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

Phase 2
Conditions
Oesophageal Cancer
Interventions
Registration Number
NCT02741856
Lead Sponsor
Lisette Nixon
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
584
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 2 (cisplatin/capecitabine+standard RT dose)RadiotherapyCycle 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.
Arm 1 (carboplatin/paclitaxel+standard RT dose)RadiotherapyCycle 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)
Arm 4 (Cisplatin+Capecitabine+high RT dose)RadiotherapyCycle 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.
Arm 3 (carboplatin/paclitaxel+high RT dose)RadiotherapyCycle 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)
Arm 1 (carboplatin/paclitaxel+standard RT dose)CarboplatinCycle 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)
Arm 1 (carboplatin/paclitaxel+standard RT dose)PaclitaxelCycle 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)
Arm 1 (carboplatin/paclitaxel+standard RT dose)CisplatinCycle 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)
Arm 1 (carboplatin/paclitaxel+standard RT dose)CapecitabineCycle 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)
Arm 2 (cisplatin/capecitabine+standard RT dose)CisplatinCycle 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.
Arm 2 (cisplatin/capecitabine+standard RT dose)CapecitabineCycle 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.
Arm 3 (carboplatin/paclitaxel+high RT dose)CarboplatinCycle 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)
Arm 3 (carboplatin/paclitaxel+high RT dose)PaclitaxelCycle 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)
Arm 3 (carboplatin/paclitaxel+high RT dose)CisplatinCycle 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)
Arm 3 (carboplatin/paclitaxel+high RT dose)CapecitabineCycle 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)
Arm 4 (Cisplatin+Capecitabine+high RT dose)CisplatinCycle 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.
Arm 4 (Cisplatin+Capecitabine+high RT dose)CapecitabineCycle 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.
Primary Outcome Measures
NameTimeMethod
Primary endpoint phase in adenocarcinoma phase II comparing standard dose radiotherapy to high dose radiotherapy24 weeks

24 week treatment failure free survival (TFFS).

Primary endpoint phase II in squamous cell carcinoma comparing standard dose radiotherapy to high dose radiotherapy24 weeks

24 week treatment failure free survival (TFFS).

Primary endpoint in adenocarcinoma when switching chemotherapy24 weeks

24 week treatment failure free survival (TFFS).

Primary endpoint phase III in squamous cell carcinoma: Overall survival (OS) comparing standard dose radiotherapy to high dose radiotherapy24 weeks

Overall survival (OS)

Primary endpoint in squamous cell carcinoma when switching chemotherapy24 weeks

24 week treatment failure free survival (TFFS).

Secondary Outcome Measures
NameTimeMethod
Overall survival5 years follow up

Overall survival assessed at each visit. Additionally patients will be flagged with the HSCIC to reduce loss to follow up.

ToxicityAfter 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.

Progression free survival5 years

Progression free survival (PFS), additionally patients will be flagged with the HSCIC to reduce loss to follow up.

Health economicsBaseline, 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

Quality of LifeBaseline, week 7, end of treatment, 6, 12 and 24 months

Quality of Life (QoL): EORTC QLQ-C30 and EORTC QLQ-OES18 questionnaires

Trial Locations

Locations (26)

Bristol Haematology & Oncology

🇬🇧

Bristol, United Kingdom

Aberdeen Royal Infirmary

🇬🇧

Aberdeen, United Kingdom

Velindre Cancer Care Centre

🇬🇧

Cardiff, United Kingdom

Kent and Canterbury

🇬🇧

Canterbury, United Kingdom

Addenbrooke's Hospital

🇬🇧

Cambridge, 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

The Clatterbridge Cancer Centre nhs Foundation Trust

🇬🇧

Liverpool, United Kingdom

Imperial College Healthcare NHS Trust

🇬🇧

London, United Kingdom

Guy's and St Thomas'

🇬🇧

London, United Kingdom

North Middlesex Hospital

🇬🇧

London, United Kingdom

The James Cook University Hospital

🇬🇧

Middlesbrough, United Kingdom

The Royal Marsden Hospitals (Fulham)

🇬🇧

London, United Kingdom

Sheffield Teaching Hospitals - Weston Park Hospital

🇬🇧

Sheffield, United Kingdom

University Hospital Southampton NHS Foundation Trust

🇬🇧

Southampton, United Kingdom

Peterborough and Stamford Hospitals NHS Foundation Trust

🇬🇧

Peterborough, United Kingdom

Churchill Hospital

🇬🇧

Oxford, United Kingdom

The Royal Marsden Hospitals (Sutton, Surrey)

🇬🇧

Sutton, United Kingdom

Worcestershire Royal Hospital

🇬🇧

Worcester, United Kingdom

Singleton Hospital

🇬🇧

Swansea, United Kingdom

Wrexham Maelor

🇬🇧

Wrexham, United Kingdom

Castle Hill Hospital

🇬🇧

Hull, United Kingdom

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