Clinical trial NCT04460352: Chemoradiotherapy Followed by Planned Surgery or by Surveillance and Surgery Only When Needed for Oesophageal Cancer
Official title: NEoadjuvant Chemoradiotherapy for Esophageal Squamous Cell Carcinoma Versus Definitive Chemoradiotherapy With Salvage Surgery as Needed (NEEDS Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Esophageal Squamous Cell Carcinoma
Keywords: Neoadjuvant chemoradiotherapy
Definitive chemoradiotherapy with salvage surgery as needed
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
Collaborators: name: University of Leipzig
name: The Swedish Research Council
First posted: 2020-07-07
Enrollment: 1020
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: NEEDS is a pragmatic open-label, randomised, controlled, phase III, multicenter trial with non-inferiority design with regard to the three co-primary endpoints i) Overall survival and superiority for the experimental intervention definitive chemoradiotherapy; ii) Global health related quality of life (HRQOL) one year after randomisation; iii) Eating restictions one year after randomisation.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Overall survival
timeFrame: 3 years after randomisation
measure: Global Health-related quality of life (HRQOL)
timeFrame: 1 year after randomisation
measure: Eating restrictions
timeFrame: 1 year after randomisation
Secondary outcomes:
measure: Health related quality of life of Cancer patients
timeFrame: At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation
measure: Health related quality of life, oesophageal specific.
timeFrame: At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation
measure: Health related quality of life, general health
timeFrame: At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation
measure: Event-free survival
timeFrame: 5 years after randomisation
measure: Loco-regional and distant relapse rates
timeFrame: 5 years after randomisation
measure: Histopathological response according to Mandard in operated patients
timeFrame: 5 years after randomisation
measure: Health economy
timeFrame: At baseline and 6, 12, 24, 36 and 60 months after randomisation
measure: Surgical complications
timeFrame: After surgery in operated patients, up to 5 years after randomisation
measure: Treatment-related adverse events and toxicity
timeFrame: Up to 5 years after randomisation
measure: Nutritional outcomes - weight
timeFrame: Up to 5 years after randomisation
measure: Nutritional outcomes - dysphagia
timeFrame: Up to 5 years after randomisation
measure: Gender stratified analyses of all endpoints
timeFrame: Up to 5 years after randomisation
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Dublin
country: Ireland
facility: Cancer Clinical Trials Unit (CCTU) at St. James's Hospital
city: Oslo
country: Norway
facility: Oslo universitetssykehus
city: Tromsø
country: Norway
facility: Universitetssykehuset Nord-Norge
city: Trondheim
country: Norway
facility: St Olavs Hospital
city: Linköping
country: Sweden
facility: Linköpings universitetssjukhus
city: Lund
country: Sweden
facility: Skånes universitetssjukhus
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Umeå
country: Sweden
facility: Norrlands universitetssjukhus
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset
city: Örebro
country: Sweden
facility: Örebro universitetssjukhus
city: Linkou
country: Taiwan
facility: Chang Gung Memorial Hospital
Study officials:
affiliation: Karolinska University Hospital
name: Magnus Nilsson, MD, PhD
role: STUDY_CHAIR
affiliation: Leipzig University Medical Center
name: Florian Lordick, MD, PhD
role: STUDY_CHAIR
References:
citation: Nilsson M, Olafsdottir H, Alexandersson von Dobeln G, Villegas F, Gagliardi G, Hellstrom M, Wang QL, Johansson H, Gebski V, Hedberg J, Klevebro F, Markar S, Smyth E, Lagergren P, Al-Haidari G, Rekstad LC, Aahlin EK, Wallner B, Edholm D, Johansson J, Szabo E, Reynolds JV, Pramesh CS, Mummudi N, Joshi A, Ferri L, Wong RK, O'Callaghan C, Lukovic J, Chan KK, Leong T, Barbour A, Smithers M, Li Y, Kang X, Kong FM, Chao YK, Crosby T, Bruns C, van Laarhoven H, van Berge Henegouwen M, van Hillegersberg R, Rosati R, Piessen G, de Manzoni G, Lordick F. Neoadjuvant Chemoradiotherapy and Surgery for Esophageal Squamous Cell Carcinoma Versus Definitive Chemoradiotherapy With Salvage Surgery as Needed: The Study Protocol for the Randomized Controlled NEEDS Trial. Front Oncol. 2022 Jul 13;12:917961. doi: 10.3389/fonc.2022.917961. eCollection 2022.