NEoadjuvant chemoradiotherapy for Esophageal squamous cell carcinoma versus Definitive chemoradiotherapy with salvage Surgery as needed (The NEEDS Trial)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karolinska University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

11 Mar 2020 → ongoing

Decision date (initial)

2025-05-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2022-500966-82-00

EudraCT number

2020-000149-15

ClinicalTrials.gov

NCT04460352

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Others, Safety

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.

Secondary objectives 7

1. To study prespecified HRQOL endpoints relevant to esophageal cancer and effects of treatment for this disease, repeatedly during treatment and survivorship.
2. To determine event free survival, loco-regional and distal relapse rates and histological chemoradiotherapy response in the surgical specimen in the control arm.
3. To investigate the overall health economic impact of each intervention.
4. To investigate the impact on nutritional status of each intervention during follow-up.
5. To investigate whether any of the endpoints are affected by the type of radiological follow-up, CT or PET-CT, in the dCRT with salvage esophagectomy as needed trial arm.
6. To investigate if there are any gender differences in any of the endpoints.
7. To exploratively analyze putative tissue and liquid biomarkers for response to the different treatment strategies and long-term benefit.

Conditions and MedDRA coding

Resectable locally advanced squamous cell carcinoma (SCC) of the esophagus

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Histopathologically confirmed squamous cell carcinoma of the esophagus in locally advanced stages cT1 N+ or cT2-4a any N, M0
2. Technically resectable disease according to the local multidisciplinary team conference (MDT)/tumor board.
3. Performance status ECOG 0-1.
4. Women of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to randomisation.
5. Patients of childbearing/reproductive potential should use highly effective method of birth control measures during the study treatment period and for at least six months after the last study treatment.
6. Before patient registration/randomisation, written informed consent must be given according to ICH/GCP/GDPR and national/local regulations.
7. Age ≥ 18 years and ≤ 80 years.
8. Adequate organ function
9. Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment

Exclusion criteria 9

1. M1 according to current (8th) version of of the AJCC TNM classification.
2. cT4b according to current (8th) version of of the AJCC TNM classification.
3. Primary tumor not resectable without laryngectomy.
4. Impaired renal, hepatic, cardiac, pulmonary or endocrine status that compromises the eligibility of the patient for multimodality treatment with chemoradiotherapy followed by esophagectomy.
5. Subjects with previous malignancies are excluded unless a complete remission or complete resection was achieved at least 5 years prior to study entry.
6. 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.
7. Subjects not considered likely to tolerate multimodality treatment with chemoradiotherapy followed by esophagectomy.
8. Prior or concomitant treatment with radiotherapy or chemoradiotherapy with potential overlap of radiotherapy fields.
9. Known uncontrollable hypersensitivity to the components of the chemotherapeutic agents used in the trial regimens.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Overall survival (OS) with a minimum follow-up of 3 years.
2. Health-related quality of life (HRQOL) one year after randomization

Secondary endpoints 10

1. Event free survival (EFS), defined as 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.
2. Loco-regional and distant relapse rates, including the relation of relapse location to the radiation field.
3. Histopathological response according to Mandard, as well as other pathological data in operated patients, ypTNM including total and metastatic lymph node count, tumour free resection margins, R0.
4. Health economy will be 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, reported at baseline and 6, 12, 24, 36 and 60 months after randomisation.
5. Surgical complications according to the Esophagectomy Complications Consensus Group and classified according to Clavien-Dindo.
6. Treatment-related adverse events and toxicity coded by NCI.CTCAE criteria version 5.0.
7. Nutritional outcomes including weight development, dysphagia and appetite assessment.
8. Gender stratified analyses of all endpoints.
9. Exploratory analyses for putative tissue and liquid biomarkers for response to RCT and benefit from either of the two treatment strategies (optional per center).
10. 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 randomization

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karolinska University Hospital

Sponsor organisation

Karolinska University Hospital

Address

Eugeniavagen 3

City

Solna

Postcode

171 64

Country

Sweden

Scientific contact point

Organisation

Karolinska University Hospital

Contact name

Magnus Nilsson

Public contact point

Organisation

Karolinska University Hospital

Contact name

Magnus Nilsson

Locations

4 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 23 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications