NEEDS is a pragmatic open-label, randomised, controlled, phase III, multicenter trial with non-inferiority design with regard to the first co-primary endpoint overall survival and superiority for the experimental intervention definitive chemoradiotherapy. A second co-primary endpoint is global health related quality of life (HRQOL) one year after randomisation. A third co-primary endpoint is eating restictions 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1,020
1.8 Gy fractions 5 days per week in 23 fractions to a total dose of 41.4 Gy.
Carboplatin AUC 2 + Paclitaxel 50mg/m2 weekly x 5 (day 1, 8, 15, 22, 29), starting same day as radiotherapy
Esophagectomy performed within 8 weeks after termination of chemoradiotherapy
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.
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).
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.
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.
Esophagectomy only in case of residual or recurrent locoregional cancer.
McGill University Health Centre
Montreal, Quebec, Canada
RECRUITINGCancer Clinical Trials Unit (CCTU) at St. James's Hospital
Dublin, Dublin, Ireland
RECRUITINGOslo universitetssykehus
Oslo, Norway
RECRUITINGUniversitetssykehuset Nord-Norge
Tromsø, Norway
RECRUITINGSt Olavs Hospital
Trondheim, Norway
RECRUITINGLinköpings universitetssjukhus
Linköping, Sweden
RECRUITINGSkånes universitetssjukhus
Lund, Sweden
RECRUITINGÖrebro universitetssjukhus
Örebro, Sweden
RECRUITINGKarolinska University Hospital
Stockholm, Sweden
RECRUITINGNorrlands universitetssjukhus
Umeå, Sweden
RECRUITING...and 2 more locations
Overall survival
When 398 events have occurred
Time frame: 3 years after randomisation
Global Health-related quality of life (HRQOL)
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).
Time frame: 1 year after randomisation
Eating restrictions
EORTC QLQ-OG25 instrument. This instrument consists of 25 items covering upper gastric symptoms or problems in four categories ranging from 1 (Not at all) to 4 (Very much).
Time frame: 1 year after randomisation
Health related quality of life of Cancer patients
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).
Time frame: At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation
Health related quality of life, oesophageal specific.
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).
Time frame: At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation
Health related quality of life, general health
The EuroQoL Group's EQ-5D-5L questionnaire consisting of five dimensions ranging from No problems to Extreme problems or Unable to care.
Time frame: At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation
Event-free survival
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.
Time frame: 5 years after randomisation
Loco-regional and distant relapse rates
Including the relation of relapse location to the radiation field
Time frame: 5 years after randomisation
Histopathological response according to Mandard in operated patients
ypTNM including total and metastatic lymph node count, tumor free resection margins, R0
Time frame: 5 years after randomisation
Health economy
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
Time frame: At baseline and 6, 12, 24, 36 and 60 months after randomisation
Surgical complications
According to the Esophagectomy Complications Consensus Group (ECCG) and classified according to Clavien-Dindo
Time frame: After surgery in operated patients, up to 5 years after randomisation
Treatment-related adverse events and toxicity
NCI-CTCAE Criteria version 5.0
Time frame: Up to 5 years after randomisation
Nutritional outcomes - weight
Weight development. Weight (in kg) will be measured at all visits.
Time frame: Up to 5 years after randomisation
Nutritional outcomes - dysphagia
Dysphagia will be evaluated at all visits according to the CTC adverse event scale, grading from 0 (no problems) to 4 (worst problems).
Time frame: Up to 5 years after randomisation
Gender stratified analyses of all endpoints
Time frame: Up to 5 years after randomisation
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