Condition category
Cancer
Date applied
12/09/2016
Date assigned
26/10/2016
Last edited
24/11/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Public

Primary contact

Dr Ruby Ray

ORCID ID

http://orcid.org/0000-0002-8189-2930

Contact details

-
-
-
United Kingdom
+44 2920 6 87869
scope2@cardiff.ac.uk

Type

Scientific

Additional contact

Dr Chris Hurt

ORCID ID

http://orcid.org/0000-0003-1206-8355

Contact details

-
-
-
United Kingdom
+44 2920 6 87869
1@1

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

20358

Study information

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)

Acronym

Study hypothesis

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

National Institute for Social Care and Health Research Research Ethics Committee, 22/01/2016, ref: 15/WA/0392

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

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Cancer, Primary sub-specialty: Upper GI

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

Phase

Drug names

Primary outcome measures

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 trial start date

14/06/2014

Overall trial end date

14/03/2025

Reason abandoned

Eligibility

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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 584; UK Sample Size: 584

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)

Recruitment start date

14/06/2016

Recruitment end date

14/12/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Velindre Cancer Centre
Velindre Road
Cardiff
CF14 2TL
United Kingdom

Trial participating centre

Bristol Haematology and Oncology Centre
Horfield Road
Bristol
BS2 8ED
United Kingdom

Sponsor information

Organisation

Velindre NHS Trust

Sponsor details

Velindre Road
Cardiff
CF14 2TL
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Cancer Research UK

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

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.

Intention to publish date

14/03/2025

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

24/11/2016: Internal review.