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

Karolinska University Hospital

Status and phase

Enrolling

Phase 3

Conditions

Esophageal Squamous Cell Carcinoma

Treatments

Procedure: Esophagectomy

Drug: Carboplatin, paclitaxel

Radiation: Neoadjuvant radiotherapy (arm B)

Drug: Cisplatin, paclitaxel

Radiation: Neoadjuvant radiotherapy (arm A)

Drug: Oxaliplatin, calcium folinate, 5-fluorouracil

Study type

Interventional

Funder types

Other

Identifiers

NCT04460352

NEEDS

Details and patient eligibility

About

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.

Enrollment

1,020 estimated patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

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)

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

1,020 participants in 2 patient groups

Control arm (A)

Active Comparator group

Description:

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,

Treatment:

Radiation: Neoadjuvant radiotherapy (arm A)

Drug: Carboplatin, paclitaxel

Procedure: Esophagectomy

Experimental arm (B)

Experimental group

Description:

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.

Treatment:

Drug: Oxaliplatin, calcium folinate, 5-fluorouracil

Drug: Cisplatin, paclitaxel

Drug: Carboplatin, paclitaxel

Radiation: Neoadjuvant radiotherapy (arm B)

Drug: Carboplatin, paclitaxel

Procedure: Esophagectomy