<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/NCT04460352</url>
  </required_header>
  <id_info>
    <org_study_id>NEEDS</org_study_id>
    <nct_id>NCT04460352</nct_id>
  </id_info>
  <brief_title>Chemoradiotherapy Followed by Planned Surgery or by Surveillance and Surgery Only When Needed for Oesophageal Cancer</brief_title>
  <acronym>NEEDS</acronym>
  <official_title>NEoadjuvant Chemoradiotherapy for Esophageal Squamous Cell Carcinoma Versus Definitive Chemoradiotherapy With Salvage Surgery as Needed (NEEDS Trial)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Karolinska University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Leipzig</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Swedish Research Council</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Karolinska University Hospital</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>
      NEEDS is a pragmatic open-label, randomised, controlled, phase III, multicenter trial with&#xD;
      non-inferiority design with regard to the primary endpoint overall survival and superiority&#xD;
      for the experimental intervention definitive chemoradiotherapy with regard to the main&#xD;
      secondary endpoint global health related quality of life (HRQOL) one year after&#xD;
      randomisation.&#xD;
&#xD;
      The aim is to compare outcomes after neoadjuvant chemoradiotherapy with subsequent&#xD;
      esophagectomy to definitive chemoradiotherapy with surveillance and salvage esophagectomy as&#xD;
      needed in patients with resectable locally advanced squamous cell carcinoma (SCC) of the&#xD;
      esophagus, with the aim to provide generalisable guidance for future clinical practice.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 27, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2031</completion_date>
  <primary_completion_date type="Anticipated">September 18, 2026</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>
    <intervention_model_description>NEEDS is a pragmatic open-label, randomised, controlled, phase III, multicenter trial with non-inferiority design with regard to the primary endpoint overall survival and superiority for the experimental intervention definitive chemoradiotherapy with regard to the main secondary endpoint global health related quality of life (HRQOL) one year after randomisation</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall survival</measure>
    <time_frame>5 years after randomisation</time_frame>
    <description>When 266 events have occurred</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Global Health-related quality of life (HRQOL)</measure>
    <time_frame>1 year after randomisation</time_frame>
    <description>European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30, version 3.0 (EORTC QLQ-C30). The two items assessing global health and overall quality of life are responded to in seven categories ranging from 1 (very poor) to 7 (excellent).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health related quality of life of Cancer patients</measure>
    <time_frame>At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation</time_frame>
    <description>EORTC HRQOL Questionnaire QLQ-C30 version 3.0, 28 items ranging from 1 (no problems at all) to 4 (very much) and two items assessing global health and overall quality of life are responded to in seven categories ranging from 1 (very poor) to 7 (excellent).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health related quality of life, oesophageal specific.</measure>
    <time_frame>At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation</time_frame>
    <description>EORTC HRQOL gastresophageal-specific questionnaire EORTC QLQ-OG25. 25 items assessing symptoms or problems are responded to in four categories ranging from 1 (no problems) to 4 (very much).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health related quality of life, general health</measure>
    <time_frame>At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation</time_frame>
    <description>The EuroQoL Group's EQ-5D-5L questionnaire consisting of five dimensions ranging from No problems to Extreme problems or Unable to care.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-free survival</measure>
    <time_frame>5 years after randomisation</time_frame>
    <description>Time to relapse, initiation of any anti-tumor therapy beyond the study treatments (salvage surgery is considered a study treatment in the dCRT arm), or death, whichever comes first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Loco-regional and distant relapse rates</measure>
    <time_frame>5 years after randomisation</time_frame>
    <description>Including the relation of relapse location to the radiation field</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Histopathological response according to Mandard in operated patients</measure>
    <time_frame>5 years after randomisation</time_frame>
    <description>ypTNM including total and metastatic lymph node count, tumor free resection margins, R0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health economy</measure>
    <time_frame>At baseline and 6, 12, 24, 36 and 60 months after randomisation</time_frame>
    <description>Assessed including patient-level medical resource use and societal costs due to sick-leave and other non-medical costs. Quality-adjusted life years (QALYs) will be calculated using EQ-5D</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Surgical complications</measure>
    <time_frame>After surgery in operated patients, up to 5 years after randomisation</time_frame>
    <description>According to the Esophagectomy Complications Consensus Group (ECCG) and classified according to Clavien-Dindo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment-related adverse events and toxicity</measure>
    <time_frame>Up to 5 years after randomisation</time_frame>
    <description>NCI-CTCAE Criteria version 5.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nutritional outcomes - weight</measure>
    <time_frame>Up to 5 years after randomisation</time_frame>
    <description>Weight development. Weight (in kg) will be measured at all visits.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nutritional outcomes - dysphagia</measure>
    <time_frame>Up to 5 years after randomisation</time_frame>
    <description>Dysphagia will be evaluated at all visits according to the CTC adverse event scale, grading from 0 (no problems) to 4 (worst problems).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gender stratified analyses of all endpoints</measure>
    <time_frame>Up to 5 years after randomisation</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">1200</enrollment>
  <condition>Esophageal Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Control arm (A)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Neoadjuvant chemoradiotherapy followed by esophagectomy.&#xD;
Radiotherapy: 1.8 Gy fractions 5 days per week in 23 fractions to a total dose of 41.4 Gy.&#xD;
Chemotherapy: Carboplatin AUC 2 + Paclitaxel 50mg/m2 weekly x 5 (day 1, 8, 15, 22, 29), starting on the first day of radiotherapy.&#xD;
Esophagectomy: Within 8 weeks of termination of chemoradiotherapy,</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Experimental arm (B)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Definitive chemoradiotherapy followed by surveillance, and esophagectomy only in case of residual or recurrent locoregional cancer.&#xD;
Radiotherapy: Two alternative schemes:&#xD;
1.8 Gy fractions five days per week in 28 fractions to a total dose of 50.4 Gy.&#xD;
2.0 Gy fractions five days per week in 25 fractions to a total dose of 50 Gy.&#xD;
Chemotherapy: Three alternative regimens:&#xD;
1. Platin-Taxane Regimen: Carboplatin AUC 2 + Paclitaxel 50mg/m2 on day 1 weekly during the full course of radiotherapy.&#xD;
2a. Platinum-Fluoropyrimidine Regimen: Cisplatin 75mg/m2 weeks 1 and 5 + 5-fluorouracil 1000 mg/m2/day by continuous infusion weeks 1 and 5.&#xD;
2b. FOLFOX: Oxaliplatin 85 mg/m2, calcium folinate 200 mg/m2 and 5-fluorouracil 400 mg/m2 weeks 1, 3 and 5 + 5-fluorouracil 800 mg/m2 by continuous infusion weeks 1, 3 and 5.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Neoadjuvant radiotherapy (arm A)</intervention_name>
    <description>1.8 Gy fractions 5 days per week in 23 fractions to a total dose of 41.4 Gy.</description>
    <arm_group_label>Control arm (A)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin, paclitaxel</intervention_name>
    <description>Carboplatin AUC 2 + Paclitaxel 50mg/m2 weekly x 5 (day 1, 8, 15, 22, 29), starting same day as radiotherapy</description>
    <arm_group_label>Control arm (A)</arm_group_label>
    <other_name>Neoadjuvant chemotherapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Esophagectomy</intervention_name>
    <description>Esophagectomy performed within 8 weeks after termination of chemoradiotherapy</description>
    <arm_group_label>Control arm (A)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Neoadjuvant radiotherapy (arm B)</intervention_name>
    <description>Two alternative schemes:&#xD;
1.8 Gy fractions five days per week in 28 fractions to a total dose of 50.4 Gy.&#xD;
2.0 Gy fractions five days per week in 25 fractions to a total dose of 50 Gy.</description>
    <arm_group_label>Experimental arm (B)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin, paclitaxel</intervention_name>
    <description>Carboplatin AUC 2 + Paclitaxel 50mg/m2 on day 1 weekly during the full course of radiotherapy (5 weeks or 6 weeks, depending on the radiotherapy regimen used).</description>
    <arm_group_label>Experimental arm (B)</arm_group_label>
    <other_name>Neoadjuvant Platin-Taxane Regimen (alternative 1)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin, paclitaxel</intervention_name>
    <description>Cisplatin 75mg/m2 on the first day of weeks 1 and 5 + 5-fluorouracil 1000 mg/m2/day by continuous infusion on the first four days of weeks 1 and 5.</description>
    <arm_group_label>Experimental arm (B)</arm_group_label>
    <other_name>Platinum-Fluoropyrimidine Regimens (alternative 2a)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin, calcium folinate, 5-fluorouracil</intervention_name>
    <description>FOLFOX: Oxaliplatin 85 mg/m2, calcium folinate 200 mg/m2 and 5-fluorouracil 400 mg/m2 on the first days of weeks 1, 3 and 5 + 5-fluorouracil 800 mg/m2 by continuous infusion on the first two days of weeks 1, 3 and 5.</description>
    <arm_group_label>Experimental arm (B)</arm_group_label>
    <other_name>Platinum-Fluoropyrimidine Regimens (alternative 2b)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Esophagectomy</intervention_name>
    <description>Esophagectomy only in case of residual or recurrent locoregional cancer.</description>
    <arm_group_label>Experimental arm (B)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histopathologically confirmed SCC of the esophagus in locally advanced stages cT1 N+&#xD;
             or cT2-4a any N, M0, according to current (8th) version of of the AJCC TNM&#xD;
             classification.&#xD;
&#xD;
          -  Technically resectable disease according to the local multidisciplinary team&#xD;
             conference (MDT)/tumor board.&#xD;
&#xD;
          -  Performance status ECOG 0-1.&#xD;
&#xD;
          -  Adequate organ function.&#xD;
&#xD;
          -  Women of childbearing potential (WOCBP*) must have a negative serum or urine pregnancy&#xD;
             test.&#xD;
&#xD;
          -  Patients of childbearing/reproductive potential should use highly effective method of&#xD;
             birth control measures during the study treatment period and for at least five months&#xD;
             after the last study treatment.&#xD;
&#xD;
          -  Female subjects who are breast feeding should discontinue nursing prior to the first&#xD;
             dose of study treatment.&#xD;
&#xD;
          -  Absence of any psychological, familial, sociological or geographical condition&#xD;
             potentially hampering compliance with the study protocol and follow-up schedule.&#xD;
&#xD;
          -  Before patient registration/randomization, written informed consent must be given&#xD;
             according to ICH/GCP/GDPR and national/local regulations.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  M1 according to current (8th) version of of the AJCC TNM classification.&#xD;
&#xD;
          -  cT4b according to current (8th) version of of the AJCC TNM classification.&#xD;
&#xD;
          -  Primary tumor not resectable without laryngectomy.&#xD;
&#xD;
          -  Impaired renal, hepatic, cardiac, pulmonary or endocrine status that compromises the&#xD;
             eligibility of the patient for multimodality treatment with chemoradiotherapy followed&#xD;
             by esophagectomy.&#xD;
&#xD;
          -  Subjects not considered likely to tolerate multimodality treatment with&#xD;
             chemoradiotherapy followed by esophagectomy.&#xD;
&#xD;
          -  Subjects with previous malignancies are excluded unless a complete remission or&#xD;
             complete resection was achieved at least 5 years prior to study entry.&#xD;
&#xD;
          -  Prior or concomitant treatment with radiotherapy or chemoradiotherapy with potential&#xD;
             overlap of radiotherapy fields.&#xD;
&#xD;
          -  Known uncontrollable hypersensitivity to the components of the chemotherapeutic agents&#xD;
             used in the trial regimens.&#xD;
&#xD;
          -  Inability to fully understand and digest study patient information or to comply with&#xD;
             study instructions due to language difficulty or cognitive failure such as dementia or&#xD;
             severe psychiatric disorder.&#xD;
&#xD;
        (Criteria slightly shortened)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Magnus Nilsson, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Karolinska University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Florian Lordick, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Leipzig University Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Magnus Nilsson, MD, PhD</last_name>
    <phone>+46-707-375186</phone>
    <email>magnus.nilsson@ki.se</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Mats Hellström</last_name>
    <phone>+46-8-51773677</phone>
    <email>mats.hellstrom@sll.se</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Oslo universitetssykehus</name>
      <address>
        <city>Oslo</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Janne Christoffersen, RN</last_name>
      <email>jannec@ous-hf.no</email>
    </contact>
    <investigator>
      <last_name>Ghazwan Al-Haidari, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Universitetssykehuset Nord-Norge</name>
      <address>
        <city>Tromsø</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eirik Kjus Aahlin, MD, PhD</last_name>
      <email>eirik.kjus.aahlin@unn.no</email>
    </contact>
    <contact_backup>
      <last_name>Kristin Woll, RN</last_name>
      <email>kristin.woll@unn.no</email>
    </contact_backup>
    <investigator>
      <last_name>Eirik Kjus Aahlin, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>St Olavs Hospital</name>
      <address>
        <city>Trondheim</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marte Romundstad, RN</last_name>
      <email>marte.romunstad@stolav.no</email>
    </contact>
    <investigator>
      <last_name>Lars Cato Rekstad, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Linköpings universitetssjukhus</name>
      <address>
        <city>Linköping</city>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David Edholm, MD</last_name>
      <email>david.edholm@regionostergotland.se</email>
    </contact>
    <contact_backup>
      <last_name>Anna Lindhoff Larsson, RN</last_name>
      <email>anna.lindhoff.larsson@regionostergotland.se</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Skånes universitetssjukhus</name>
      <address>
        <city>Lund</city>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Monika Meszaros, RN</last_name>
      <email>monika.meszaros@skane.se</email>
    </contact>
    <contact_backup>
      <last_name>Marit Bakos, RN</last_name>
      <email>marit.bakos@skane.se</email>
    </contact_backup>
    <investigator>
      <last_name>Jan Johansson, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Karolinska University Hospital</name>
      <address>
        <city>Stockholm</city>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Berit Sunde, RN, PhD</last_name>
      <email>berit.sunde@ki.se</email>
    </contact>
    <contact_backup>
      <last_name>Maria Lampi, RN</last_name>
      <email>maria.lampi@regionstockholm.se</email>
    </contact_backup>
    <investigator>
      <last_name>Magnus Nilsson, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Gabriella Alexandersson von Döbeln, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Norrlands universitetssjukhus</name>
      <address>
        <city>Umeå</city>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Birgitta Orrvik Olsson, RN</last_name>
      <email>birgitta.orrvikolsson@regionvasterbotten.se</email>
    </contact>
    <contact_backup>
      <last_name>Agneta Karhu, RN</last_name>
      <email>agneta.karhu@regionvasterbotten.se</email>
    </contact_backup>
    <investigator>
      <last_name>Bengt Wallner, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Akademiska sjukhuset</name>
      <address>
        <city>Uppsala</city>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lena Ekfjord, RN</last_name>
      <email>lena.ekfjord@akademiska.se</email>
    </contact>
    <investigator>
      <last_name>Jakob Hedberg, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Örebro universitetssjukhus</name>
      <address>
        <city>Örebro</city>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Linnea Sundström, RN</last_name>
      <email>linnea.sundstrom@regionorebrolan.se</email>
    </contact>
    <investigator>
      <last_name>Eva Szabo, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Norway</country>
    <country>Sweden</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>June 25, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>March 29, 2022</last_update_submitted>
  <last_update_submitted_qc>March 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 31, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Karolinska University Hospital</investigator_affiliation>
    <investigator_full_name>Magnus Nilsson</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Neoadjuvant chemoradiotherapy</keyword>
  <keyword>Definitive chemoradiotherapy with salvage surgery as needed</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>
  </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>Albumin-Bound Paclitaxel</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
    <mesh_term>Calcium</mesh_term>
    <mesh_term>Levoleucovorin</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/NCT04460352
org study id: NEEDS
nct id: NCT04460352
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
NEEDS is a pragmatic open-label, randomised, controlled, phase III, multicenter trial with
      non-inferiority design with regard to the primary endpoint overall survival and superiority
      for the experimental intervention definitive chemoradiotherapy with regard to the main
      secondary endpoint global health related quality of life (HRQOL) one year after
      randomisation.

      The aim is to compare outcomes after neoadjuvant chemoradiotherapy with subsequent
      esophagectomy to definitive chemoradiotherapy with surveillance and salvage esophagectomy as
      needed in patients with resectable locally advanced squamous cell carcinoma (SCC) of the
      esophagus, with the aim to provide generalisable guidance for future clinical practice.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: NEEDS is a pragmatic open-label, randomised, controlled, phase III, multicenter trial with non-inferiority design with regard to the primary endpoint overall survival and superiority for the experimental intervention definitive chemoradiotherapy with regard to the main secondary endpoint global health related quality of life (HRQOL) one year after randomisation
primary purpose: Treatment
masking: None (Open Label)
measure: Overall survival
time frame: 5 years after randomisation
description: When 266 events have occurred
measure: Global Health-related quality of life (HRQOL)
time frame: 1 year after randomisation
description: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30, version 3.0 (EORTC QLQ-C30). The two items assessing global health and overall quality of life are responded to in seven categories ranging from 1 (very poor) to 7 (excellent).
measure: Health related quality of life of Cancer patients
time frame: At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation
description: EORTC HRQOL Questionnaire QLQ-C30 version 3.0, 28 items ranging from 1 (no problems at all) to 4 (very much) and two items assessing global health and overall quality of life are responded to in seven categories ranging from 1 (very poor) to 7 (excellent).
measure: Health related quality of life, oesophageal specific.
time frame: At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation
description: EORTC HRQOL gastresophageal-specific questionnaire EORTC QLQ-OG25. 25 items assessing symptoms or problems are responded to in four categories ranging from 1 (no problems) to 4 (very much).
measure: Health related quality of life, general health
time frame: At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation
description: The EuroQoL Group's EQ-5D-5L questionnaire consisting of five dimensions ranging from No problems to Extreme problems or Unable to care.
measure: Event-free survival
time frame: 5 years after randomisation
description: Time to relapse, initiation of any anti-tumor therapy beyond the study treatments (salvage surgery is considered a study treatment in the dCRT arm), or death, whichever comes first.
measure: Loco-regional and distant relapse rates
time frame: 5 years after randomisation
description: Including the relation of relapse location to the radiation field
measure: Histopathological response according to Mandard in operated patients
time frame: 5 years after randomisation
description: ypTNM including total and metastatic lymph node count, tumor free resection margins, R0
measure: Health economy
time frame: At baseline and 6, 12, 24, 36 and 60 months after randomisation
description: Assessed including patient-level medical resource use and societal costs due to sick-leave and other non-medical costs. Quality-adjusted life years (QALYs) will be calculated using EQ-5D
measure: Surgical complications
time frame: After surgery in operated patients, up to 5 years after randomisation
description: According to the Esophagectomy Complications Consensus Group (ECCG) and classified according to Clavien-Dindo
measure: Treatment-related adverse events and toxicity
time frame: Up to 5 years after randomisation
description: NCI-CTCAE Criteria version 5.0
measure: Nutritional outcomes - weight
time frame: Up to 5 years after randomisation
description: Weight development. Weight (in kg) will be measured at all visits.
measure: Nutritional outcomes - dysphagia
time frame: Up to 5 years after randomisation
description: Dysphagia will be evaluated at all visits according to the CTC adverse event scale, grading from 0 (no problems) to 4 (worst problems).
measure: Gender stratified analyses of all endpoints
time frame: Up to 5 years after randomisation
arm group label: Control arm (A)
arm group type: Active Comparator
description: Neoadjuvant chemoradiotherapy followed by esophagectomy.
Radiotherapy: 1.8 Gy fractions 5 days per week in 23 fractions to a total dose of 41.4 Gy.
Chemotherapy: Carboplatin AUC 2 + Paclitaxel 50mg/m2 weekly x 5 (day 1, 8, 15, 22, 29), starting on the first day of radiotherapy.
Esophagectomy: Within 8 weeks of termination of chemoradiotherapy,
arm group label: Experimental arm (B)
arm group type: Experimental
description: Definitive chemoradiotherapy followed by surveillance, and esophagectomy only in case of residual or recurrent locoregional cancer.
Radiotherapy: Two alternative schemes:
1.8 Gy fractions five days per week in 28 fractions to a total dose of 50.4 Gy.
2.0 Gy fractions five days per week in 25 fractions to a total dose of 50 Gy.
Chemotherapy: Three alternative regimens:
1. Platin-Taxane Regimen: Carboplatin AUC 2 + Paclitaxel 50mg/m2 on day 1 weekly during the full course of radiotherapy.
2a. Platinum-Fluoropyrimidine Regimen: Cisplatin 75mg/m2 weeks 1 and 5 + 5-fluorouracil 1000 mg/m2/day by continuous infusion weeks 1 and 5.
2b. FOLFOX: Oxaliplatin 85 mg/m2, calcium folinate 200 mg/m2 and 5-fluorouracil 400 mg/m2 weeks 1, 3 and 5 + 5-fluorouracil 800 mg/m2 by continuous infusion weeks 1, 3 and 5.
intervention type: Radiation
intervention name: Neoadjuvant radiotherapy (arm A)
description: 1.8 Gy fractions 5 days per week in 23 fractions to a total dose of 41.4 Gy.
arm group label: Control arm (A)
intervention type: Drug
intervention name: Carboplatin, paclitaxel
description: Carboplatin AUC 2 + Paclitaxel 50mg/m2 weekly x 5 (day 1, 8, 15, 22, 29), starting same day as radiotherapy
arm group label: Control arm (A)
other name: Neoadjuvant chemotherapy
intervention type: Procedure
intervention name: Esophagectomy
description: Esophagectomy performed within 8 weeks after termination of chemoradiotherapy
arm group label: Control arm (A)
intervention type: Radiation
intervention name: Neoadjuvant radiotherapy (arm B)
description: Two alternative schemes:
1.8 Gy fractions five days per week in 28 fractions to a total dose of 50.4 Gy.
2.0 Gy fractions five days per week in 25 fractions to a total dose of 50 Gy.
arm group label: Experimental arm (B)
intervention type: Drug
intervention name: Carboplatin, paclitaxel
description: Carboplatin AUC 2 + Paclitaxel 50mg/m2 on day 1 weekly during the full course of radiotherapy (5 weeks or 6 weeks, depending on the radiotherapy regimen used).
arm group label: Experimental arm (B)
other name: Neoadjuvant Platin-Taxane Regimen (alternative 1)
intervention type: Drug
intervention name: Cisplatin, paclitaxel
description: Cisplatin 75mg/m2 on the first day of weeks 1 and 5 + 5-fluorouracil 1000 mg/m2/day by continuous infusion on the first four days of weeks 1 and 5.
arm group label: Experimental arm (B)
other name: Platinum-Fluoropyrimidine Regimens (alternative 2a)
intervention type: Drug
intervention name: Oxaliplatin, calcium folinate, 5-fluorouracil
description: FOLFOX: Oxaliplatin 85 mg/m2, calcium folinate 200 mg/m2 and 5-fluorouracil 400 mg/m2 on the first days of weeks 1, 3 and 5 + 5-fluorouracil 800 mg/m2 by continuous infusion on the first two days of weeks 1, 3 and 5.
arm group label: Experimental arm (B)
other name: Platinum-Fluoropyrimidine Regimens (alternative 2b)
intervention type: Procedure
intervention name: Esophagectomy
description: Esophagectomy only in case of residual or recurrent locoregional cancer.
arm group label: Experimental arm (B)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Magnus Nilsson, MD, PhD
role: Study Chair
affiliation: Karolinska University Hospital
last name: Florian Lordick, MD, PhD
role: Study Chair
affiliation: Leipzig University Medical Center
last name: Magnus Nilsson, MD, PhD
phone: +46-707-375186
email: magnus.nilsson@ki.se
last name: Mats Hellström
phone: +46-8-51773677
email: mats.hellstrom@sll.se
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status: Recruiting
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country: Norway
country: Sweden
responsible party type: Principal Investigator
investigator affiliation: Karolinska University Hospital
investigator full name: Magnus Nilsson
investigator title: Professor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Esophageal Squamous Cell Carcinoma
mesh term: Leucovorin
mesh term: Paclitaxel
mesh term: Albumin-Bound Paclitaxel
mesh term: Carboplatin
mesh term: Fluorouracil
mesh term: Oxaliplatin
mesh term: Calcium
mesh term: Levoleucovorin
sharing ipd: No