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

NCT04460352 | Recruiting Phase 3 DMC

• 1 other identifier: NEEDS
• Study Type: interventional
• Target: 1,020
• Locations: 5 countries
• Sites: 12

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

Keywords

Neoadjuvant chemoradiotherapy; Definitive chemoradiotherapy with salvage surgery as needed

Outcome Measures

Primary Outcomes (3)

• Overall survival

  When 398 events have occurred

  3 years after randomisation

• 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

• 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 Outcomes (12)

• Health related quality of life of Cancer patients

  At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation

• Health related quality of life, oesophageal specific.

  At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation

• Health related quality of life, general health

  At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation

• Event-free survival

  5 years after randomisation

• Loco-regional and distant relapse rates

  5 years after randomisation

Study Arms (2)

Control arm (A)

ACTIVE COMPARATOR

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,

Radiation: Neoadjuvant radiotherapy (arm A); Drug: Carboplatin, paclitaxel; Procedure: Esophagectomy

Experimental arm (B)

EXPERIMENTAL

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.

Radiation: Neoadjuvant radiotherapy (arm B); Drug: Carboplatin, paclitaxel; Drug: Cisplatin, paclitaxel; Drug: Oxaliplatin, calcium folinate, 5-fluorouracil; Procedure: Esophagectomy

Interventions

Neoadjuvant radiotherapy (arm A) RADIATION

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

Control arm (A)

Carboplatin, paclitaxel DRUG

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

Also known as: Neoadjuvant chemotherapy

Control arm (A)

Esophagectomy PROCEDURE

Esophagectomy performed within 8 weeks after termination of chemoradiotherapy

Control arm (A)

Neoadjuvant radiotherapy (arm B) RADIATION

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.

Experimental arm (B)

Cisplatin, paclitaxel DRUG

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.

Also known as: Platinum-Fluoropyrimidine Regimens (alternative 2a)

Experimental arm (B)

Oxaliplatin, calcium folinate, 5-fluorouracil DRUG

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.

Also known as: Platinum-Fluoropyrimidine Regimens (alternative 2b)

Experimental arm (B)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Karolinska University Hospital: lead
• University of Leipzig: collaborator
• The Swedish Research Council: collaborator

Study Sites (12)

McGill University Health Centre

Montreal, Quebec, Canada

RECRUITING

Cancer Clinical Trials Unit (CCTU) at St. James's Hospital

Dublin, Dublin, D08 NHY1, Ireland

RECRUITING

Oslo universitetssykehus

Oslo, Norway

RECRUITING

Universitetssykehuset Nord-Norge

Tromsø, Norway

RECRUITING

St Olavs Hospital

Trondheim, Norway

RECRUITING

Linköpings universitetssjukhus

Linköping, Sweden

RECRUITING

Skånes universitetssjukhus

Lund, Sweden

RECRUITING

Örebro universitetssjukhus

Örebro, Sweden

RECRUITING

Karolinska University Hospital

Stockholm, Sweden

RECRUITING

Norrlands universitetssjukhus

Umeå, Sweden

RECRUITING

Akademiska sjukhuset

Uppsala, Sweden

RECRUITING

Chang Gung Memorial Hospital

Linkou District, Taiwan

RECRUITING

Related Publications (1)

• 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.

  PMID: 35912196 DERIVED

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

Neoadjuvant Therapy; CP protocol; Esophagectomy; TP protocol; Oxaliplatin; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Digestive System Surgical Procedures; Surgical Procedures, Operative; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Magnus Nilsson, MD, PhD

  Karolinska University Hospital

  STUDY CHAIR

• Florian Lordick, MD, PhD

  Leipzig University Medical Center

  STUDY CHAIR

Central Study Contacts

Magnus Nilsson, MD, PhD

CONTACT

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

Mats Hellström

CONTACT

mats.hellstrom@regionstockholm.se

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: June 25, 2020
• First Posted: July 7, 2020
• Study Start: November 27, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2031
• Last Updated: March 6, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1); IE (1); CA (1); NO (3); SE (6)