<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/NCT03288350</url>
  </required_header>
  <id_info>
    <org_study_id>MS100070_0073</org_study_id>
    <nct_id>NCT03288350</nct_id>
  </id_info>
  <brief_title>mDCF + Avelumab in Resectable Esophago-gastric Adenocarcinoma (EGA)</brief_title>
  <official_title>Phase II Trial of Perioperative PD-L1 Inhibition With Avelumab and Docetaxel, Cisplatin and 5-Fluorouracil for Resectable Locally Advanced Esophago-Gastric Adenocarcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>McGill University Health Centre/Research Institute of the McGill University Health Centre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>McGill University Health Centre/Research Institute of the McGill University Health Centre</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single-center, single-arm, open-label, Simon 2-stage, phase II trial in up to 55&#xD;
      patients with a potentially resectable, histologically-proven, adenocarcinoma or poorly&#xD;
      differentiated carcinoma of the stomach, esophagogastric junction (EGJ), or lower third of&#xD;
      the esophagus.&#xD;
&#xD;
      Patients will receive neoadjuvant therapy consisting of 4 cycles of avelumab added to the&#xD;
      modified chemotherapy regimen of docetaxel, cisplatin, 5- fluorouracil. Following surgery,&#xD;
      pathologic response will be assessed. Patients will then receive adjuvant therapy consisting&#xD;
      of 4 cycles of mDCF + avelumab. Patients will be followed to assess two-year disease-free&#xD;
      survival rates.&#xD;
&#xD;
      The primary objective of this study is to assess the effect on pathologic complete response&#xD;
      rate (pCR) of adding avelumab to an mDCF regimen. The secondary objectives of this study are&#xD;
      to determine the safety of adding avelumab to an mDCF regimen and assess its effect on&#xD;
      two-year disease-free survival.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 22, 2018</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2020</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>Pathologic Complete Response (pCR)</measure>
    <time_frame>30±4 weeks</time_frame>
    <description>Assessment of the pathologic complete response (pCR) rate after preoperative (neoadjuvant) treatment. pCR has been shown to correlate with long-term outcomes.For the purpose of this study, pCR is considered to represent grade 0 and grade 1 responses, defined by the criteria of the College of American Pathologists.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Two-Year Disease Free Survival (DFS)</measure>
    <time_frame>104 weeks</time_frame>
    <description>Analysis of two-year disease-free survival (DFS) following treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety Assessment of Adding Avelumab to mDCF</measure>
    <time_frame>104 weeks</time_frame>
    <description>Measurement of the incidence of grade 3 or 4 avelumab-related adverse events following treatment.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">55</enrollment>
  <condition>Gastric Adenocarcinoma</condition>
  <condition>Esophageal Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>mDCF + Avelumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive neoadjuvant therapy consisting of 4 cycles of avelumab added to the modified chemotherapy regimen of docetaxel, cisplatin, 5-fluorouracil, followed by surgery and assessment of pathologic response. Then they will receive 4 cycles of adjuvant therapy of docetaxel, cisplatin, 5-fluorouracil and avelumab.&#xD;
Docetaxel as a one-hour 40 mg/m2 IV infusion on day 1. Cisplatin 40 mg/m2 IV infusion on day 1. 5-FU 1000 mg/m2/day over 2 days. Avelumab 10 mg/kg following the completion of the mDCF regimen.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>mDCF + Avelumab</intervention_name>
    <description>Patients will receive neoadjuvant therapy consisting of 4 cycles of avelumab added to the modified chemotherapy regimen of docetaxel, cisplatin, 5-fluorouracil (mDCF), followed by surgery and assessment of pathologic response. Then they will receive 4 cycles of adjuvant therapy of mDCF and avelumab.</description>
    <arm_group_label>mDCF + Avelumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed, informed consent;&#xD;
&#xD;
          2. Age 18 years or older;&#xD;
&#xD;
          3. Histological diagnosis of adenocarcinoma or poorly differentiated carcinoma of the&#xD;
             stomach, esophagogastric junction (EGJ), or lower third of the esophagus;&#xD;
&#xD;
          4. The tumour must be deemed by the team to be potentially resectable. This includes&#xD;
             imaging studies (detailed below) to clinically stage the tumor and rule out the&#xD;
             presence of metastatic disease, and includes a preoperative laparoscopic evaluation&#xD;
             for gastric tumors only;&#xD;
&#xD;
          5. Stage IB (TlNl only), II, IHA, IIIB;&#xD;
&#xD;
          6. Life expectancy greater than 3 months;&#xD;
&#xD;
          7. ECOG performance status of 0-1;&#xD;
&#xD;
          8. Neutrophils ~ 1500/μL;&#xD;
&#xD;
          9. Platelet count~ 100,000/μL;&#xD;
&#xD;
         10. Hemoglobin~ 9 g/dL;&#xD;
&#xD;
         11. Total bilirubin level :S 1.5 x the upper limit of normal (ULN) range unless consistent&#xD;
             with Gilbert's syndrome (normal direct bilirubin);&#xD;
&#xD;
         12. AST and ALT :S 2.5 x ULN;&#xD;
&#xD;
         13. If serum creatinine above upper limit of normal (ULN), creatinine clearance ~ 60&#xD;
             ml/min as determined by 24-h creatinine clearance or Cockcroft-Gault formula;&#xD;
&#xD;
         14. Negative pregnancy test for women of child-bearing potential; and&#xD;
&#xD;
         15. Highly effective contraception for both male and female subjects throughout the study&#xD;
             and for at least 60 days after last avelumab treatment administration if the risk of&#xD;
             conception exists.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Current or prior use of immunosuppressive medication, including corticosteroids,&#xD;
             within 7 days prior to registration EXCEPT for the following:&#xD;
&#xD;
               1. intranasal, intra-ocular, inhaled, topical steroids, or local steroid injection&#xD;
                  (e.g., intraarticular injection);&#xD;
&#xD;
               2. Systemic corticosteroids at physiologic doses :S 10 mg/day of prednisone or&#xD;
                  equivalent;&#xD;
&#xD;
               3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan&#xD;
                  premedication);&#xD;
&#xD;
          2. Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory&#xD;
             agent. However, patients with diabetes type I, vitiligo, psoriasis, hypo- or&#xD;
             hyperthyroid disease not requiring immunosuppressive treatment are eligible;&#xD;
&#xD;
          3. Prior organ transplantation, including allogeneic stem cell transplantation;&#xD;
&#xD;
          4. Squamous-cell carcinoma diagnosis;&#xD;
&#xD;
          5. Significant acute or chronic active infections requiring systemic therapy, including,&#xD;
             among others:&#xD;
&#xD;
               1. Known history of testing positive test for human immunodeficiency virus (HIV) or&#xD;
                  known acquired immunodeficiency syndrome (AIDS);&#xD;
&#xD;
               2. Positive test for HBV surface antigen and I or confirmatory HCV RNA (if anti-HCV&#xD;
                  antibody tested positive);&#xD;
&#xD;
          6. Vaccination with live vaccines within 4 weeks of the first dose of avelumab and while&#xD;
             on trial;&#xD;
&#xD;
          7. Known severe hypersensitivity reactions to monoclonal antibodies (Grade 2: 3 NCI CTCAE&#xD;
             v 4.03) or to any component in avelumab's formulation, any history of anaphylaxis, or&#xD;
             uncontrolled asthma (that is, 3 or more features of partially controlled asthma);&#xD;
&#xD;
          8. Known severe hypersensitivity reaction to cisplatin, docetaxel, 5-FU or drugs&#xD;
             formulated with polysorbate;&#xD;
&#xD;
          9. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular&#xD;
             accident/stroke (&lt; 6 months prior to enrollment), myocardial infarction(&lt; 6 months&#xD;
             prior to enrollment), unstable angina, congestive heart failure (2: New York Heart&#xD;
             Association Classification Class II), or serious cardiac arrhythmia requiring&#xD;
             medication;&#xD;
&#xD;
         10. Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade&gt; 1 ); however,&#xD;
             alopecia, sensory neuropathy Grade :S 2, or other Grade :S 2 not constituting a safety&#xD;
             risk based on investigator's judgment are acceptable;&#xD;
&#xD;
         11. Other severe acute or chronic medical conditions including colitis, inflammatory bowel&#xD;
             disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent&#xD;
             (within the past year) or active suicidal ideation or behavior; or laboratory&#xD;
             abnormalities that may increase the risk associated with study participation or study&#xD;
             treatment administration or may interfere with the interpretation of study results&#xD;
             and, in the judgment of the investigator, would make the patient inappropriate for&#xD;
             entry into this study;&#xD;
&#xD;
         12. Known alcohol or drug abuse;&#xD;
&#xD;
         13. Prior systemic therapy for gastric cancer;&#xD;
&#xD;
         14. Prior exposure to antibodies directed at PD-1, PD-L 1, CTLA 4 antigens;&#xD;
&#xD;
         15. Pre-existing medical conditions precluding treatment, including any contraindication&#xD;
             for major surgery;&#xD;
&#xD;
         16. Pregnancy or lactating mothers. Women of childbearing age must use contraception&#xD;
             during and for 3 months following treatment;&#xD;
&#xD;
         17. ECOG performance status of 2 or higher;&#xD;
&#xD;
         18. Significant hearing impairment, as judged by the need for or use of a hearing aid. If&#xD;
             there is any uncertainty regarding the degree of hearing impairment, an audiogram will&#xD;
             be done. If the audiogram is grossly normal or shows only minor hearing impairment&#xD;
             (i.e. not requiring hearing aid), the patient may be enrolled;&#xD;
&#xD;
         19. Unwillingness to undergo investigations and/or treatment as outlined on the study; or&#xD;
&#xD;
         20. Participation to another trial where an investigational drug is being used.&#xD;
&#xD;
         21. History of another malignancy requiring treatment within the last 3 years. Exceptions&#xD;
             include basal cell carcinoma of the skin, squamous cell carcinoma of the skin treated&#xD;
             curatively and in-situ cervical cancer.&#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_official>
    <last_name>Thierry Alcindor, MD, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Associate Director, Oncology Clinical Trials</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Touhid Opu, MBBS, MSc</last_name>
    <phone>514-934-1934</phone>
    <phone_ext>34573</phone_ext>
    <email>touhid.opu@mail.mcgill.ca</email>
  </overall_contact>
  <location>
    <facility>
      <name>McGill University Health Centre</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H4A 3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Penny Chipman</last_name>
      <phone>514-934-1934</phone>
      <phone_ext>64802</phone_ext>
      <email>penny.chipman@muhc.mcgill.ca</email>
    </contact>
    <investigator>
      <last_name>Thierry Alcindor, MD, MSc</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>September 15, 2017</study_first_submitted>
  <study_first_submitted_qc>September 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 20, 2017</study_first_posted>
  <last_update_submitted>March 20, 2018</last_update_submitted>
  <last_update_submitted_qc>March 20, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 22, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>McGill University Health Centre/Research Institute of the McGill University Health Centre</investigator_affiliation>
    <investigator_full_name>Thierry Alcindor</investigator_full_name>
    <investigator_title>Associate Director, Oncology Clinical Trials</investigator_title>
  </responsible_party>
  <keyword>Phase II Trial</keyword>
  <keyword>Esophago-Gastric Adenocarcinoma</keyword>
  <keyword>Avelumab</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Avelumab</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/NCT03288350
org study id: MS100070_0073
nct id: NCT03288350
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a single-center, single-arm, open-label, Simon 2-stage, phase II trial in up to 55
      patients with a potentially resectable, histologically-proven, adenocarcinoma or poorly
      differentiated carcinoma of the stomach, esophagogastric junction (EGJ), or lower third of
      the esophagus.

      Patients will receive neoadjuvant therapy consisting of 4 cycles of avelumab added to the
      modified chemotherapy regimen of docetaxel, cisplatin, 5- fluorouracil. Following surgery,
      pathologic response will be assessed. Patients will then receive adjuvant therapy consisting
      of 4 cycles of mDCF + avelumab. Patients will be followed to assess two-year disease-free
      survival rates.

      The primary objective of this study is to assess the effect on pathologic complete response
      rate (pCR) of adding avelumab to an mDCF regimen. The secondary objectives of this study are
      to determine the safety of adding avelumab to an mDCF regimen and assess its effect on
      two-year disease-free survival.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pathologic Complete Response (pCR)
time frame: 30±4 weeks
description: Assessment of the pathologic complete response (pCR) rate after preoperative (neoadjuvant) treatment. pCR has been shown to correlate with long-term outcomes.For the purpose of this study, pCR is considered to represent grade 0 and grade 1 responses, defined by the criteria of the College of American Pathologists.
measure: Two-Year Disease Free Survival (DFS)
time frame: 104 weeks
description: Analysis of two-year disease-free survival (DFS) following treatment.
measure: Safety Assessment of Adding Avelumab to mDCF
time frame: 104 weeks
description: Measurement of the incidence of grade 3 or 4 avelumab-related adverse events following treatment.
arm group label: mDCF + Avelumab
arm group type: Experimental
description: Patients will receive neoadjuvant therapy consisting of 4 cycles of avelumab added to the modified chemotherapy regimen of docetaxel, cisplatin, 5-fluorouracil, followed by surgery and assessment of pathologic response. Then they will receive 4 cycles of adjuvant therapy of docetaxel, cisplatin, 5-fluorouracil and avelumab.
Docetaxel as a one-hour 40 mg/m2 IV infusion on day 1. Cisplatin 40 mg/m2 IV infusion on day 1. 5-FU 1000 mg/m2/day over 2 days. Avelumab 10 mg/kg following the completion of the mDCF regimen.
intervention type: Drug
intervention name: mDCF + Avelumab
description: Patients will receive neoadjuvant therapy consisting of 4 cycles of avelumab added to the modified chemotherapy regimen of docetaxel, cisplatin, 5-fluorouracil (mDCF), followed by surgery and assessment of pathologic response. Then they will receive 4 cycles of adjuvant therapy of mDCF and avelumab.
arm group label: mDCF + Avelumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Thierry Alcindor, MD, MSc
role: Principal Investigator
affiliation: Associate Director, Oncology Clinical Trials
last name: Touhid Opu, MBBS, MSc
phone: 514-934-1934
phone ext: 34573
email: touhid.opu@mail.mcgill.ca
facility: 
status: Recruiting
contact: 
investigator: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
investigator full name: Thierry Alcindor
investigator title: Associate Director, Oncology Clinical Trials
mesh term: Adenocarcinoma
mesh term: Avelumab
sharing ipd: No