The SCOPE 2 Trial: Study of chemoradiotherapy in oesophageal cancer including PET response and dose escalation
| ISRCTN | ISRCTN97125464 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN97125464 |
| EudraCT/CTIS number | 2015-001740-11 |
| IRAS number | 169633 |
| ClinicalTrials.gov number | NCT02741856 |
| Secondary identifying numbers | 20358, IRAS 169633 |
- Submission date
- 12/09/2016
- Registration date
- 26/10/2016
- Last edited
- 05/03/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Contact information
Dr Sarah Bridges
Public
Public
-
-
-
United Kingdom
 ORCID ID |
0000-0002-8189-2930 |
|---|---|
| Phone | +44 2920 6 87869 |
| scope2@cardiff.ac.uk |
Dr Chris Hurt
Scientific
Scientific
-
-
-
United Kingdom
| ORCID ID |
0000-0003-1206-8355 |
|---|---|
| Phone | +44 2920 6 87869 |
| scope2@cardiff.ac.uk |
Study information
| Study design | Factorial open-label randomised parallel phase II/III trial with embedded factorial open-label randomised parallel phase II trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | A randomised Phase II/III trial to study radiotherapy dose escalation in patients with oesophageal cancer treated with definitive chemoradiation with an embedded Phase II trial for patients with a poor early response using positron emission tomography (PET) |
| Study acronym | SCOPE2 |
| Study objectives | Phase II/III trial: The aim of this study is to evaluate whether increasing the dose of radiotherapy improves outcomes in patients with tumour of the oesophagus. Embedded Phase II trial: The aim of this study is to compare 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. |
| Ethics approval(s) | National Institute for Social Care and Health Research Research Ethics Committee, 22/01/2016, ref: 15/WA/0392 |
| Health condition(s) or problem(s) studied | Oesophageal cancer |
| Intervention | Prior to the commencement of treatment each patient will have a PET scan. Consenting 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. 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: Experimental: Arm 1 (carboplatin/paclitaxel+standard RT dose) 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) Interventions: Drug: Carboplatin Drug: Paclitaxel Drug: Cisplatin Drug: Capecitabine Radiation: Radiotherapy Experimental: Arm 2 (cisplatin/capecitabine+standard RT dose) 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 D1-12 Cycles 3 and 4 are given concomitantly with radiotherapy (50Gy/25 fractions). Capecitabine stops on last day of RT. Interventions: Drug: Cisplatin Drug: Capecitabine Radiation: Radiotherapy Experimental: Arm 3 (carboplatin/paclitaxel+high RT dose) 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) Interventions: Drug: Carboplatin Drug: Paclitaxel Drug: Cisplatin Drug: Capecitabine Radiation: Radiotherapy Experimental: Arm 4 (Cisplatin+Capecitabine+high RT dose) 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 D1-12 Cycles 3 and 4 are given concomitantly with radiotherapy (60Gy/25 fractions). Capecitabine stops on last day of RT. Interventions: Drug: Cisplatin Drug: Capecitabine Radiation: 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 either Arm 2 or Arm 4. 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. This study will also compare the way that this treatment affects the two different cell types found in oesophageal tumours. |
| Intervention type | Other |
| Primary outcome measure | 1. Treatment failure free survival (TFFS) is measured using endoscopic biopsy and CT scan at 24 weeks 2. Overall survival is measured using clinical assessment at all trial visits up to 5 years |
| Secondary outcome measures | 1. Progression free survival is measured using CT scan and/or endoscopic biopsy for clinically suspected progression at all trial visits up to 5 years 2. Quality of life is measured using EORTC QLQ-C30 and EORTC QLQ-OES18 questionnaires at baseline, week 7, end of treatment, 6, 12 and 24 months 3. Safety is assessed by looking at toxicities using CTCAE v4.03 at baseline, after each treatment cycle, and follow up visits. Patients in the dose escalation arm will have additional assessment at 6 and 9 weeks post RT to monitor toxicities. 4. Health economics are measured by looking at health resource utilisation log and the EQ-5D at baseline, end of treatment, 6, 12 and 24 months |
| Overall study start date | 14/06/2014 |
| Completion date | 30/11/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 16 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 430; UK Sample Size: 430 |
| Total final enrolment | 439 |
| Key inclusion criteria | Current participant inclusion criteria as of 14/02/2024: Patients meeting the following criteria may be included in the trial: 1. 16 years of age or older 2. Has been selected and is fit to receive potentially curative definitive chemoradiotherapy by a specialist Upper GI MDT*. 3. Histologically confirmed adenocarcinoma, undifferentiated cancer or squamous cell carcinoma. 4. 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. 5. Tumours staged as T1-4 and N+/-, to be determined by TNM 7th (2010) edition of the AJCC/UICC manual. M1 nodes which are encompassable within the radical radiotherapy volume are eligible. 6. Total disease length (including primary tumour and involved lymph nodes) ≤13cm. The primary tumour should also be ≤10cm. 7. WHO performance status 0-1 (appendix 1). 8. 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). 9. 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). 10. Patients may receive cisplatin and capecitabine (or 5FU) OR carboplatin and paclitaxel. For those patients selected for a platinum/fluoropyrimidine but deemed unfit for cisplatin (for example but not exclusively, due to advanced age, poor renal function, neurotoxicity or clinically significant hearing impairment), they may instead receive carboplatin (AUC5) upon the discretion of the treating clinician. 11. Patients with known DPD deficiency (partial or complete) may still be eligible for SCOPE2, but sites should follow local policy with regard to appropriate fluoropyrimidine dose reduction or move to carbo-taxol regimen**. 12. Adequate haematological, hepatic and renal function, measured within 2 weeks prior to enrolment. 12.1. Absolute neutrophil count (ANC) ≥ 1.5x109/L 12.2. Platelets ≥ 100x109/L 12.3. Serum bilirubin ≤ 1.5x ULN 12.4. ALT / AST ≤ 2.5x ULN 12.5. ALP ≤ 3x ULN 12.6. Glomerular filtration rate ≥40 mls/min using locally agreed methodology. 12.6.1. If GFR ≥60 mls/min by Cockroft-Gault or equivalent (equation in section 8.1.2), dose modifications are not required. 12.6.2. If GFR is 40 to 60 ml/min and cisplatin is to be given, then formal GFR estimation (EDTA, DTPA clearance or 24-hour clearance or local institutional equivalent***) should be performed and the appropriate dose modifications for cisplatin used. Dose reduction details for GFR 40 to 60 ml/min are in section 8.6.1. Please note, if GFR is 40 to 60ml/min and carboplatin is to be given, formal GFR estimation is not mandatory. 13. Patients with reproductive potential (male or female), who are sexually active during the duration of the trial consent to using a highly effective method of contraception for at least six months after the last dose of chemoradiotherapy. Effective forms of contraception are described in section 11.6. 14. Patients who have provided written informed consent prior to enrolment. Notes * Patients not fit to receive full protocol treatment may begin treatment on 75% dose. See section 8.1.2 for further details. ** Please inform CTR if you will be giving any participants dose reduced fluoropyrimidine due to DPD deficiency. ***If using method other than EDTA, DTPA or 24 hour clearance, discuss first with CTR. Previous participant inclusion criteria: 1. Aged 17 years and over 2. Have been selected to receive potentially curative definitive chemoradiotherapy by a specialist Upper GI MDT 3. Histologically confirmed adenocarcinoma, undifferentiated cancer or squamous cell carcinoma 4. Tumours of the cervical, thoracic oesophagus, or gastrooesophageal junction (GOJ) with proximal extent of disease no more proximal than 15cm aboral and distal extent of primary tumour no more than 2 cm beyond the GOJ 5. Tumours staged with spiral CT scan, PETCT with/without endoscopic ultrasound (EUS), to be T14, N/+ (provided total tumour length including nodes is ≤10). To be eligible for PET randomisation, the PETCT must be within 4 weeks of start date of treatment 6. Total contiguous disease length ≤10cm defined by CT, EUS and/or PET. This includes ≤8cm primary tumour plus nodes within 2cm 7. WHO performance status 0 or 1 8. Adequate haematological, renal, respiratory, cardiac and hepatic function, and are fit to receive all protocol treatment 9. Patients with reproductive potential (male or female), who are sexually active during the duration of the trial, should be prepared to use a highly effective method of contraception preferably with low user dependency for at least six months after the last dose of chemoradiotherapy 10. Patients who have provided written informed consent prior to randomisation Additional inclusion criteria for patient eligibility for PET randomisation: 11. Baseline SUVmax ≥ 5 12. PET scan 14 days after start of chemo (2/+3 days from this date is acceptable) 13. Not responding to early cis/cape chemotherapy (<35% reduction in SUVmax) 14. For diabetics, fasting Blood glucose ≤12 mmol/L |
| Key exclusion criteria | Current participant exclusion criteria as of 14/02/2024: If any of the following criteria apply, patients cannot be included in the trial: 1. 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). 2. Patients with metastatic disease. (unless M1 encompassable in the radical RT field) 3. Patients with other active malignancy or past malignancy which is deemed to have significant impact on their prognosis over the next three years. 4. Patients with >2cm mucosal extension of tumour into the stomach or where the superior extent is proximal to 15 cm ab oral. 5. Patients with unstable angina or uncontrolled hypertension or cardiac failure or other clinically significant cardiac disease. 6. Patients who need continued treatment with a contraindicated concomitant medication or therapy. 7. Patients with serious infections which in the opinion of the investigator make delivery of chemotherapy inappropriate. 8. Known hypersensitivity to IMPs. 9. Women who are pregnant or breastfeeding. 10. Patients with an oesophageal stent (patients requiring a PEG/RIG/feeding jejunostomy for nutritional purposes ARE eligible). 11. Any other situation, which in the opinion of the local PI, makes the patient an unsuitable candidate for this trial. Previous participant exclusion criteria: 1. Patients who have had previous treatment for invasive oesophageal carcinoma or gastrooesophageal junction carcinoma 2. Patients with metastatic disease 3. Patients with other active malignancy or past malignancy in remission for less than 3 years except patients that have been curatively treated from the following conditions; basal cell carcinoma, Carcinomainsitu breast and carcinomainsitu cervix 4. Patients with >2cm mucosal extension of tumour into the stomach or where the superior extent is proximal to 15 cm ab oral 5. Patients with unstable angina or uncontrolled hypertension or cardiac failure or other clinically significant cardiac disease 6. Patients who need continued treatment with a contraindicated concomitant medication or therapy 7. Patients with known dihydropyrimidine dehydrogenase (DPD) deficiency 8. Patients with hearing impairment or sensorymotor neuropathy of WHO grade ≥2 9. Known hypersensitivity to IMPs 10. Women who are pregnant or breastfeeding 11. Oesophageal stent (Patients requiring a PEG/RIG/feeding jejunostomy for nutritional purposes are eligible) 12. Any other situation, which in the opinion of the local PI, makes the patient an unsuitable candidate for this trial (eg with profusely bleeding tumours where the PI has concerns about randomisation to paclitaxel/carboplatin arm where there is risk of aggravation of bleeding due to higher risk of thrombocytopenia) |
| Date of first enrolment | 14/06/2016 |
| Date of final enrolment | 16/01/2024 |
Locations
Countries of recruitment
- England
- United Kingdom
- Wales
Study participating centres
Velindre Cancer Centre
Velindre Road
Cardiff
CF14 2TL
United Kingdom
Cardiff
CF14 2TL
United Kingdom
Bristol Haematology and Oncology Centre
Horfield Road
Bristol
BS2 8ED
United Kingdom
Bristol
BS2 8ED
United Kingdom
Sponsor information
Velindre NHS Trust
Hospital/treatment centre
Hospital/treatment centre
Velindre Road
Cardiff
CF14 2TL
Wales
United Kingdom
"ROR" |
https://ror.org/05ntqkc30 |
|---|
Funders
Funder type
Charity
Cancer Research UK
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- CR_UK, Cancer Research UK - London, CRUK
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Data from all sites will be analysed together and published as soon as possible after receiving the primary end points (expected in 14/03/2024). The TMG will form the basis of the writing committee and advise on the nature of publications, subject to the Sponsor’s requirements. |
| IPD sharing plan | Trial data is the property of the trial Sponsor and will therefore will only be made available upon completion of a formal application outlining the intended use of the data. Applications will be reviewed by the TMG and TSC before data can be released. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Other publications | Embedded qualitative study | 23/09/2024 | 24/09/2024 | Yes | No |
| Other publications | Longitudinal interview study of participants' experiences of the SCOPE2 trial | 26/02/2025 | 05/03/2025 | Yes | No |
Editorial Notes
05/03/2025: Publication reference added.
24/09/2024: Publication reference added.
14/02/2024: The following changes were made:
1. IRAS number added.
2. ClinicalTrials.gov number added.
3. The overall study end date was changed from 31/12/2025 to 30/11/2026.
4. Study website added.
5. The participant inclusion criteria were changed; consequently, the age group was changed from adult to mixed and the lower age limit (number) was changed from 17 to 16.
6. The total final enrolment
7. The participant exclusion criteria were changed.
8. The recruitment end date was changed from 31/12/2023 to 16/01/2024.
11/05/2023: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/05/2023 to 31/12/2023.
2. The overall end date was changed from 14/03/2025 to 31/12/2025.
3. The intention to publish date
4. The acronym was added.
5. The total final enrolment was changed from 584 to 430.
09/08/2022: The public contact was updated.
10/01/2022: The recruitment end date has been changed from 14/12/2021 to 31/05/2023.
12/12/2019: The EudraCT number was added.
28/03/2019: The condition has been changed from "Specialty: Cancer, Primary sub-specialty: Upper GI" to "Oesophageal cancer" following a request from the NIHR.
24/11/2016: Internal review.
