Condition category
Cancer
Date applied
26/09/2016
Date assigned
20/10/2016
Last edited
16/10/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Lay summary under review with external organisation

Trial website

Contact information

Type

Scientific

Primary contact

Dr Laura Magill

ORCID ID

Contact details

Birmingham Clinical Trials Unit (BCTU)
Institute of Applied Health Research
College of Medical and Dental Sciences
Public Health Building
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
0121 415 9104
STAR-TREC@trials.bham.ac.uk

Additional identifiers

EudraCT number

2016-000862-49

ClinicalTrials.gov number

Protocol/serial number

31203

Study information

Scientific title

STAR-TREC: Saving the rectum by active surveillance or TransAnal surgery after (chemo)Radiotherapy versus Total mesorectal excision for early Rectal Cancer

Acronym

STAR-TReC

Study hypothesis

The aim of this study is to assess the feasibility of successfully recruiting to a large, multi-centre randomised trial comparing radical surgery versus organ saving treatment using (chemo)radiotherapy followed by selective transanal microsurgery, to evaluate whether it is possible to accelerate patient recruitment from 2 per month, as attained in the previous TREC study, to 6 per month over a two-year period.

Ethics approval

East Midlands – Leicester Central Research Ethics Committee, 23/09/2016, 16/EM/0186

Study design

Randomised; Interventional; Design type: Treatment, Screening, Diagnosis, Process of Care, Radiotherapy, Imaging, Complex Intervention, Management of Care, Surgery, Active Monitoring

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

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: Colorectal; UKCRC code/ Disease: Cancer/ Malignant neoplasms of digestive organs

Intervention

After all eligibility criteria have been confirmed and following informed consent, which will be conducted in accordance with Good Clinical Practice standards, and completion of the baseline assessments, patients will be randomised to one of three groups in a 1:1:1 basis using a computer-generated program at the Birmingham Clinical Trials Units (BCTU).

Group 1: Participants undergo conventional TME surgery. This will encompass both reconstructive and non-reconstructive approaches to rectal resection using the principles of TME surgery. The former includes low anterior resection, the latter abdominoperineal excision or low Hartman’s procedure. Surgeons may use either a laparoscopic, robotic or open approach to surgery. Hybrid approaches (combined laparoscopic and open) are also permitted. The quality of surgery will be measured using a standardised histopathological assessment that grades whether surgery was performed according to the principles of TME.

Group 2: Participants undergo organ using long course concurrent chemoradiation (CRT). This involves concurrent chemoradiotherapy consisting of treatment with capecitabine, administered at a dose of 825 mg/m2 bid on days of radiotherapy treatment (excluding weekend days when patients do not undergo radiotherapy treatment). Capecitabine is taken orally twice a day in equal doses for 5 days per week (normally Monday – Friday), on the days of radiotherapy administration only, throughout the 5 week course of radiotherapy. If radiotherapy is not given (e.g. due to machine maintenance or bank holiday), then capecitabine should not be given that day either. Capecitabine treatment can begin on any day of the week; however, there is normally no capecitabine treatment on Saturday or Sunday, unless radiotherapy is given on one of these days. Patients are asked to take capecitabine with a glass of water each day within 30 minutes after the ingestion of food (ideally after breakfast and evening meals), commencing the morning of the first dose of radiotherapy treatment. If patients have difficulty swallowing tablets, it is possible to dissolve the tablets in approximately 200 ml of lukewarm water. There is no stability data for any form of capecitabine suspension, so this should be done immediately prior to use and the solution swallowed immediately, rinsing to ensure all of the suspension has been ingested. As the solution has a bitter taste, flavouring with a fruit juice or squash (except grapefruit juice) is allowed.

Group 3: Participants undergo organ using short course radiotherapy (SCPRT). This involves a dose of 25Gy, applied, to the primary tumour and surrounding mesorectum in 5 fractions of 5 Gy, 5 days a week. A total dose of 25 Gy in 5 daily fractions over a total time of 1 week should be delivered, treating 5 days per week, 1 fraction per day, using 5 Gy per fraction.

For participants in group 1, surgical morbidity will be recorded post-operatively until 30 days after surgery. Follow-up after standard TME surgery will differ significantly compared to the organ preserving strategies. Both will include regular clinical follow-up as per usual national practice. Each centre can perform additional visits, endoscopies or imaging as per national protocol or patient/doctors preference. The minimal required follow-up after TME surgery will be at 30-days post-operatively and then 3, 6 12, 24 and 36 months after TME surgery and is detailed in the protocol. CT of chest-abdomen is required in order to have a reliable disease free survival of all patients in this study after 24 months. CT or MRI pelvis is also required in order to have a reliable pelvic recurrence rate of all patients in this study after 24 months. The information routinely recorded in normal clinical notes should be sufficient for completion of the annual follow-up case report forms.

For participants in groups 2 and 3, radiotherapy vwill be administered as per protocol and radiotherapy delivery and toxicities up to 3 weeks after the completion of radiotherapy will be recorded. Follow-up after (chemo)radiotherapy will include regular follow-up as per usual practice. To monitor the need for local excision, radical surgery or watchful waiting, mucosal or lymph node recurrence should be carefully monitored and additional examinations are mandatory as listed below. If patients are treated with radical surgery (TME) the follow-up schedule as described in above for patients in group 1 , ‘Clinical assessments and follow-up after TME surgery’ will be used. In the first year, all organ preserved patients will undergo a MRI and endoscopy every 3 months. CT of chest-abdomen is required in order to have a reliable disease free survival of all patients in this study after 24 months. The information routinely recorded in normal clinical notes should be sufficient for completion of the annual follow-up case report forms. If patients will undergo TME surgery because of incomplete response after (chemo)radiation therapy or in case of recurrence, follow up will be performed at 3, 4.5, 6, 9, 12, 18, 24 and 36 months after (Chemo) Radiation Therapy and specifics are detailed in the protocol.

Intervention type

Other

Phase

Drug names

Primary outcome measures

Recruitment rate is measured by recording the number of eligible participants who consent to participate in the trial at 12 and 24 months.

Secondary outcome measures

1. Ability of a single international partner to procure independent funding in year 1 is assessed through seeing whether the study being carried out internationally
2. Ability of a single international partner to open the study to recruitment in year 1 is assessed through seeing whether the study being carried out internationally
3. Organ saving rate in the experimental arms at 12 months (from randomisation) is assessed through review of data collected on the annual follow-up form
4. Proportion of patients undergoing TME surgery accurately staged and satisfying inclusion/ exclusion criteria is assessed through the MRI data collected at baseline
5. Proportion of patients identified by MRI suitable for active monitoring based on mrTRG assessment is assessed through the MRI data collected at baseline
6. Three year pelvic failure rate defined as the proportion of patients in each arm with:
6.1. Unresectable pelvic tumor
6.2. Uelvic tumour requiring beyond TME surgery
6.3. ≤1mm circumferential resection margin after TME surgery
and is assessed through the data collected on the 36 month annual follow-up for and also the 36 Month MRI scan
7. Overall survival is assessed through the annual follow-up for at 12, 24 and 36 months
8. Stoma free survival is assessed through the annual follow-up form at 30 days and 12 months post surgery
9. Health Related Quality of Life (HR QoL) measured by EORTC QLQ CR29 & C30, EuroQoL EQ-5D will be assessed baseline and 12, 24 months post randomisation
10. Bowel, bladder and sexual dysfunction measured by LARS score and ICIQ-MLUTS/ICIQ-FLUTES will be assessed baseline and 12, 24 months post randomisation

Overall trial start date

01/07/2016

Overall trial end date

01/07/2021

Reason abandoned

Eligibility

Participant inclusion criteria

1. Biopsy proven adenocarcinoma of the rectum
2. mriT1-3bN0 (with ≤5mm of mesorectal invasion) rectal tumour or endorectal ultrasound defined rectal cancer uT1- uT3b (optional: in centres where high quality ERUS is available and patient unable to tolerate MRI)
3. MDT determines that all of the following treatment options are feasible: (a) TME surgery, (b) CRT (c) SCPRT d) TEM Patients with equivocal radiological lesions e.g. mesorectal, retroperitoneal, liver, lung are eligible if agreed by MDT
4. Aged 16 or over in UK (18 or over in the Netherlands and Denmark).
5. Estimated creatinine clearance >50 mls/min
6. Absolute neutrophil count >1.5x109/l; platelets >100 x 109/L
7. Serum transaminase

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 120; UK Sample Size: 60

Participant exclusion criteria

1. Unequivocal evidence of metastatic disease (includes resectable metastases)
2. MRI node positive (defined by protocol guidelines)
3. MRI extramural vascular invasion (mriEMVI) positive (defined by protocol guidelines)
4. MRI defined mucinous tumour
5. Mesorectal fascia threatened (< 1 mm on MRI)
6. Maximum tumour diameter > 40mm as measured from everted edges on sagittal MRI
7. Tumour position anterior, above the peritoneal reflection on MRI or EUS
8. No residual luminal tumour following endoscopic resection
9. Contraindications to radiotherapy including previous pelvic radiotherapy
10. Uncontrolled cardiorespiratory comorbidity (includes patients with inadequately controlled angina or myocardial infarction within 6 months prior to randomisation)
11. Known dihydropyrimidine dehydrogenase (DPYD) deficiency
12. Known Gilberts disease (hyperbilirubinaemia)
13. Taking warfarin that cannot be discontinued at least 7 days prior to starting treatment or substituted by low molecular weight heparin
14. Taking phenytoin or sorivudine or its chemically related anologues, such as brivudine (see Section 8.4.5 for further details)
15. Pregnant, lactating or pre-menopausal women not using adequate contraception
16. Unable or unwilling to provide written informed consent

Recruitment start date

01/11/2016

Recruitment end date

31/10/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Queen Elizabeth Hospital
Mindelsohn Way Edgbaston
Birmingham
B15 2WB
United Kingdom

Trial participating centre

Bradford Royal Infirmary
Duckworth Lane
Bradford
BD9 6RJ
United Kingdom

Trial participating centre

The Christie Hospital
550 Wilmslow Road Withington
Manchester
M20 4BX
United Kingdom

Trial participating centre

Clatterbridge Centre for Oncology
Clatterbridge Road Bebington
Wirral
CH63 4JY
United Kingdom

Trial participating centre

Colchester District General Hospital
Turner Road
Colchester
C04 5JL
United Kingdom

Trial participating centre

Manchester Royal Infirmary
Oxford Road
Manchester
M13 9WL
United Kingdom

Trial participating centre

St James’s University Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom

Trial participating centre

Freeman Hospital
High Heaton
Newcastle-Upon-Tyne
NE7 7DN
United Kingdom

Trial participating centre

Birmingham Heartlands Hospital
Bordesley Green
Birmingham
B9 5ST
United Kingdom

Trial participating centre

University Hospital Aintree
Fazakerley Hospital Lowerland
Liverpool
L9 7AL
United Kingdom

Sponsor information

Organisation

University of Birmingham

Sponsor details

Research Governance Team
Birmingham
B15 2TT
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

A meeting will be held after the end of the study to allow discussion of the main results among the collaborators prior to publication. The success of STAR-TREC depends on the collaboration of a large number of clinicians across several countries. For this reason, all publications arising from this work will be attributed to the ‘STAR-TREC Collaborative Group’.
Publications will conform with the ICMJE guidelines (December 2015). When manuscripts are submitted, the corresponding author will specify the name of the STAR-TREC group, and clearly identify the group members who can take credit and responsibility for the work as authors. The byline will include the STAR-TREC name and allow MEDLINE to list the names of individual group members who are authors or who are collaborators. There will be a note associated with the byline clearly stating that the individual names are elsewhere in the paper and whether those names are authors or collaborators.
In this way, all contributors to the STAR-TREC study will be recognised.
The Trial Management Group must review any secondary publications and presentations prepared by Investigators. Authors must acknowledge that the trial was performed with the support of the funders and The University of Birmingham as study Sponsor.
Further publication details to be confirmed and will be provide in due course at a later date.

IPD Sharing plan:
The current data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

16/10/2017: Internal review. 15/09/2017: Internal review. 06/06/2017: Internal review