Resectable locally advanced squamous cell carcinoma (SCC) of the esophagus MedDRA version: 21.1 Level: LLT Classification code 10025899 Term: Malignant neoplasm of esophagus System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10025901 Term: Malignant neoplasm of esophagus, unspecified System Organ Class: 100000004864
Conditions
Sponsors
Karolinska University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Histopathologically confirmed SCC of the esophagus in locally advanced stages cT1 N+ or cT2-4a any N, M0 • Technically resectable disease according to the local multidisciplinary team conference (MDT)/tumor board • Age = 18 years and = 80 years. • Performance status ECOG 0-1. • Adequate organ function • Women of childbearing potential 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 • Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment • Written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 480 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 612
Exclusion criteria
Exclusion criteria: • Distant metastases • cT4b • Primary tumor not resectable without laryngectomy. • Impaired renal, hepatic, cardiac, pulmonary or endocrine status • Subjects not considered likely to tolerate multimodality treatment with chemoradiotherapy followed by esophagectomy. • Subjects with previous malignancies • 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The NEEDS trial has three co-primary objectives. First of all to demonstrate that dCRT with salvage esophagectomy as needed, is non-inferior to nCRT followed by surgery, regarding overall survival in patients with operable, locally advanced esophageal squamous cell carcinoma. A second co-primary objective, to be tested only if overall survival non-inferiority has been shown, is to determine the impact on HRQOL of each intervention aiming to show superiority, with regard to Global HRQOL, for dCRT with surgery only when needed, one year after randomization. A third co-primary objective, to be tested for superiority only if overall survival is non-inferior and Global HRQOL is superior, is eating restrictions.;Secondary Objective: • To study prespecified HRQOL endpoints relevant to esophageal cancer and effects of treatment for this disease, repeatedly during treatment and survivorship. • To determine event free survival, loco-regional and distal relapse rates and histological chemoradiotherapy response in the surgical specimen in the control arm. • To investigate the overall health economic impact of each intervention. • To investigate the impact on nutritional status of each intervention during follow-up. • To investigate if there are any gender differences in any of the endpoints. • To exploratively analyse putative tissue and liquid biomarkers for response to the different treatment strategies and long-term benefit.;Primary end point(s): • The first co-primary endpoint of the NEEDS trial is overall survival (OS) with a minimum follow-up of 3 years, with a non-inferiority hypothesis for the experimental intervention dCRT with surveillance and salvage surgery only as needed, compared to the the control intervention nCRT with planned surgery. • A second co-primary endpoint is Global HRQOL one year after randomisation, using the EORTC QLQ-C30 instrument, which will be tested for superiority for the experimental intervention only if non-inferiority for | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • HRQOL will be assessed at baseline, meaning after inclusion and signing of the patient consent form but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation. Specific, predefined quality of life endpoints of particular interest, beside the co-primary endpoints mentioned above, will be Global HRQOL, QLQ- C30 summary score, physical function, dyspnea, diarrhea, dysphagia and anxiety at all time-points mentioned above. • Event free survival (EFS), defined as time to relapse, initiation of any anti-tumor therapy beyond the study treatments, or death, whichever comes first • Loco-regional and distant relapse rates, including the relation of relapse location to the radiation field (in-field or out-field). • Histopathological response • Health economy will be assessed including patient-level medical resource use and societal costs due to sick-leave and other non-medical costs • Surgical complications • Treatment-related adverse events and toxicity • Nutritional outcomes • Gender stratified analyses of all endpoints • Exploratory analyses for putative tissue and liquid biomarkers for response ;Timepoint(s) of evaluation of this end point: 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54 and 60 months after surgery | — |
Countries
Australia, Belgium, Canada, France, Germany, India, Ireland, Norway, Sweden
Contacts
Public ContactTheme Cancer, Upper Adbomen
Karolinska University Hospital
Outcome results
None listed