Recruiting
Phase 3

Chemoradiotherapy

Sponsor:

Karolinska University Hospital

Code:

NCT04460352

Conditions

Esophageal Squamous Cell Carcinoma

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Neoadjuvant radiotherapy (arm A)

Carboplatin, paclitaxel

Esophagectomy

Neoadjuvant radiotherapy (arm B)

Carboplatin, paclitaxel

Study Details

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.

Conditions

Esophageal Squamous Cell Carcinoma

Study ID

NCT04460352

Start date

Nov 27, 2020

Status verified date

Mar, 2025

Completion date

Dec 31, 2031

Anticipated

Primary completion date

Dec 31, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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)

Study Design

Enrollment

1020 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Control arm (A)

Neoadjuvant chemoradiotherapy followed by esophagectomy.

Radiotherapy: 1.8 Gy fractions 5 days per week in 23 fractions to a total dose of 41.4 Gy.

Chemotherapy: Carboplatin AUC 2 + Paclitaxel 50mg/m2 weekly x 5 (day 1, 8, 15, 22, 29), starting on the first day of radiotherapy.

Esophagectomy: Within 8 weeks of termination of chemoradiotherapy,

experimental: Experimental arm (B)

Definitive chemoradiotherapy followed by surveillance, and esophagectomy only in case of residual or recurrent locoregional cancer.

Radiotherapy: 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.

Chemotherapy: Three alternative regimens:

1. Platin-Taxane Regimen: Carboplatin AUC 2 + Paclitaxel 50mg/m2 on day 1 weekly during the full course of radiotherapy.

2a. Platinum-Fluoropyrimidine Regimen: Cisplatin 75mg/m2 weeks 1 and 5 + 5-fluorouracil 1000 mg/m2/day by continuous infusion weeks 1 and 5.

2b. FOLFOX: Oxaliplatin 85 mg/m2, calcium folinate 200 mg/m2 and 5-fluorouracil 400 mg/m2 weeks 1, 3 and 5 + 5-fluorouracil 800 mg/m2 by continuous infusion weeks 1, 3 and 5.

Interventions

Neoadjuvant radiotherapy (arm A)

1.8 Gy fractions 5 days per week in 23 fractions to a total dose of 41.4 Gy.

Carboplatin, paclitaxel

Carboplatin AUC 2 + Paclitaxel 50mg/m2 weekly x 5 (day 1, 8, 15, 22, 29), starting same day as radiotherapy

Esophagectomy

Esophagectomy performed within 8 weeks after termination of chemoradiotherapy

Neoadjuvant radiotherapy (arm B)

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, 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.

Esophagectomy

Esophagectomy only in case of residual or recurrent locoregional cancer.

Primary outcome measure

  • Overall survival [ Time Frame: 3 years after randomisation ]
  • Global Health-related quality of life (HRQOL) [ Time Frame: 1 year after randomisation ]
  • Eating restrictions [ Time Frame: 1 year after randomisation ]

Central Contacts and Locations

Central contacts

Magnus Nilsson, MD, PhD

+46-707-375186magnus.nilsson@ki.se

Mats Hellström

mats.hellstrom@regionstockholm.se

Locations

McGill University Health Centre

Recruiting

Montréal, Quebec, Canada

Contacts

Mehrnoush Dehgani, PhD

mehrnoush.dehghani@muhc.mcgill.ca

Principal Investigator:

Lorenzo Ferri, MD, PhD

More Information

Sponsor

Karolinska University Hospital

Last update posted

Mar 6, 2025

Last verified

Mar, 2025

Keywords

  • Neoadjuvant chemoradiotherapy
  • Definitive chemoradiotherapy with salvage surgery as needed

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Karolinska University Hospital on 2025-03-06.