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

Oesophageal Cancer Clinical Trial

— SCOPE2  

Official title:

SCOPE2 - A Randomised Phase II/III Trial to Study Radiotherapy Dose Escalation in Patients With Oesophageal Cancer Treated With Definitive Chemo-radiation With an Embedded Phase II Trial for Patients With a Poor Early Response Using Positron Emission Tomography (PET)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02741856
• Other study ID #: 2014/VCC/0015
• Secondary ID: 2015-001740-11Et
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: November 4, 2016
• Est. completion date: April 2023

Study information

• Verified date: October 2018
• Source: Velindre NHS Trust
• Contact: Sarah Bridges
• Phone: +44 2920 687869
• Email: scope2[@]cardiff.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 584
• Est. completion date: April 2023
• Est. primary completion date: April 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 17 Years and older

Eligibility

Main inclusion criteria:

1. 17 years of age or older.

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 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 with endoscopic ultrasound*, CT and PET-CT to be T1-4 and N+/- (provided total tumour length including nodes is =10).

6. Total contiguous disease length =10cm defined by CT, EUS and/or PET. The primary tumour should also be =8cm.

7. WHO performance status 0 or 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 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)

11. Adequate haematological, hepatic and renal function

12. Patients agree to use effective forms of contraception during the trial (if applicable to patient).

13. Patients who have provided written informed consent prior to enrolment.

Additional inclusion criteria for patient eligibility for PET randomisation (cisplatin/capecitabine vs carboplatin/paclitaxel) as assessed at local centre:

14. Baseline SUVmax = 5.

15. PET scan 14 days after start of chemo (-2/+3 days from this date is acceptable)

16. Not responding to early cis/cape chemotherapy (this is defined as patients having a <35% reduction in SUVmax)

18. To be eligible for PET randomisation, the baseline PET-CT must have been within 4 weeks prior to start date of treatment.

Patients that are eligible for the trial but are ineligible for PET randomisation will be randomised to receive 50/60Gy radiotherapy plus cisplatin and capecitabine.

• Patients where the EUS scope is unable to pass are eligible.

Main exclusion criteria:

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 i.e. M1a or M1b according to UICC TNM version 7.

3. 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.

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.

9. Patients with serious infections

10. Known hypersensitivity to IMPs.

11. Women who are pregnant or breastfeeding.

12. Oesophageal stent (patients requiring a PEG/RIG/feeding jejunostomy for nutritional purposes are eligible).

13. Any other situation, which in the opinion of the local PI, makes the patient an unsuitable candidate for this trial.

Related Conditions & MeSH terms

• Esophageal Neoplasms
• Oesophageal Cancer

Intervention

Drug:
• Carboplatin
For more information please see the arm descriptions section.
• Paclitaxel
For more information please see the arm descriptions section.
• Cisplatin
For more information please see the arm descriptions section.
• Capecitabine
For more information please see the arm descriptions section.

Radiation:
• Radiotherapy
For more information please see the arm descriptions section.

Locations

Country	Name	City	State
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	Bristol Haematology & Oncology	Bristol
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	Kent and Canterbury	Canterbury
United Kingdom	Velindre Cancer Care Centre	Cardiff
United Kingdom	Cheltenham General Hospital	Cheltenham
United Kingdom	University Hospital Coventry	Coventry
United Kingdom	Derby Teaching Hospitals NHS Trust	Derby
United Kingdom	Glan Clwyd Hospital	Glan Clwyd
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Gloucestershire Royal Hospital	Gloucester
United Kingdom	Castle Hill Hospital	Hull
United Kingdom	The Clatterbridge Cancer Centre nhs Foundation Trust	Liverpool
United Kingdom	Guy's and St Thomas'	London
United Kingdom	Imperial College Healthcare NHS Trust	London
United Kingdom	North Middlesex Hospital	London
United Kingdom	The Royal Marsden Hospitals (Fulham)	London
United Kingdom	The James Cook University Hospital	Middlesbrough
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Peterborough and Stamford Hospitals NHS Foundation Trust	Peterborough
United Kingdom	Sheffield Teaching Hospitals - Weston Park Hospital	Sheffield
United Kingdom	University Hospital Southampton NHS Foundation Trust	Southampton
United Kingdom	The Royal Marsden Hospitals (Sutton, Surrey)	Sutton
United Kingdom	Singleton Hospital	Swansea
United Kingdom	Worcestershire Royal Hospital	Worcester
United Kingdom	Wrexham Maelor	Wrexham

Sponsors (2)

Lead Sponsor	Collaborator
Lisette Nixon	Cancer Research UK

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	Primary endpoint in squamous cell carcinoma when switching chemotherapy	24 week treatment failure free survival (TFFS).	24 weeks
Primary	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	Primary endpoint in adenocarcinoma when switching chemotherapy	24 week treatment failure free survival (TFFS).	24 weeks
Secondary	Overall survival	Overall survival assessed at each visit. Additionally patients will be flagged with the HSCIC to reduce loss to follow up.	5 years follow up
Secondary	Progression free survival	Progression free survival (PFS), additionally patients will be flagged with the HSCIC to reduce loss to follow up.	5 years
Secondary	Quality of Life	Quality of Life (QoL): EORTC QLQ-C30 and EORTC QLQ-OES18 questionnaires	Baseline, week 7, end of treatment, 6, 12 and 24 months
Secondary	Toxicity	CTCAE v4.03 at baseline, after each treatment cycle, and follow up visits. Patients in the dose escalation arm will have additional assessment and 6 and 9 weeks post RT to monitor toxicities.	After each treatment cycle and at follow up visits
Secondary	Health economics	Health economic data will be collected using health resource utilisation log plus data on health resource usage	Baseline, end of treatment, 6, 12 and 24 months