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SCOPE1: a randomised phase II/III multicentre clinical trial of definitive chemoradiation, with or without cetuximab, in carcinoma of the oesophagus.

SCOPE1: a randomised phase II/III multicentre clinical trial of definitive chemoradiation, with or without cetuximab, in carcinoma of the oesophagus.
SCOPE1: a randomised phase II/III multicentre clinical trial of definitive chemoradiation, with or without cetuximab, in carcinoma of the oesophagus.

Background: chemoradiotherapy is the standard of care for patients with oesophageal cancer unsuitable for surgery due to the presence of co-morbidity or extent of disease, and is a standard treatment option for patients with squamous cell carcinoma of the oesophagus. Modern regimens of chemoradiotherapy can lead to significant long-term survival. However the majority of patients will die of their disease, most commonly with local progression/recurrence of their tumours. Cetuximab may overcome one of the principal mechanisms of tumour radio-resistance, namely tumour repopulation, in patients treated with chemoradiotherapy.

The purpose of this research is first to determine whether the addition of cetuximab to definitive chemoradiotherapy for treatment of patients with non-metastatic carcinoma of the oesophagus is active (in terms of failure-free rate), safe, and feasible within the context of a multi-centre randomised controlled trial in the UK. If the first stage is successful then the trial will continue to accrue sufficient patients to establish whether the addition of cetuximab to the standard treatment improves overall survival.


Methods/design: SCOPE1 is a two arm, open, randomised multicentre Phase II/III trial. Eligible patients will have histologically confirmed carcinoma of the oesophagus and have been chosen to receive definitive chemoradiotherapy by an accredited multidisciplinary team including a specialist Upper GI surgeon. 420 patients will be randomised to receive definitive chemoradiotherapy with or without cetuximab using a 1:1 allocation ratio.

During Phase II of the study, the trial will assess safety (toxicity), activity (failure-free rate) and feasibility (recruitment rate and protocol dose modifications/delays) in 90 patients in the experimental arm. If the experimental arm is found to be active, safe, and feasible by the Independent Data Monitoring Committee then recruitment will continue into Phase III. This second stage will recruit a further 120 patients into each arm and compare the overall survival of both groups.

All patients randomised into Phase II will contribute to the Phase III comparison of overall survival. In addition to overall survival, Phase III of the study will also assess toxicity, health related quality of life and cost effectiveness. A detailed radiotherapy protocol and quality assurance procedure has been incorporated into this trial.


Trial registration: ISRCTN: ISRCTN47718479

Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Carcinoma, Squamous Cell, Cetuximab, Chemoradiotherapy, Esophageal Neoplasms, Humans, Receptor, Epidermal Growth Factor, Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
1471-2407
Hurt, Christopher N.
bf8b37a0-8f08-4b47-b3f3-6fc65f7ab87f
Nixon, Lisette S.
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Griffiths, Gareth O.
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Al-Mokhtar, Ruby
675f9c41-d647-4d6e-8b31-44b7cb9c3f09
Gollins, Simon
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Staffurth, John N.
f588d8b9-7bf7-4665-9f2d-5688e4602a8b
Phillips, Ceri J.
7d209a53-2adc-4b5a-9445-266d6d69333c
Blazeby, Jane M.
689d490e-fca3-4430-88de-f19ec6cebf58
Crosby, Tom D.
151efb37-49f4-4d86-bb45-c28a0d3b8614
et al.
Hurt, Christopher N.
bf8b37a0-8f08-4b47-b3f3-6fc65f7ab87f
Nixon, Lisette S.
e39c20b0-200a-49ea-aa3e-fa10c6df7dd8
Griffiths, Gareth O.
7fd300c0-d279-4ff6-842d-aa1f2b9b864d
Al-Mokhtar, Ruby
675f9c41-d647-4d6e-8b31-44b7cb9c3f09
Gollins, Simon
ae092a24-b3fb-4d95-b5af-802a14bd79f8
Staffurth, John N.
f588d8b9-7bf7-4665-9f2d-5688e4602a8b
Phillips, Ceri J.
7d209a53-2adc-4b5a-9445-266d6d69333c
Blazeby, Jane M.
689d490e-fca3-4430-88de-f19ec6cebf58
Crosby, Tom D.
151efb37-49f4-4d86-bb45-c28a0d3b8614

Hurt, Christopher N., Nixon, Lisette S. and Griffiths, Gareth O. , et al. (2011) SCOPE1: a randomised phase II/III multicentre clinical trial of definitive chemoradiation, with or without cetuximab, in carcinoma of the oesophagus. BMC cancer, 11, [466]. (doi:10.1186/1471-2407-11-466).

Record type: Article

Abstract

Background: chemoradiotherapy is the standard of care for patients with oesophageal cancer unsuitable for surgery due to the presence of co-morbidity or extent of disease, and is a standard treatment option for patients with squamous cell carcinoma of the oesophagus. Modern regimens of chemoradiotherapy can lead to significant long-term survival. However the majority of patients will die of their disease, most commonly with local progression/recurrence of their tumours. Cetuximab may overcome one of the principal mechanisms of tumour radio-resistance, namely tumour repopulation, in patients treated with chemoradiotherapy.

The purpose of this research is first to determine whether the addition of cetuximab to definitive chemoradiotherapy for treatment of patients with non-metastatic carcinoma of the oesophagus is active (in terms of failure-free rate), safe, and feasible within the context of a multi-centre randomised controlled trial in the UK. If the first stage is successful then the trial will continue to accrue sufficient patients to establish whether the addition of cetuximab to the standard treatment improves overall survival.


Methods/design: SCOPE1 is a two arm, open, randomised multicentre Phase II/III trial. Eligible patients will have histologically confirmed carcinoma of the oesophagus and have been chosen to receive definitive chemoradiotherapy by an accredited multidisciplinary team including a specialist Upper GI surgeon. 420 patients will be randomised to receive definitive chemoradiotherapy with or without cetuximab using a 1:1 allocation ratio.

During Phase II of the study, the trial will assess safety (toxicity), activity (failure-free rate) and feasibility (recruitment rate and protocol dose modifications/delays) in 90 patients in the experimental arm. If the experimental arm is found to be active, safe, and feasible by the Independent Data Monitoring Committee then recruitment will continue into Phase III. This second stage will recruit a further 120 patients into each arm and compare the overall survival of both groups.

All patients randomised into Phase II will contribute to the Phase III comparison of overall survival. In addition to overall survival, Phase III of the study will also assess toxicity, health related quality of life and cost effectiveness. A detailed radiotherapy protocol and quality assurance procedure has been incorporated into this trial.


Trial registration: ISRCTN: ISRCTN47718479

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1471-2407-11-466 - Version of Record
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Accepted/In Press date: 28 October 2011
e-pub ahead of print date: 28 October 2011
Keywords: Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Carcinoma, Squamous Cell, Cetuximab, Chemoradiotherapy, Esophageal Neoplasms, Humans, Receptor, Epidermal Growth Factor, Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
Organisations: Clinical Trials Unit

Identifiers

Local EPrints ID: 406310
URI: http://eprints.soton.ac.uk/id/eprint/406310
ISSN: 1471-2407
PURE UUID: c1e52a71-6df3-4e3c-9198-edcbb95082ae
ORCID for Christopher N. Hurt: ORCID iD orcid.org/0000-0003-1206-8355
ORCID for Gareth O. Griffiths: ORCID iD orcid.org/0000-0002-9579-8021

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Date deposited: 10 Mar 2017 10:44
Last modified: 21 Mar 2024 03:14

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Contributors

Author: Christopher N. Hurt ORCID iD
Author: Lisette S. Nixon
Author: Ruby Al-Mokhtar
Author: Simon Gollins
Author: John N. Staffurth
Author: Ceri J. Phillips
Author: Jane M. Blazeby
Author: Tom D. Crosby
Corporate Author: et al.

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