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

Primary Purpose

Esophageal Squamous Cell Carcinoma

Status

Recruiting

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Neoadjuvant radiotherapy (arm A)

Carboplatin, paclitaxel

Esophagectomy

Neoadjuvant radiotherapy (arm B)

Carboplatin, paclitaxel

Cisplatin, paclitaxel

Oxaliplatin, calcium folinate, 5-fluorouracil

Esophagectomy

About this trial

This is an interventional treatment trial for Esophageal Squamous Cell Carcinoma focused on measuring Neoadjuvant chemoradiotherapy, Definitive chemoradiotherapy with salvage surgery as needed

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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)

Sites / Locations

McGill University Health CentreRecruiting
Cancer Clinical Trials Unit (CCTU) at St. James's HospitalRecruiting
Oslo universitetssykehusRecruiting
Universitetssykehuset Nord-NorgeRecruiting
St Olavs HospitalRecruiting
Linköpings universitetssjukhusRecruiting
Skånes universitetssjukhusRecruiting
Karolinska University HospitalRecruiting
Norrlands universitetssjukhusRecruiting
Akademiska sjukhusetRecruiting
Örebro universitetssjukhusRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Control arm (A)

Experimental arm (B)

Arm 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,

Definitive chemoradiotherapy followed by surveillance, and esophagectomy only in case of residual or recurrent locoregional cancer. Radiotherapy: Two alternative schemes: 1.8 Gy fractions five days per week in 28 fractions to a total dose of 50.4 Gy. 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.

Outcomes

Primary Outcome Measures

Overall survival

When 398 events have occurred

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).

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).

Secondary Outcome Measures

Health related quality of life of Cancer patients

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).

Health related quality of life, oesophageal specific.

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).

Health related quality of life, general health

The EuroQoL Group's EQ-5D-5L questionnaire consisting of five dimensions ranging from No problems to Extreme problems or Unable to care.

Event-free survival

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.

Loco-regional and distant relapse rates

Including the relation of relapse location to the radiation field

Histopathological response according to Mandard in operated patients

ypTNM including total and metastatic lymph node count, tumor free resection margins, R0

Health economy

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

Surgical complications

According to the Esophagectomy Complications Consensus Group (ECCG) and classified according to Clavien-Dindo

Treatment-related adverse events and toxicity

NCI-CTCAE Criteria version 5.0

Nutritional outcomes - weight

Weight development. Weight (in kg) will be measured at all visits.

Nutritional outcomes - dysphagia

Dysphagia will be evaluated at all visits according to the CTC adverse event scale, grading from 0 (no problems) to 4 (worst problems).

Gender stratified analyses of all endpoints

Full Information

NCT ID

NCT04460352

First Posted

June 25, 2020

Last Updated

October 4, 2023

Sponsor

Karolinska University Hospital

Collaborators

University of Leipzig, The Swedish Research Council

1. Study Identification

Unique Protocol Identification Number

NCT04460352

Brief Title

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

Acronym

NEEDS

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 27, 2020 (Actual)

Primary Completion Date

September 18, 2026 (Anticipated)

Study Completion Date

December 31, 2031 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Karolinska University Hospital

Collaborators

University of Leipzig, The Swedish Research Council

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Esophageal Squamous Cell Carcinoma

Keywords

Neoadjuvant chemoradiotherapy, Definitive chemoradiotherapy with salvage surgery as needed

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Model Description

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.

Masking

None (Open Label)

Allocation

Randomized

Enrollment

1020 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Control arm (A)

Arm Type

Active Comparator

Arm Description

Arm Title

Experimental arm (B)

Arm Type

Experimental

Arm Description

Intervention Type

Radiation

Intervention Name(s)

Neoadjuvant radiotherapy (arm A)

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Carboplatin, paclitaxel

Other Intervention Name(s)

Neoadjuvant chemotherapy

Intervention Description

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

Intervention Type

Procedure

Intervention Name(s)

Esophagectomy

Intervention Description

Esophagectomy performed within 8 weeks after termination of chemoradiotherapy

Intervention Type

Radiation

Intervention Name(s)

Neoadjuvant radiotherapy (arm B)

Intervention Description

Two alternative schemes: 1.8 Gy fractions five days per week in 28 fractions to a total dose of 50.4 Gy. 2.0 Gy fractions five days per week in 25 fractions to a total dose of 50 Gy.

Intervention Type

Drug

Intervention Name(s)

Carboplatin, paclitaxel

Other Intervention Name(s)

Neoadjuvant Platin-Taxane Regimen (alternative 1)

Intervention Description

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).

Intervention Type

Drug

Intervention Name(s)

Cisplatin, paclitaxel

Other Intervention Name(s)

Platinum-Fluoropyrimidine Regimens (alternative 2a)

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Oxaliplatin, calcium folinate, 5-fluorouracil

Other Intervention Name(s)

Platinum-Fluoropyrimidine Regimens (alternative 2b)

Intervention Description

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.

Intervention Type

Procedure

Intervention Name(s)

Esophagectomy

Intervention Description

Esophagectomy only in case of residual or recurrent locoregional cancer.

Primary Outcome Measure Information:

Title

Overall survival

Description

When 398 events have occurred

Time Frame

3 years after randomisation

Title

Global Health-related quality of life (HRQOL)

Description

Time Frame

1 year after randomisation

Title

Eating restrictions

Description

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).

Time Frame

1 year after randomisation

Secondary Outcome Measure Information:

Title

Health related quality of life of Cancer patients

Description

Time Frame

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

Title

Health related quality of life, oesophageal specific.

Description

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).

Time Frame

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

Title

Health related quality of life, general health

Description

The EuroQoL Group's EQ-5D-5L questionnaire consisting of five dimensions ranging from No problems to Extreme problems or Unable to care.

Time Frame

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

Title

Event-free survival

Description

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.

Time Frame

5 years after randomisation

Title

Loco-regional and distant relapse rates

Description

Including the relation of relapse location to the radiation field

Time Frame

5 years after randomisation

Title

Histopathological response according to Mandard in operated patients

Description

ypTNM including total and metastatic lymph node count, tumor free resection margins, R0

Time Frame

5 years after randomisation

Title

Health economy

Description

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

Time Frame

At baseline and 6, 12, 24, 36 and 60 months after randomisation

Title

Surgical complications

Description

According to the Esophagectomy Complications Consensus Group (ECCG) and classified according to Clavien-Dindo

Time Frame

After surgery in operated patients, up to 5 years after randomisation

Title

Treatment-related adverse events and toxicity

Description

NCI-CTCAE Criteria version 5.0

Time Frame

Up to 5 years after randomisation

Title

Nutritional outcomes - weight

Description

Weight development. Weight (in kg) will be measured at all visits.

Time Frame

Up to 5 years after randomisation

Title

Nutritional outcomes - dysphagia

Description

Dysphagia will be evaluated at all visits according to the CTC adverse event scale, grading from 0 (no problems) to 4 (worst problems).

Time Frame

Up to 5 years after randomisation

Title

Gender stratified analyses of all endpoints

Time Frame

Up to 5 years after randomisation

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Magnus Nilsson, MD, PhD

Phone

+46-707-375186

magnus.nilsson@ki.se

First Name & Middle Initial & Last Name or Official Title & Degree

Mats Hellström

Phone

+46-8-51773677

mats.hellstrom@sll.se

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Magnus Nilsson, MD, PhD

Organizational Affiliation

Karolinska University Hospital

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Florian Lordick, MD, PhD

Organizational Affiliation

Leipzig University Medical Center

Official's Role

Study Chair

Facility Information:

Facility Name

McGill University Health Centre

City

Montréal

State/Province

Quebec

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Mehrnoush Dehgani, PhD

mehrnoush.dehghani@muhc.mcgill.ca

First Name & Middle Initial & Last Name & Degree

Lorenzo Ferri, MD, PhD

Facility Name

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

City

Dublin

ZIP/Postal Code

D08 NHY1

Country

Ireland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ingrid Kiernan

Phone

+353 1 4103754

cancerclinicaltrials@stjames.ie

First Name & Middle Initial & Last Name & Degree

John Reynolds, Prof

First Name & Middle Initial & Last Name & Degree

Grainne O'Kane, Dr

First Name & Middle Initial & Last Name & Degree

Moya Cunningham, Dr

Facility Name

Oslo universitetssykehus

City

Oslo

Country

Norway

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Janne Christoffersen, RN

jannec@ous-hf.no

First Name & Middle Initial & Last Name & Degree

Ghazwan Al-Haidari, MD, PhD

Facility Name

Universitetssykehuset Nord-Norge

City

Tromsø

Country

Norway

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Eirik Kjus Aahlin, MD, PhD

eirik.kjus.aahlin@unn.no

First Name & Middle Initial & Last Name & Degree

Kristin Woll, RN

kristin.woll@unn.no

First Name & Middle Initial & Last Name & Degree

Eirik Kjus Aahlin, MD, PhD

Facility Name

St Olavs Hospital

City

Trondheim

Country

Norway

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Marte Romundstad, RN

marte.romunstad@stolav.no

First Name & Middle Initial & Last Name & Degree

Lars Cato Rekstad, MD, PhD

Facility Name

Linköpings universitetssjukhus

City

Linköping

Country

Sweden

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

David Edholm, MD

david.edholm@regionostergotland.se

First Name & Middle Initial & Last Name & Degree

Anna Lindhoff Larsson, RN

anna.lindhoff.larsson@regionostergotland.se

Facility Name

Skånes universitetssjukhus

City

Lund

Country

Sweden

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Monika Meszaros, RN

monika.meszaros@skane.se

First Name & Middle Initial & Last Name & Degree

Marit Bakos, RN

marit.bakos@skane.se

First Name & Middle Initial & Last Name & Degree

Jan Johansson, MD, PhD

Facility Name

Karolinska University Hospital

City

Stockholm

Country

Sweden

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Berit Sunde, RN, PhD

berit.sunde@ki.se

First Name & Middle Initial & Last Name & Degree

Maria Lampi, RN

maria.lampi@regionstockholm.se

First Name & Middle Initial & Last Name & Degree

Magnus Nilsson, MD, PhD

First Name & Middle Initial & Last Name & Degree

Gabriella Alexandersson von Döbeln, MD, PhD

Facility Name

Norrlands universitetssjukhus

City

Umeå

Country

Sweden

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Birgitta Orrvik Olsson, RN

birgitta.orrvikolsson@regionvasterbotten.se

First Name & Middle Initial & Last Name & Degree

Agneta Karhu, RN

agneta.karhu@regionvasterbotten.se

First Name & Middle Initial & Last Name & Degree

Bengt Wallner, MD, PhD

Facility Name

Akademiska sjukhuset

City

Uppsala

Country

Sweden

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Lena Ekfjord, RN

lena.ekfjord@akademiska.se

First Name & Middle Initial & Last Name & Degree

Jakob Hedberg, MD, PhD

Facility Name

Örebro universitetssjukhus

City

Örebro

Country

Sweden

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Linnea Sundström, RN

linnea.sundstrom@regionorebrolan.se

First Name & Middle Initial & Last Name & Degree

Eva Szabo, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

35912196

Citation

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.

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

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