Study of Chemoradiotherapy in Oesophageal Cancer Including PET Response and Dose Escalation

NCT02741856 | Unknown Phase 2 DMC

• 3 other identifiers: 2014/VCC/00152015-001740-11Ethics Reference Number
• Study Type: interventional
• Target: 584
• Locations: 1 country
• Sites: 26

Brief Summary

Research has shown that increasing the dose of radiotherapy improves outcomes in patients with lung and head and neck cancers. This study aims to see whether this is also the case for patients with tumour of the oesophagus. This trial will compare the effects of the standard dose of radiotherapy to a higher dose whilst closely monitoring the side effects. A comparison will also be made regarding the effects of the standard drugs used in chemotherapy (cisplatin and capecitabine) with an alternative combination (carboplatin and paclitaxel) in patients that do not show a response to chemotherapy with standard drugs early on in treatment. All patients will receive 6 weeks of chemotherapy and 5 weeks of chemoradiotherapy. How the study will be conducted: Prior to the commencement of treatment each patient will have a special scan called a PET scan. Patients will receive a second PET scan two weeks after the start of standard chemotherapy. The changes between the two scans will then be used to allocate treatment into the different arms of the study. All study subjects will be randomised to receive either the standard radiotherapy dose or the high radiotherapy dose. The participants that do not respond to the first cycle of standard chemotherapy will be eligible to take part in the aspect of the trial looking at an alternative chemotherapy regimen. Patients will be randomised as follows; On the basis of the second PET scan, patients who are not responding to standard chemotherapy will be allocated by a computer to one of the four groups detailed below:

• Standard chemotherapy and standard dose of radiotherapy
• Standard chemotherapy and higher dose of radiotherapy
• Alternative chemotherapy and standard dose of radiotherapy
• Alternative chemotherapy and higher dose of radiotherapy Patients who are responding to standard chemotherapy (or where the response is unknown or those who were not eligible for PET scan portion of the study) will be allocated by a computer to one of two groups detailed below:
• Standard chemotherapy and standard dose of radiotherapy
• Standard chemotherapy and higher dose of radiotherapy The arms within each of the groups above (responders and non-responders) will be equal in size and patients will be allocated randomly by a computer. This study will also compare the way that this treatment affects the two different cell types found in oesophageal tumours. The effects of the different treatment, together with the costs of the different treatment and the effects on quality of life will be analysed to see which is more effective for each of the different groups.

Conditions

Oesophageal Cancer

Outcome Measures

Primary Outcomes (5)

• Primary endpoint phase II in squamous cell carcinoma comparing standard dose radiotherapy to high dose radiotherapy

  24 week treatment failure free survival (TFFS).

  24 weeks

• Primary endpoint phase III in squamous cell carcinoma: Overall survival (OS) comparing standard dose radiotherapy to high dose radiotherapy

  Overall survival (OS)

  24 weeks

• Primary endpoint in squamous cell carcinoma when switching chemotherapy

  24 week treatment failure free survival (TFFS).

  24 weeks

• Primary endpoint phase in adenocarcinoma phase II comparing standard dose radiotherapy to high dose radiotherapy

  24 week treatment failure free survival (TFFS).

  24 weeks

• Primary endpoint in adenocarcinoma when switching chemotherapy

  24 week treatment failure free survival (TFFS).

  24 weeks

Secondary Outcomes (5)

• Overall survival

  5 years follow up

• Progression free survival

  5 years

• Quality of Life

  Baseline, week 7, end of treatment, 6, 12 and 24 months

• Toxicity

  After each treatment cycle and at follow up visits

• Health economics

  Baseline, end of treatment, 6, 12 and 24 months

Study Arms (4)

Arm 1 (carboplatin/paclitaxel+standard RT dose)

EXPERIMENTAL

Cycle 1: Week 1-3: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21 Cycle 2: Week 4-6: carboplatin AUC 5 on D1 and paclitaxel 175mg/m2 on D1 Week 7-11: Weekly carboplatin AUC 2 and paclitaxel 50mg/m2 concomitant with radiotherapy (50Gy/25 fractions)

Drug: Carboplatin; Drug: Paclitaxel; Drug: Cisplatin; Drug: Capecitabine; Radiation: Radiotherapy

Arm 2 (cisplatin/capecitabine+standard RT dose)

EXPERIMENTAL

Cycle 1: Week 1-3: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21 Cycle 2: Week 4-6: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21 Cycle 3: Week 7-9: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21 Cycle 4: Week 10-11: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-14 Cycles 3 and 4 are given concomitantly with radiotherapy (50Gy/25 fractions). Capecitabine stops on last day of RT.

Drug: Cisplatin; Drug: Capecitabine; Radiation: Radiotherapy

Arm 3 (carboplatin/paclitaxel+high RT dose)

EXPERIMENTAL

Cycle 1: Week 1-3: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21 Cycle 2: Week 4-6: carboplatin AUC 5 on D1 and paclitaxel 175mg/m2 on D1 Week 7-11: Weekly carboplatin AUC 2 and paclitaxel 50mg/m2 concomitant with radiotherapy (60Gy/25 fractions)

Drug: Carboplatin; Drug: Paclitaxel; Drug: Cisplatin; Drug: Capecitabine; Radiation: Radiotherapy

Arm 4 (Cisplatin+Capecitabine+high RT dose)

EXPERIMENTAL

Cycle 1: Week 1-3: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21 Cycle 2: Week 4-6: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21 Cycle 3: Week 7-9: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-21 Cycle 4: Week 10-11: cisplatin 60mg/m2 on D1 and capecitabine 625mg/m2 bd D1-14 Cycles 3 and 4 are given concomitantly with radiotherapy (60Gy/25 fractions). Capecitabine stops on last day of RT.

Drug: Cisplatin; Drug: Capecitabine; Radiation: Radiotherapy

Interventions

Carboplatin DRUG

For more information please see the arm descriptions section.

Arm 1 (carboplatin/paclitaxel+standard RT dose); Arm 3 (carboplatin/paclitaxel+high RT dose)

Paclitaxel DRUG

For more information please see the arm descriptions section.

Arm 1 (carboplatin/paclitaxel+standard RT dose); Arm 3 (carboplatin/paclitaxel+high RT dose)

Cisplatin DRUG

For more information please see the arm descriptions section.

Arm 1 (carboplatin/paclitaxel+standard RT dose); Arm 2 (cisplatin/capecitabine+standard RT dose); Arm 3 (carboplatin/paclitaxel+high RT dose); Arm 4 (Cisplatin+Capecitabine+high RT dose)

Capecitabine DRUG

For more information please see the arm descriptions section.

Arm 1 (carboplatin/paclitaxel+standard RT dose); Arm 2 (cisplatin/capecitabine+standard RT dose); Arm 3 (carboplatin/paclitaxel+high RT dose); Arm 4 (Cisplatin+Capecitabine+high RT dose)

Radiotherapy RADIATION

For more information please see the arm descriptions section.

Arm 1 (carboplatin/paclitaxel+standard RT dose); Arm 2 (cisplatin/capecitabine+standard RT dose); Arm 3 (carboplatin/paclitaxel+high RT dose); Arm 4 (Cisplatin+Capecitabine+high RT dose)

Eligibility Criteria

• Age: 17 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older.
• Have been selected to receive potentially curative definitive chemoradiotherapy by a specialist Upper GI MDT.
• Histologically confirmed adenocarcinoma, undifferentiated cancer or squamous cell carcinoma.
• Tumours of the cervical, thoracic oesophagus, or gastro-oesophageal junction (GOJ) with proximal extent of disease no more proximal than 15cm ab oral and distal extent of primary tumour no more than 2 cm beyond the GOJ.
• Tumours staged with endoscopic ultrasound\*, CT and PET-CT to be T1-4 and N+/- (provided total tumour length including nodes is ≤10).
• Total contiguous disease length ≤10cm defined by CT, EUS and/or PET. The primary tumour should also be ≤8cm.
• WHO performance status 0 or 1.
• Adequate cardiovascular function for safe delivery of chemo-radiation in the opinion of the principal investigator. Where there is clinical concern patients should have an adequate cardiac ejection fraction ≥ 40% as determined by MUGA scan or ECHO (within 4 weeks prior to enrolment).
• Adequate respiratory function for safe delivery of chemo-radiation in the opinion of the Principal Investigator. Where there is clinical concern FEV1 ≥ 1 litre as determined by spirometry (within 4 weeks prior to enrolment).
• Patients with clinically significant hearing impairment (hearing loss with hearing aid, or hearing loss where intervention indicated, or limiting daily activities or tinnitus limiting daily activities or sensory-motor neuropathy are eligible, however, cisplatin will be replaced by carboplatin (AUC 5)
• Adequate haematological, hepatic and renal function
• Patients agree to use effective forms of contraception during the trial (if applicable to patient).
• Patients who have provided written informed consent prior to enrolment.
• Baseline SUVmax ≥ 5.
• PET scan 14 days after start of chemo (-2/+3 days from this date is acceptable)

You may not qualify if:

• Patients who have had previous treatment for invasive oesophageal carcinoma or gastro-oesophageal junction carcinoma (not including PDT or laser therapy for high grade dysplasia/carcinoma in-situ).
• Patients with metastatic disease i.e. M1a or M1b according to UICC TNM version 7.
• Patients with other active malignancy or past malignancy in remission for less than 3 years are not eligible for the trial. However, patients with the following conditions which have been curatively treated will NOT be excluded: basal cell carcinoma, carcinoma-in-situ breast and carcinoma-in-situ cervix.
• Patients with \>2cm mucosal extension of tumour into the stomach or where the superior extent is proximal to 15 cm ab oral.
• Patients with unstable angina or uncontrolled hypertension or cardiac failure or other clinically significant cardiac disease.
• Patients who need continued treatment with a contraindicated concomitant medication or therapy.
• Patients with known dihydropyrimidine dehydrogenase (DPD) deficiency.
• \. Patients with serious infections
• \. Known hypersensitivity to IMPs.
• \. Women who are pregnant or breastfeeding.
• \. Oesophageal stent (patients requiring a PEG/RIG/feeding jejunostomy for nutritional purposes are eligible).
• \. Any other situation, which in the opinion of the local PI, makes the patient an unsuitable candidate for this trial.

Sponsors & Collaborators

• Lisette Nixon: lead
• Cancer Research UK: collaborator

Study Sites (26)

Aberdeen Royal Infirmary

Aberdeen, United Kingdom

RECRUITING

Bristol Haematology & Oncology

Bristol, United Kingdom

RECRUITING

Addenbrooke's Hospital

Cambridge, United Kingdom

RECRUITING

Kent and Canterbury

Canterbury, United Kingdom

NOT YET RECRUITING

Velindre Cancer Care Centre

Cardiff, CF14 2TL, United Kingdom

RECRUITING

Cheltenham General Hospital

Cheltenham, United Kingdom

RECRUITING

University Hospital Coventry

Coventry, United Kingdom

RECRUITING

Derby Teaching Hospitals NHS Trust

Derby, United Kingdom

RECRUITING

Glan Clwyd Hospital

Glan Clwyd, United Kingdom

RECRUITING

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom

RECRUITING

Gloucestershire Royal Hospital

Gloucester, United Kingdom

RECRUITING

Castle Hill Hospital

Hull, United Kingdom

RECRUITING

The Clatterbridge Cancer Centre nhs Foundation Trust

Liverpool, United Kingdom

RECRUITING

Guy's and St Thomas'

London, United Kingdom

RECRUITING

Imperial College Healthcare NHS Trust

London, United Kingdom

RECRUITING

North Middlesex Hospital

London, United Kingdom

RECRUITING

The Royal Marsden Hospitals (Fulham)

London, United Kingdom

RECRUITING

The James Cook University Hospital

Middlesbrough, United Kingdom

RECRUITING

Churchill Hospital

Oxford, United Kingdom

RECRUITING

Peterborough and Stamford Hospitals NHS Foundation Trust

Peterborough, United Kingdom

RECRUITING

Sheffield Teaching Hospitals - Weston Park Hospital

Sheffield, United Kingdom

RECRUITING

University Hospital Southampton NHS Foundation Trust

Southampton, United Kingdom

RECRUITING

The Royal Marsden Hospitals (Sutton, Surrey)

Sutton, United Kingdom

RECRUITING

Singleton Hospital

Swansea, United Kingdom

RECRUITING

Worcestershire Royal Hospital

Worcester, United Kingdom

RECRUITING

Wrexham Maelor

Wrexham, United Kingdom

RECRUITING

Related Publications (4)

• Holland-Hart D, Longo M, Bridges S, Nixon L, Hawkins M, Crosby T, Nelson A. A qualitative study exploring participants' experiences of the SCOPE2 trial: chemoradiotherapy dose escalation in oesophageal cancer. Trials. 2025 Feb 26;26(1):70. doi: 10.1186/s13063-025-08768-z.

  PMID: 40012034 DERIVED

• Holland-Hart D, Longo M, Bridges S, Nixon LS, Hawkins M, Crosby T, Nelson A. The experiences of patients with oesophageal cancer receiving chemoradiotherapy treatment: a qualitative study embedded in the SCOPE2 trial. BMJ Open. 2024 Sep 23;14(9):e076394. doi: 10.1136/bmjopen-2023-076394.

  PMID: 39313288 DERIVED

• Mukherjee S, Hurt CN, Adams R, Bateman A, Bradley KM, Bridges S, Falk S, Griffiths G, Gwynne S, Jones CM, Markham PJ, Maughan T, Nixon LS, Radhakrishna G, Roy R, Schoenbuchner S, Sheikh H, Spezi E, Hawkins M, Crosby TDL. Efficacy of early PET-CT directed switch to carboplatin and paclitaxel based definitive chemoradiotherapy in patients with oesophageal cancer who have a poor early response to induction cisplatin and capecitabine in the UK: a multi-centre randomised controlled phase II trial. EClinicalMedicine. 2023 Jun 26;61:102059. doi: 10.1016/j.eclinm.2023.102059. eCollection 2023 Jul.

  PMID: 37409323 DERIVED

• Sakanaka K, Ishida Y, Fujii K, Ishihara Y, Nakamura M, Hiraoka M, Mizowaki T. Radiation Dose-escalated Chemoradiotherapy Using Simultaneous Integrated Boost Intensity-Modulated Radiotherapy for Locally Advanced Unresectable Thoracic Oesophageal Squamous Cell Carcinoma: A Single-institution Phase I Study. Clin Oncol (R Coll Radiol). 2021 Mar;33(3):191-201. doi: 10.1016/j.clon.2020.07.012. Epub 2020 Aug 4.

  PMID: 32768158 DERIVED

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

Carboplatin; Paclitaxel; Cisplatin; Capecitabine; Radiotherapy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Therapeutics

Study Officials

• Tom Crosby

  Velindre University NHS Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah Bridges

CONTACT

+44 2920 687869; scope2@cardiff.ac.uk

Lisette Nixon, PhD

CONTACT

+44 2920687459; nixonls@cardiff.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior Trial Manager

Study Record Dates

• First Submitted: April 12, 2016
• First Posted: April 18, 2016
• Study Start: November 4, 2016
• Primary Completion: April 1, 2021
• Study Completion: April 1, 2023
• Last Updated: October 25, 2018

Record last verified: 2018-10

Locations

GB (26)