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

October 4, 2023 updated by: Magnus Nilsson, Karolinska University Hospital

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

1020

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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,
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
Other Names:
  • Neoadjuvant chemotherapy
Procedure: Esophagectomy
Esophagectomy performed within 8 weeks after termination of chemoradiotherapy
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).
Other Names:
  • Neoadjuvant Platin-Taxane Regimen (alternative 1)
Procedure: Esophagectomy
Esophagectomy only in case of residual or recurrent locoregional cancer.
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.
Drug: Carboplatin, paclitaxel
Carboplatin AUC 2 + Paclitaxel 50mg/m2 weekly x 5 (day 1, 8, 15, 22, 29), starting same day as radiotherapy
Other Names:
  • Neoadjuvant chemotherapy
Procedure: Esophagectomy
Esophagectomy performed within 8 weeks after termination of chemoradiotherapy
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).
Other Names:
  • Neoadjuvant Platin-Taxane Regimen (alternative 1)
Procedure: Esophagectomy
Esophagectomy only in case of residual or recurrent locoregional cancer.
Radiation: 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.
Drug: 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.
Other Names:
  • Platinum-Fluoropyrimidine Regimens (alternative 2a)
Drug: 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.
Other Names:
  • Platinum-Fluoropyrimidine Regimens (alternative 2b)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Global Health-related quality of life (HRQOL)
Time Frame: 1 year after randomisation
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
Overall survival
Time Frame: 3 years after randomisation
When 398 events have occurred
3 years after randomisation
Eating restrictions
Time Frame: 1 year after randomisation
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Health related quality of life of Cancer patients
Time Frame: At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation
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
Health related quality of life, oesophageal specific.
Time Frame: At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation
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
Health related quality of life, general health
Time Frame: At randomisation but before start of treatment and thereafter 6, 12, 24, 36 and 60 months after randomisation
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
Event-free survival
Time Frame: 5 years after randomisation
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
Loco-regional and distant relapse rates
Time Frame: 5 years after randomisation
Including the relation of relapse location to the radiation field
5 years after randomisation
Histopathological response according to Mandard in operated patients
Time Frame: 5 years after randomisation
ypTNM including total and metastatic lymph node count, tumor free resection margins, R0
5 years after randomisation
Health economy
Time Frame: At baseline and 6, 12, 24, 36 and 60 months after randomisation
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
Surgical complications
Time Frame: After surgery in operated patients, up to 5 years after randomisation
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
Treatment-related adverse events and toxicity
Time Frame: Up to 5 years after randomisation
NCI-CTCAE Criteria version 5.0
Up to 5 years after randomisation
Nutritional outcomes - weight
Time Frame: Up to 5 years after randomisation
Weight development. Weight (in kg) will be measured at all visits.
Up to 5 years after randomisation
Nutritional outcomes - dysphagia
Time Frame: Up to 5 years after randomisation
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
Gender stratified analyses of all endpoints
Time Frame: Up to 5 years after randomisation
Up to 5 years after randomisation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Karolinska University Hospital

Collaborators

The Swedish Research Council
University of Leipzig

Investigators

  • Study Chair: Magnus Nilsson, MD, PhD, Karolinska University Hospital
  • Study Chair: Florian Lordick, MD, PhD, Leipzig University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 27, 2020

Primary Completion (Estimated)

September 18, 2026

Study Completion (Estimated)

December 31, 2031

Study Registration Dates

First Submitted

June 25, 2020

First Submitted That Met QC Criteria

July 1, 2020

First Posted (Actual)

July 7, 2020

Study Record Updates

Last Update Posted (Actual)

October 6, 2023

Last Update Submitted That Met QC Criteria

October 4, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NEEDS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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