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A Study of Chemoradiotherapy Followed by Planned Surgery or by Surveillance and Surgery Only When Needed for Cancer of the Esophagus (NEEDS)

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ClinicalTrials.gov Identifier: NCT04460352
Recruitment Status : Recruiting
First Posted : July 7, 2020
Last Update Posted : December 3, 2020
Sponsor:
Collaborators:
University of Leipzig
The Swedish Research Council
Information provided by (Responsible Party):
Magnus Nilsson, Karolinska University Hospital

Tracking Information
First Submitted Date  ICMJE June 25, 2020
First Posted Date  ICMJE July 7, 2020
Last Update Posted Date December 3, 2020
Actual Study Start Date  ICMJE November 27, 2020
Estimated Primary Completion Date September 18, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 1, 2020)
Overall survival [ Time Frame: 5 years after randomisation ]
When 266 events have occurred
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 1, 2020)
  • Global Health-related quality of life (HRQOL) [ Time Frame: 1 year after randomisation ]
    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).
  • 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 ]
    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).
  • 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 ]
    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).
  • 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 ]
    The EuroQoL Group's EQ-5D-5L questionnaire consisting of five dimensions ranging from No problems to Extreme problems or Unable to care.
  • Event-free survival [ Time Frame: 5 years after randomisation ]
    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.
  • Loco-regional and distant relapse rates [ Time Frame: 5 years after randomisation ]
    Including the relation of relapse location to the radiation field
  • Histopathological response according to Mandard in operated patients [ Time Frame: 5 years after randomisation ]
    ypTNM including total and metastatic lymph node count, tumor free resection margins, R0
  • Health economy [ Time Frame: At baseline and 6, 12, 24, 36 and 60 months after randomisation ]
    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
  • Surgical complications [ Time Frame: After surgery in operated patients, up to 5 years after randomisation ]
    According to the Esophagectomy Complications Consensus Group (ECCG) and classified according to Clavien-Dindo
  • Treatment-related adverse events and toxicity [ Time Frame: Up to 5 years after randomisation ]
    NCI-CTCAE Criteria version 5.0
  • Nutritional outcomes - weight [ Time Frame: Up to 5 years after randomisation ]
    Weight development. Weight (in kg) will be measured at all visits.
  • Nutritional outcomes - dysphagia [ Time Frame: Up to 5 years after randomisation ]
    Dysphagia will be evaluated at all visits according to the CTC adverse event scale, grading from 0 (no problems) to 4 (worst problems).
  • Gender stratified analyses of all endpoints [ Time Frame: Up to 5 years after randomisation ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Chemoradiotherapy Followed by Planned Surgery or by Surveillance and Surgery Only When Needed for Cancer of the Esophagus
Official Title  ICMJE NEoadjuvant Chemoradiotherapy for Esophageal Squamous Cell Carcinoma Versus Definitive Chemoradiotherapy With Salvage Surgery as Needed (NEEDS Trial)
Brief Summary

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Esophageal Squamous Cell Carcinoma
Intervention  ICMJE
  • Radiation: Neoadjuvant radiotherapy (arm A)
    1.8 Gy fractions 5 days per week in 23 fractions to a total dose of 41.4 Gy.
  • Drug: Carboplatin, paclitaxel
    Carboplatin AUC 2 + Paclitaxel 50mg/m2 weekly x 5 (day 1, 8, 15, 22, 29), starting same day as radiotherapy
    Other Name: Neoadjuvant chemotherapy
  • Procedure: Esophagectomy
    Esophagectomy performed within 8 weeks after termination of chemoradiotherapy
  • Radiation: Neoadjuvant radiotherapy (arm B)

    Two alternative schemes:

    1. 1.8 Gy fractions five days per week in 28 fractions to a total dose of 50.4 Gy.
    2. 2.0 Gy fractions five days per week in 25 fractions to a total dose of 50 Gy.
  • Drug: Carboplatin, paclitaxel
    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).
    Other Name: Neoadjuvant Platin-Taxane Regimen (alternative 1)
  • Drug: Cisplatin, paclitaxel
    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.
    Other Name: Platinum-Fluoropyrimidine Regimens (alternative 2a)
  • Drug: Oxaliplatin, calcium folinate, 5-fluorouracil
    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.
    Other Name: Platinum-Fluoropyrimidine Regimens (alternative 2b)
  • Procedure: Esophagectomy
    Esophagectomy only in case of residual or recurrent locoregional cancer.
Study Arms  ICMJE
  • Active Comparator: Control arm (A)

    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,

    Interventions:
    • Radiation: Neoadjuvant radiotherapy (arm A)
    • Drug: Carboplatin, paclitaxel
    • Procedure: Esophagectomy
  • Experimental: Experimental arm (B)

    Definitive chemoradiotherapy followed by surveillance, and esophagectomy only in case of residual or recurrent locoregional cancer.

    Radiotherapy: Two alternative schemes:

    1. 1.8 Gy fractions five days per week in 28 fractions to a total dose of 50.4 Gy.
    2. 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.

    Interventions:
    • Radiation: Neoadjuvant radiotherapy (arm B)
    • Drug: Carboplatin, paclitaxel
    • Drug: Cisplatin, paclitaxel
    • Drug: Oxaliplatin, calcium folinate, 5-fluorouracil
    • Procedure: Esophagectomy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 1, 2020)
1200
Original Estimated Enrollment  ICMJE
 (submitted: July 1, 2020)
1000
Estimated Study Completion Date  ICMJE December 31, 2031
Estimated Primary Completion Date September 18, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histopathologically confirmed SCC of the esophagus in locally advanced stages cT1 N+ or cT2-4a any N, M0, according to current (8th) version of of the AJCC TNM classification.
  • Technically resectable disease according to the local multidisciplinary team conference (MDT)/tumor board.
  • Performance status ECOG 0-1.
  • Adequate organ function.
  • Women of childbearing potential (WOCBP*) must have a negative serum or urine pregnancy test.
  • Patients of childbearing/reproductive potential should use highly effective method of birth control measures during the study treatment period and for at least five months after the last study treatment.
  • Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment.
  • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
  • Before patient registration/randomization, written informed consent must be given according to ICH/GCP/GDPR and national/local regulations.

Exclusion Criteria:

  • M1 according to current (8th) version of of the AJCC TNM classification.
  • cT4b according to current (8th) version of of the AJCC TNM classification.
  • Primary tumor not resectable without laryngectomy.
  • Impaired renal, hepatic, cardiac, pulmonary or endocrine status that compromises the eligibility of the patient for multimodality treatment with chemoradiotherapy followed by esophagectomy.
  • Subjects not considered likely to tolerate multimodality treatment with chemoradiotherapy followed by esophagectomy.
  • Subjects with previous malignancies are excluded unless a complete remission or complete resection was achieved at least 5 years prior to study entry.
  • Prior or concomitant treatment with radiotherapy or chemoradiotherapy with potential overlap of radiotherapy fields.
  • Known uncontrollable hypersensitivity to the components of the chemotherapeutic agents used in the trial regimens.
  • Inability to fully understand and digest study patient information or to comply with study instructions due to language difficulty or cognitive failure such as dementia or severe psychiatric disorder.

(Criteria slightly shortened)

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Magnus Nilsson, MD, PhD +46-707-375186 magnus.nilsson@ki.se
Contact: Mats Hellström +46-8-51773677 mats.hellstrom@sll.se
Listed Location Countries  ICMJE Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04460352
Other Study ID Numbers  ICMJE NEEDS
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Magnus Nilsson, Karolinska University Hospital
Study Sponsor  ICMJE Karolinska University Hospital
Collaborators  ICMJE
  • University of Leipzig
  • The Swedish Research Council
Investigators  ICMJE
Study Chair: Magnus Nilsson, MD, PhD Karolinska University Hospital
Study Chair: Florian Lordick, MD, PhD Leipzig University Medical Center
PRS Account Karolinska University Hospital
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP