinine ≤ 1.5 x the ULN.&#xD;
&#xD;
          -  Calculated creatinine clearance or 24 hour creatinine clearance ≥ 50 mL/ min.&#xD;
&#xD;
          -  No renal disease that would preclude study treatment or follow-up&#xD;
&#xD;
          -  ECOG status: 0～1&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hypersensitivity to fluorouracil, oxaliplatin or irinotecan.&#xD;
&#xD;
          -  No More than 4 weeks since prior participation in any investigational drug study&#xD;
&#xD;
          -  More than 4 weeks since prior participation in any investigational drug study&#xD;
&#xD;
          -  Clear indication of involvement of the pelvic side walls by imaging&#xD;
&#xD;
          -  With distant metastasis&#xD;
&#xD;
          -  History of invasive rectal malignancy, regardless of disease-free interval&#xD;
&#xD;
          -  Fertile patients must use effective contraception&#xD;
&#xD;
          -  Uncontrolled hypertension&#xD;
&#xD;
          -  Cardiovascular disease that would preclude study treatment or follow-up&#xD;
&#xD;
          -  Lack of upper gastrointestinal tract integrity or malabsorption syndrome，active upper&#xD;
             gastrointestinal tract bleeding&#xD;
&#xD;
          -  Synchronous colon cancer&#xD;
&#xD;
          -  Pregnant or nursing, Fertile patients do not use effective contraception&#xD;
&#xD;
          -  Other malignancy within the past 5 years except effectively treated squamous cell or&#xD;
             basal cell skin cancer, melanoma in situ, carcinoma in situ of the cervix, or&#xD;
             carcinoma in situ of the colon or rectum&#xD;
&#xD;
          -  No psychiatric or addictive disorders, or other conditions that, in the opinion of the&#xD;
             investigator, would preclude study participation&#xD;
&#xD;
          -  patients refused to signed informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Gastrointestinal Hospital, Sun Yatsen University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510655</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>August 10, 2014</study_first_submitted>
  <study_first_submitted_qc>August 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 15, 2014</study_first_posted>
  <last_update_submitted>April 10, 2021</last_update_submitted>
  <last_update_submitted_qc>April 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Yanhong Deng</investigator_full_name>
    <investigator_title>Doctor</investigator_title>
  </responsible_party>
  <keyword>Rectal Cancer</keyword>
  <keyword>Locally advanced rectal cancer</keyword>
  <keyword>Neoadjuvant</keyword>
  <keyword>chemotherapy</keyword>
  <keyword>FOLFOXIRI</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Oxaliplatin</mesh_term>
    <mesh_term>Irinotecan</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/NCT02217020
org study id: GIHSYSU07
nct id: NCT02217020
lead sponsor: 
has dmc: No
The standard treatment for stage 2/3 rectal cancer is neoadjuvant 5-Fu based chemoradiation.
      However, preoperative radiation cause kinds of adverse events, some were irreversible. And
      the survival benefit was not obvious. Whether chemotherapy alone is effective enough in
      treating rectal cancer is not yet known. Here, the investigators chose all the three active
      cytotoxic agents (5-FU, Oxaliplatin, Irinotecan) as the neoadjuvant treatment regimen
      (FOLFOXIRI). The purpose of the study is to evaluate the efficacy of FOLFOXIRI as neoadjuvant
      regimen in treating patients with locally advanced rectal cancer.
Preoperative chemoradiotherapy could improve the local control of locally advanced rectal
      cancer, but the role was limited, only 5%. The adverse event cause by radiotherapy was
      severe. This single phase II trial was aimed to evaluate the efficacy of triplet regimen
      (FOLFOXIRI) in treating patients with locally advanced rectal cancer. All patients will
      receive the study regimen every 2 weeks for 4-6 cycles. MRI of the pelvic will be performed
      after 4 cycles of chemotherapy to assess clinical response. If the tumor response over 20%
      after 4 cycles of treatment, the patient will go to surgery (TME) directly or 2 more cycles
      of treatment before surgery under the decision of MDT. On the contrary, if the tumor show
      poor response (<20%), radiotherapy will be performed before operation. After surgery, 6-8
      cycles of mFOLFOX6 will be given as adjuvant chemotherapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The ratio of tumor downstaging to stage 0 and stage I
time frame: 2 year
description: Tumor downstaging from stage II or III to pathologic complete response (stage 0) and stage I
measure: Average neoadjuvant rectal cancer score
time frame: 2 year
description: neoadjuvant rectal cancer score (NAR) =[5*pN-3*(cT-pT)+12]^2/9.61 had been proposed and proven to be the surrogate endpoint of overall survival. It refered to the predictive value of lymphnode status and primary tumor downstaging on Overall survival of rectal cancer.
measure: the local Recurrence rate
time frame: 3 year
description: the ratio of patients with local recurrence within 3 years
measure: Recurrence free survival
time frame: 3 years
description: 3 years recurrence free survival of this group of patients
measure: Reported Adverse events
time frame: 2 years
description: Number of patients with adverse events and severity according to NCI CTC 4.0 after treatment with this regimen.
arm group label: FOLFOXIRI
arm group type: Experimental
description: patients received FOLFOXIRI alone for 4 cycles before surgery.
intervention type: Drug
intervention name: FOLFOXIRI
description: irinotecan* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle
arm group label: FOLFOXIRI
other name: 5-FU
other name: Oxaliplatin
other name: Irinotecan
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Yanhong Deng
investigator title: Doctor
mesh term: Rectal Neoplasms
mesh term: Oxaliplatin
mesh term: Irinotecan