Chemoradiotherapy Followed by Planned Surgery or by Surveillance and Surgery Only When Needed for Oesophageal Cancer

Esophageal Squamous Cell Carcinoma Clinical Trial

— NEEDS  

Official title:

NEoadjuvant Chemoradiotherapy for Esophageal Squamous Cell Carcinoma Versus Definitive Chemoradiotherapy With Salvage Surgery as Needed (NEEDS Trial)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04460352
• Other study ID #: NEEDS
• Status: Recruiting
• Phase: Phase 3
• Start date: November 27, 2020
• Est. completion date: December 31, 2031

Study information

• Verified date: October 2023
• Source: Karolinska University Hospital
• Contact: Magnus Nilsson, MD, PhD
• Phone: +46-707-375186
• Email: magnus.nilsson[@]ki.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1020
• Est. completion date: December 31, 2031
• Est. primary completion date: September 18, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma

Intervention

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

Procedure:
• Esophagectomy
Esophagectomy performed within 8 weeks after termination of chemoradiotherapy

Radiation:
• Neoadjuvant radiotherapy (arm B)
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.

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).
• 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.
• 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.

Procedure:
• Esophagectomy
Esophagectomy only in case of residual or recurrent locoregional cancer.

Locations

Country	Name	City	State
Canada	McGill University Health Centre	Montréal	Quebec
Ireland	Cancer Clinical Trials Unit (CCTU) at St. James's Hospital	Dublin
Norway	Oslo universitetssykehus	Oslo
Norway	Universitetssykehuset Nord-Norge	Tromsø
Norway	St Olavs Hospital	Trondheim
Sweden	Linköpings universitetssjukhus	Linköping
Sweden	Skånes universitetssjukhus	Lund
Sweden	Örebro universitetssjukhus	Örebro
Sweden	Karolinska University Hospital	Stockholm
Sweden	Norrlands universitetssjukhus	Umeå
Sweden	Akademiska sjukhuset	Uppsala

Sponsors (3)

Lead Sponsor	Collaborator
Karolinska University Hospital	The Swedish Research Council, University of Leipzig

Countries where clinical trial is conducted

Canada,  Ireland,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	When 398 events have occurred	3 years after randomisation
Primary	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).	1 year after randomisation
Primary	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).	1 year after randomisation
Secondary	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).	At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation
Secondary	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).	At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation
Secondary	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.	At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation
Secondary	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.	5 years after randomisation
Secondary	Loco-regional and distant relapse rates	Including the relation of relapse location to the radiation field	5 years after randomisation
Secondary	Histopathological response according to Mandard in operated patients	ypTNM including total and metastatic lymph node count, tumor free resection margins, R0	5 years after randomisation
Secondary	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	At baseline and 6, 12, 24, 36 and 60 months after randomisation
Secondary	Surgical complications	According to the Esophagectomy Complications Consensus Group (ECCG) and classified according to Clavien-Dindo	After surgery in operated patients, up to 5 years after randomisation
Secondary	Treatment-related adverse events and toxicity	NCI-CTCAE Criteria version 5.0	Up to 5 years after randomisation
Secondary	Nutritional outcomes - weight	Weight development. Weight (in kg) will be measured at all visits.	Up to 5 years after randomisation
Secondary	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).	Up to 5 years after randomisation
Secondary	Gender stratified analyses of all endpoints		Up to 5 years after randomisation