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Study of Chemoradiotherapy in Oesophageal Cancer Including PET Response and Dose Escalation (SCOPE2)

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ClinicalTrials.gov Identifier: NCT02741856
Recruitment Status : Recruiting
First Posted : April 18, 2016
Last Update Posted : October 25, 2018
Sponsor:
Collaborator:
Cancer Research UK
Information provided by (Responsible Party):
Lisette Nixon, Velindre NHS Trust

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.


Condition or disease Intervention/treatment Phase
Oesophageal Cancer Drug: Carboplatin Drug: Paclitaxel Drug: Cisplatin Drug: Capecitabine Radiation: Radiotherapy Phase 2 Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 584 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : November 4, 2016
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : April 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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)

Drug: Carboplatin
For more information please see the arm descriptions section.

Drug: Paclitaxel
For more information please see the arm descriptions section.

Drug: Cisplatin
For more information please see the arm descriptions section.

Drug: Capecitabine
For more information please see the arm descriptions section.

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

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 D1-14

Cycles 3 and 4 are given concomitantly with radiotherapy (50Gy/25 fractions). Capecitabine stops on last day of RT.

Drug: Cisplatin
For more information please see the arm descriptions section.

Drug: Capecitabine
For more information please see the arm descriptions section.

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

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)

Drug: Carboplatin
For more information please see the arm descriptions section.

Drug: Paclitaxel
For more information please see the arm descriptions section.

Drug: Cisplatin
For more information please see the arm descriptions section.

Drug: Capecitabine
For more information please see the arm descriptions section.

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

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 D1-14 Cycles 3 and 4 are given concomitantly with radiotherapy (60Gy/25 fractions). Capecitabine stops on last day of RT.

Drug: Cisplatin
For more information please see the arm descriptions section.

Drug: Capecitabine
For more information please see the arm descriptions section.

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




Primary Outcome Measures :
  1. Primary endpoint phase II in squamous cell carcinoma comparing standard dose radiotherapy to high dose radiotherapy [ Time Frame: 24 weeks ]
    24 week treatment failure free survival (TFFS).

  2. Primary endpoint phase III in squamous cell carcinoma: Overall survival (OS) comparing standard dose radiotherapy to high dose radiotherapy [ Time Frame: 24 weeks ]
    Overall survival (OS)

  3. Primary endpoint in squamous cell carcinoma when switching chemotherapy [ Time Frame: 24 weeks ]
    24 week treatment failure free survival (TFFS).

  4. Primary endpoint phase in adenocarcinoma phase II comparing standard dose radiotherapy to high dose radiotherapy [ Time Frame: 24 weeks ]
    24 week treatment failure free survival (TFFS).

  5. Primary endpoint in adenocarcinoma when switching chemotherapy [ Time Frame: 24 weeks ]
    24 week treatment failure free survival (TFFS).


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: 5 years follow up ]
    Overall survival assessed at each visit. Additionally patients will be flagged with the HSCIC to reduce loss to follow up.

  2. Progression free survival [ Time Frame: 5 years ]
    Progression free survival (PFS), additionally patients will be flagged with the HSCIC to reduce loss to follow up.

  3. Quality of Life [ Time Frame: Baseline, week 7, end of treatment, 6, 12 and 24 months ]
    Quality of Life (QoL): EORTC QLQ-C30 and EORTC QLQ-OES18 questionnaires

  4. Toxicity [ Time Frame: After each treatment cycle and at follow up visits ]
    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.

  5. Health economics [ Time Frame: Baseline, end of treatment, 6, 12 and 24 months ]
    Health economic data will be collected using health resource utilisation log plus data on health resource usage



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   17 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02741856


Contacts
Contact: Sarah Bridges +44 2920 687869 scope2@cardiff.ac.uk
Contact: Lisette Nixon, PhD +44 2920687459 nixonls@cardiff.ac.uk

Locations
United Kingdom
Aberdeen Royal Infirmary Recruiting
Aberdeen, United Kingdom
Contact: Lucy Wells         
Bristol Haematology & Oncology Recruiting
Bristol, United Kingdom
Contact: Stephen Falk         
Addenbrooke's Hospital Recruiting
Cambridge, United Kingdom
Contact: Susan Harden         
Kent and Canterbury Not yet recruiting
Canterbury, United Kingdom
Contact: Mathilda Cominos         
Velindre Cancer Care Centre Recruiting
Cardiff, United Kingdom, CF14 2TL
Contact: Carys Morgan    02920 615 888    carys.morgan6@wales.nhs.uk   
Cheltenham General Hospital Recruiting
Cheltenham, United Kingdom
Contact: Charles Candish         
University Hospital Coventry Recruiting
Coventry, United Kingdom
Contact: Sharmila Sothi         
Derby Teaching Hospitals NHS Trust Recruiting
Derby, United Kingdom
Contact: Prantik Das         
Glan Clwyd Hospital Recruiting
Glan Clwyd, United Kingdom
Contact: Angel Garcia         
Beatson West of Scotland Cancer Centre Recruiting
Glasgow, United Kingdom
Contact: David McIntosh         
Gloucestershire Royal Hospital Recruiting
Gloucester, United Kingdom
Contact: Charles Candish         
Castle Hill Hospital Recruiting
Hull, United Kingdom
Contact: Raj Roy         
The Clatterbridge Cancer Centre nhs Foundation Trust Recruiting
Liverpool, United Kingdom
Contact: Raj Sripadam         
Guy's and St Thomas' Recruiting
London, United Kingdom
Contact: Asad Qureshi         
Imperial College Healthcare NHS Trust Recruiting
London, United Kingdom
Contact: Danielle Power         
North Middlesex Hospital Recruiting
London, United Kingdom
Contact: Lucinda Melcher         
The Royal Marsden Hospitals (Fulham) Recruiting
London, United Kingdom
Contact: Katharine Aitken         
The James Cook University Hospital Recruiting
Middlesbrough, United Kingdom
Contact: David Wilson         
Churchill Hospital Recruiting
Oxford, United Kingdom
Contact: Somnath Mukherjee         
Peterborough and Stamford Hospitals NHS Foundation Trust Recruiting
Peterborough, United Kingdom
Contact: Catherine Jephcott         
Sheffield Teaching Hospitals - Weston Park Hospital Recruiting
Sheffield, United Kingdom
Contact: Jon Wadsley         
University Hospital Southampton NHS Foundation Trust Recruiting
Southampton, United Kingdom
Contact: Andrew Bateman         
The Royal Marsden Hospitals (Sutton, Surrey) Recruiting
Sutton, United Kingdom
Contact: Katharine Aitken         
Singleton Hospital Recruiting
Swansea, United Kingdom
Contact: Sarah Gwynne         
Worcestershire Royal Hospital Recruiting
Worcester, United Kingdom
Contact: Cheng Boon         
Wrexham Maelor Recruiting
Wrexham, United Kingdom
Contact: Simon Gollins         
Sponsors and Collaborators
Lisette Nixon
Cancer Research UK
Investigators
Principal Investigator: Tom Crosby Velindre University NHS Trust

Responsible Party: Lisette Nixon, Senior Trial Manager, Velindre NHS Trust
ClinicalTrials.gov Identifier: NCT02741856     History of Changes
Other Study ID Numbers: 2014/VCC/0015
2015-001740-11 ( EudraCT Number )
Ethics Reference Number ( Other Identifier: 15/WA/0395 )
First Posted: April 18, 2016    Key Record Dates
Last Update Posted: October 25, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Cisplatin
Carboplatin
Capecitabine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites