<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/NCT02236936</url>
  </required_header>
  <id_info>
    <org_study_id>AGMT_HNO_PN</org_study_id>
    <nct_id>NCT02236936</nct_id>
  </id_info>
  <brief_title>Parenteral Nutrition for Patients Treated for Locally Advanced Inoperable Tumors of the Head and Neck</brief_title>
  <acronym>AGMT_HNO_PN</acronym>
  <official_title>Randomized Phase III Study: Supplemental Parenteral Nutrition for Patients With Locally Advanced Inoperable Tumors of the Head and Neck, Receiving Definitive Radiotherapy With Cetuximab or Cisplatin</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Arbeitsgemeinschaft medikamentoese Tumortherapie</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Medical University of Graz</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Arbeitsgemeinschaft medikamentoese Tumortherapie</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>
      Prevention of critical weight loss. In patients with Squamous Cell Carcinoma of the Head and&#xD;
      Neck (SCCHN) weight loss is a relevant clinical problem during radiotherapy and might result&#xD;
      in higher treatment related toxicity and discontinuation of a potential curative treatment.&#xD;
      Thus the investigators want to evaluate the efficacy of overnight parenteral nutritional (PN)&#xD;
      support in patients with SCCHN treated with curative radiotherapy (RTX) in combination with&#xD;
      Cetuximab (E) or Cisplatin (P).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators hypothesize that about 60% of patients receiving RTX without supplemental&#xD;
      PN will suffer from critical weight loss of more than 5% during treatment - supplemental&#xD;
      overnight PN might result in significant improvement of the nutritional status .&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study stopped due to low recruitment&#xD;
  </why_stopped>
  <start_date type="Actual">February 3, 2017</start_date>
  <completion_date type="Actual">July 10, 2019</completion_date>
  <primary_completion_date type="Actual">July 10, 2019</primary_completion_date>
  <phase>Phase 3</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Loss of body weight by more than 5% at the end of radiotherapy</measure>
    <time_frame>Difference between baseline and week 8 (after end of RTX)</time_frame>
    <description>Weekly body weight assessments - standardized method for all study sites</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Bioelectrical Impedance Analysis (BIA): reduction of phase angle by &gt; 10% during treatment/observation</measure>
    <time_frame>Prior to and 1 year after start of RTX, within 7 days and 3 months after end of RTX</time_frame>
    <description>Determination of parameters on functional nutritional status: fat-free mass (FFM), total body water (TBW), body fat and phase angle will be evaluated by BIA</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Assessment of physical strength</measure>
    <time_frame>Prior to RTX, weekly during RTX, within 1 week and 3 months after end of RTX</time_frame>
    <description>Handgrip strength measurement, mean value of three consecutive measurements</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of implanted PEG tubes</measure>
    <time_frame>From start of RTX until 3 months after end of RTX</time_frame>
    <description>The number of implanted PEG tubes will be recorded</description>
  </other_outcome>
  <other_outcome>
    <measure>Acute toxicity during radiotherapy</measure>
    <time_frame>During 7 weeks of radiotherapy, at end of radiotherapy and 3 months after radiotherapy</time_frame>
    <description>Acute toxicity according to Common Terminology Criteria for Adverse Events (CTCAE 4.0.)</description>
  </other_outcome>
  <other_outcome>
    <measure>Chronic toxicity after treatment</measure>
    <time_frame>3 months after end of radiotherapy</time_frame>
    <description>Chronic toxicity evaluated according to RTOG (Radiation Therapy Oncology Group)/EORTC (European Organisation for Research and Treatment of Cancer) - Toxicity Criteria</description>
  </other_outcome>
  <other_outcome>
    <measure>Dose and dose intensity of radiotherapy</measure>
    <time_frame>At start and end of radiotherapy (duration of radiotherapy 7 weeks)</time_frame>
    <description>Dose and dose intensity including delay of scheduled therapy and absolute dose of radiotherapy applied.</description>
  </other_outcome>
  <other_outcome>
    <measure>Progression-free (PFS)</measure>
    <time_frame>From start until 3 months after end of RTX</time_frame>
    <description>The study will be finished one year post RTX and clinical al data on PFS will be obtained. In addition, patient will be asked to agree to collection of information regarding PFS even after completion of the trial.</description>
  </other_outcome>
  <other_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>From start until 3 months after end of RTX</time_frame>
    <description>The study will be finished one year post RTX and clinical data on OS will be obtained. In addition, patient will be asked to agree to collection of information regarding OS even after completion of the trial.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Squamous Cell Carcinoma of the Hypopharynx Stage III</condition>
  <condition>Squamous Cell Carcinoma of the Hypopharynx Stage IV</condition>
  <condition>Laryngeal Squamous Cell Carcinoma Stage III</condition>
  <condition>Laryngeal Squamous Cell Carcinoma Stage IV</condition>
  <condition>Oropharyngeal Squamous Cell Carcinoma Stage III</condition>
  <condition>Oropharyngeal Squamous Cell Carcinoma Stage IV</condition>
  <condition>Squamous Cell Carcinoma of the Oral Cavity Stage III</condition>
  <condition>Squamous Cell Carcinoma of the Oral Cavity Stage IV</condition>
  <condition>Locally Advanced Malignant Neoplasm</condition>
  <arm_group>
    <arm_group_label>Arm A - Standard of care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard care of parenteral nutrition (with or without parenteral nutrition during radio-chemotherapy or radio-immunotherapy in combination with Cetuximab or Cisplatin.&#xD;
Concomitant radiotherapy and immunotherapy (radio-immunotherapy) with Cetuximab or concomitant radiotherapy and chemotherapy (radio-chemotherapy) with Cisplatin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B - Parenteral over night nutrition</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Parenteral over night nutrition with ZentroOLIMEL 5.7% parenteral over night with electrolytes, vitamins (Cernevit®) and micronutrients (Addel Trace® or Nutryelt®) 15 ml/kg body weight/day (weight loss &gt;5% from baseline; parenteral nutrition increased up to 25 ml/kg body weight per day) during radio-chemotherapy or radio-immunotherapy in combination with Cetuximab or Cisplatin.&#xD;
Concomitant radiotherapy and immunotherapy (radio-immunotherapy) with Cetuximab or concomitant radiotherapy and chemotherapy (radio-chemotherapy) with Cisplatin</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Standard care of parenteral nutrition</intervention_name>
    <description>Standard treatment according to the discretion of the center, any required nutritional support (enteral tube feeding by nasogastric tube or percutaneous endoscopic gastrostomy) when considered necessary is allowed</description>
    <arm_group_label>Arm A - Standard of care</arm_group_label>
    <other_name>PN</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Parenteral over night nutrition</intervention_name>
    <description>Patients in interventional Arm B will receive parenteral overnight nutrition with ZentroOLIMEL® 5.7% with electrolytes, vitamins (Cernevit®) and micronutrients (Addel Trace® or Nutryelt®) starting with 15 ml/kg body weight/day. In case of weight loss of more than 5%, dose of ZentroOLIMEL® has to be increased up to 25 ml/kg/body weight/day.</description>
    <arm_group_label>Arm B - Parenteral over night nutrition</arm_group_label>
    <other_name>Emulsion for infusion</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Cetuximab</intervention_name>
    <description>Weekly during radiotherapy; not given if cisplatin is given during radiotherapy&#xD;
Cetuximab 400 mg/m2 (saturation) Cetuximab 250mg/m2 (during radiotherapy; in total 7x)</description>
    <arm_group_label>Arm A - Standard of care</arm_group_label>
    <arm_group_label>Arm B - Parenteral over night nutrition</arm_group_label>
    <other_name>Erbitux</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Cisplatin total dose of &gt;200 mg administered weekly (40 mg/m2/week) or every three weeks (100 mg/m2 every three weeks) according to local standard; not given in combination with cetuximab</description>
    <arm_group_label>Arm A - Standard of care</arm_group_label>
    <arm_group_label>Arm B - Parenteral over night nutrition</arm_group_label>
    <other_name>Cisplatinum</other_name>
    <other_name>CDDP</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiotherapy</intervention_name>
    <description>70 Gy / 5 fractions per week, over 7 weeks</description>
    <arm_group_label>Arm A - Standard of care</arm_group_label>
    <arm_group_label>Arm B - Parenteral over night nutrition</arm_group_label>
    <other_name>RTX</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Any patient who is eligible for definitive curative radio-chemotherapy with Cisplatin&#xD;
             or radio-immunotherapy with Cetuximab.&#xD;
&#xD;
          -  Written informed consent obtained prior to any study specific screening activities and&#xD;
             patients have to be able to comply with this protocol.&#xD;
&#xD;
          -  Histologically confirmed local advanced squamous cell carcinoma of the Larynx,&#xD;
             Hypopharynx, Oropharynx or Cavum oris treated with definitive radiotherapy in&#xD;
             combination with Cisplatin or Cetuximab.&#xD;
&#xD;
          -  p16 status available&#xD;
&#xD;
          -  Age ≥ 18&#xD;
&#xD;
          -  Women of childbearing potential must have a negative pregnancy test at screening and&#xD;
             must use effective contraception.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Distant metastases&#xD;
&#xD;
          -  Prior radiation (Head and neck area)&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  History of other malignancy; yet patients who have been disease-free for 5 years or&#xD;
             patients with a history of completely resected non-melanoma skin cancer or&#xD;
             successfully treated in situ carcinoma are eligible.&#xD;
&#xD;
          -  Concurrent other cancer therapy (chemotherapy, immunotherapy, antihormonal or biologic&#xD;
             therapy) or concurrent treatment with an investigational drug.&#xD;
&#xD;
          -  Serious medical or psychiatric disorders that would interfere with the patient's&#xD;
             safety or informed consent.&#xD;
&#xD;
          -  Participation in another interventional clinical study at time of study inclusion&#xD;
             (except follow-up period without treatment for more than 30 days) or denial of the&#xD;
             simultaneous participation in a non-interventional study by the PI of the study&#xD;
             center.&#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>Felix Keil, Prof.Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hanuschkrankenhaus</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Landeskrankenhaus Feldkirch</name>
      <address>
        <city>Feldkirch</city>
        <zip>A-6807</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Universität Graz, HNO Universitätsklinik</name>
      <address>
        <city>Graz</city>
        <zip>A-8036</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum Klagenfurt am Wörthersee, HNO-Abteilung</name>
      <address>
        <city>Klagenfurt am Wörthersee</city>
        <zip>A-9020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ordensklinikum Linz - Barmherzigen Schwestern, Abteilung f. HNO, Kopf- und Halschirurgie</name>
      <address>
        <city>Linz</city>
        <zip>4010</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hanuschkrankenhaus</name>
      <address>
        <city>Vienna</city>
        <zip>1140</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Landesklinikum Wiener Neustadt</name>
      <address>
        <city>Wiener Neustadt</city>
        <zip>2700</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Krankenhaus Hietzing, Sonderabteilung f. Strahlentheapie</name>
      <address>
        <city>Wien</city>
        <zip>1130</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <link>
    <url>http://www.agmt.at</url>
    <description>Sponsor</description>
  </link>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>September 5, 2014</study_first_submitted>
  <study_first_submitted_qc>September 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2014</study_first_posted>
  <last_update_submitted>April 30, 2020</last_update_submitted>
  <last_update_submitted_qc>April 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 1, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Squamous Cell Carcinoma</keyword>
  <keyword>Head and neck</keyword>
  <keyword>SCCHN</keyword>
  <keyword>Parenteral nutrition</keyword>
  <keyword>Larynx</keyword>
  <keyword>Hypopharynx</keyword>
  <keyword>Cavum oris</keyword>
  <keyword>Radiotherapy</keyword>
  <keyword>Cetuximab</keyword>
  <keyword>Cisplatin</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>Neoplasms</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
    <mesh_term>Head and Neck Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cetuximab</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/NCT02236936
org study id: AGMT_HNO_PN
nct id: NCT02236936
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Prevention of critical weight loss. In patients with Squamous Cell Carcinoma of the Head and
      Neck (SCCHN) weight loss is a relevant clinical problem during radiotherapy and might result
      in higher treatment related toxicity and discontinuation of a potential curative treatment.
      Thus the investigators want to evaluate the efficacy of overnight parenteral nutritional (PN)
      support in patients with SCCHN treated with curative radiotherapy (RTX) in combination with
      Cetuximab (E) or Cisplatin (P).
The investigators hypothesize that about 60% of patients receiving RTX without supplemental
      PN will suffer from critical weight loss of more than 5% during treatment - supplemental
      overnight PN might result in significant improvement of the nutritional status .
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Loss of body weight by more than 5% at the end of radiotherapy
time frame: Difference between baseline and week 8 (after end of RTX)
description: Weekly body weight assessments - standardized method for all study sites
measure: Bioelectrical Impedance Analysis (BIA): reduction of phase angle by > 10% during treatment/observation
time frame: Prior to and 1 year after start of RTX, within 7 days and 3 months after end of RTX
description: Determination of parameters on functional nutritional status: fat-free mass (FFM), total body water (TBW), body fat and phase angle will be evaluated by BIA
measure: Assessment of physical strength
time frame: Prior to RTX, weekly during RTX, within 1 week and 3 months after end of RTX
description: Handgrip strength measurement, mean value of three consecutive measurements
measure: Number of implanted PEG tubes
time frame: From start of RTX until 3 months after end of RTX
description: The number of implanted PEG tubes will be recorded
measure: Acute toxicity during radiotherapy
time frame: During 7 weeks of radiotherapy, at end of radiotherapy and 3 months after radiotherapy
description: Acute toxicity according to Common Terminology Criteria for Adverse Events (CTCAE 4.0.)
measure: Chronic toxicity after treatment
time frame: 3 months after end of radiotherapy
description: Chronic toxicity evaluated according to RTOG (Radiation Therapy Oncology Group)/EORTC (European Organisation for Research and Treatment of Cancer) - Toxicity Criteria
measure: Dose and dose intensity of radiotherapy
time frame: At start and end of radiotherapy (duration of radiotherapy 7 weeks)
description: Dose and dose intensity including delay of scheduled therapy and absolute dose of radiotherapy applied.
measure: Progression-free (PFS)
time frame: From start until 3 months after end of RTX
description: The study will be finished one year post RTX and clinical al data on PFS will be obtained. In addition, patient will be asked to agree to collection of information regarding PFS even after completion of the trial.
measure: Overall survival (OS)
time frame: From start until 3 months after end of RTX
description: The study will be finished one year post RTX and clinical data on OS will be obtained. In addition, patient will be asked to agree to collection of information regarding OS even after completion of the trial.
arm group label: Arm A - Standard of care
arm group type: Active Comparator
description: Standard care of parenteral nutrition (with or without parenteral nutrition during radio-chemotherapy or radio-immunotherapy in combination with Cetuximab or Cisplatin.
Concomitant radiotherapy and immunotherapy (radio-immunotherapy) with Cetuximab or concomitant radiotherapy and chemotherapy (radio-chemotherapy) with Cisplatin
arm group label: Arm B - Parenteral over night nutrition
arm group type: Experimental
description: Parenteral over night nutrition with ZentroOLIMEL 5.7% parenteral over night with electrolytes, vitamins (Cernevit®) and micronutrients (Addel Trace® or Nutryelt®) 15 ml/kg body weight/day (weight loss >5% from baseline; parenteral nutrition increased up to 25 ml/kg body weight per day) during radio-chemotherapy or radio-immunotherapy in combination with Cetuximab or Cisplatin.
Concomitant radiotherapy and immunotherapy (radio-immunotherapy) with Cetuximab or concomitant radiotherapy and chemotherapy (radio-chemotherapy) with Cisplatin
intervention type: Dietary Supplement
intervention name: Standard care of parenteral nutrition
description: Standard treatment according to the discretion of the center, any required nutritional support (enteral tube feeding by nasogastric tube or percutaneous endoscopic gastrostomy) when considered necessary is allowed
arm group label: Arm A - Standard of care
other name: PN
intervention type: Dietary Supplement
intervention name: Parenteral over night nutrition
description: Patients in interventional Arm B will receive parenteral overnight nutrition with ZentroOLIMEL® 5.7% with electrolytes, vitamins (Cernevit®) and micronutrients (Addel Trace® or Nutryelt®) starting with 15 ml/kg body weight/day. In case of weight loss of more than 5%, dose of ZentroOLIMEL® has to be increased up to 25 ml/kg/body weight/day.
arm group label: Arm B - Parenteral over night nutrition
other name: Emulsion for infusion
intervention type: Biological
intervention name: Cetuximab
description: Weekly during radiotherapy; not given if cisplatin is given during radiotherapy
Cetuximab 400 mg/m2 (saturation) Cetuximab 250mg/m2 (during radiotherapy; in total 7x)
arm group label: Arm A - Standard of care
arm group label: Arm B - Parenteral over night nutrition
other name: Erbitux
intervention type: Drug
intervention name: Cisplatin
description: Cisplatin total dose of >200 mg administered weekly (40 mg/m2/week) or every three weeks (100 mg/m2 every three weeks) according to local standard; not given in combination with cetuximab
arm group label: Arm A - Standard of care
arm group label: Arm B - Parenteral over night nutrition
other name: Cisplatinum
other name: CDDP
intervention type: Radiation
intervention name: Radiotherapy
description: 70 Gy / 5 fractions per week, over 7 weeks
arm group label: Arm A - Standard of care
arm group label: Arm B - Parenteral over night nutrition
other name: RTX
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Felix Keil, Prof.Dr.
role: Principal Investigator
affiliation: Hanuschkrankenhaus
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Austria
url: http://www.agmt.at
description: Sponsor
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Neoplasms
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Head and Neck Neoplasms
mesh term: Cetuximab