Adenocarcinoma of the RectumPhase 2/3STAR-TRECNCT02945566
Can we Save the Rectum by Watchful Waiting or TransAnal Surgery Following (Chemo)Radiotherapy Versus Total Mesorectal Excision for Early REctal Cancer?
A Phase 2/3 study testing Standard TME surgery, Long course concurrent chemoradiation with capecitabine and radiotherapy and Short course radiotherapy in people with Adenocarcinoma of the Rectum, run by University of Birmingham at 5 sites in 5 countries.
Trial summary
Bowel cancer is the second most common tumour with 41 000 new cases diagnosed annually in the UK, 447 000 across Europe and 1.36 million worldwide; of which one third are located in the rectum. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Adenocarcinoma of the Rectum
- What is being tested?
- Standard TME surgery, Long course concurrent chemoradiation with capecitabine and radiotherapy and Short course radiotherapy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 380 participants
- Where
- 5 sitesin 5 countries
- Study dates
- 14 Jun 2017to Aug 2028
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Biopsy proven adenocarcinoma of the rectum
- MRI-defined ≤T3b (with ≤5mm of mesorectal invasion) rectal tumour or endorectal ultrasound-defined ≤uT3b rectal cancer (optional: in centres where high quality endorectal ultrasound (ERUS) is available or patient unable to tolerate MRI)
- MDT determines that all of the following treatment options are reasonable and feasible:
- --TME surgery, (b) CRT (c) SCRT d) TEM.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- For patients choosing organ preservation only:
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- If female and of childbearing potential, must:
- Have a negative pregnancy test within 7 days prior to study entry
- Agree to use adequate, medically approved, contraceptive precautions from trial entry until 6 months after the end of study treatment
- If non-sterilised male male with a partner of childbearing potential, must:
- Agree to use adequate, medically approved, contraceptive precautions from trial entry until 6 months after the end of study treatment
- Patient able and willing to provide written informed consent for the study
Who cannot join
- Concomitant or previous malignancies within 3 years prior to trial entry, except those that in the opinion of the MDT are unlikely to relapse within 3 years or lead to death within 5 years
- Unequivocal evidence of metastatic disease (includes resectable metastases)
- -- Patients with equivocal radiological lesions (e.g. retroperitoneal, liver, lung) that are not classified as M1 are eligible if agreed by MDT
- MRI node positive (≥N1, defined by protocol guidelines)
- -- Patients with equivocal radiological findings that are either classified as NX or N0 are eligible
- MRI extramural vascular invasion (mriEMVI) positive (defined by protocol guidelines)
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- MRI defined mucinous tumour
- Mesorectal fascia threatened (≤1 mm on MRI or ERUS)
- Maximum tumour diameter > 40mm (either measured from everted edges on sagittal MRI or on ERUS)
- Tumour position anterior, above the peritoneal reflection on MRI or EUS
- No residual luminal tumour following endoscopic resection
- Contraindications to radiotherapy including previous pelvic radiotherapy
- Uncontrolled cardiorespiratory comorbidity (includes patients with inadequately controlled angina or myocardial infarction or arrhythmia within 6 months prior to trial entry)
- Known complete dihydropyrimidine dehydrogenase (DPYD) deficiency
- Known Gilbert's disease (hyperbilirubinaemia)
- Taking coumarin-derivative anticoagulants (e.g. warfarin) that cannot be discontinued at least 7 days prior to starting treatment or substituted by low molecular weight heparin
- Taking phenytoin or sorivudine or its chemically related anologues, such as brivudine, within 4 weeks of trial entry (see Section 8.3.5 for further details)
- Taking metronidazole at study entry
- Pregnant or lactating women
- History of severe and unexpected reactions to fluoropyrimidine therapy
- Age <16 years (UK), <18 years (other countries)
Trial locations and contacts
5 sites in 5 countries.
5 sites in 5 countries
About this study
Official title: STAR-TREC: Can we Save the Rectum by Watchful Waiting or TransAnal Surgery Following (Chemo)Radiotherapy Versus Total Mesorectal Excision for Early REctal Cancer?
Bowel cancer is the second most common tumour with 41 000 new cases diagnosed annually in the UK, 447 000 across Europe and 1.36 million worldwide; of which one third are located in the rectum. Standard primary radical Total Mesorectal Excision (TME) surgery is an oncologically effective treatment for early stage rectal cancer. However, resection of a low rectal tumour requires a permanent stoma in approximately 10% of cases while many more patients have a temporary stoma, some of which are not reversed. Radical surgery, which evolved to treat locally advanced, symptomatic tumours, may not be the optimal method of treatment for early screen-detected tumours and an organ preserving strategy may generate significantly less morbidity without substantially compromising oncological outcomes.
STAR-TREC is a rolling phase II/III study. Phase II aimed to assess the feasibility of a large, multi-centre randomised trial comparing radical surgery versus two contrasting organ saving treatments followed by selective transanal microsurgery. Phase III will evaluate two contrasting organ preservation strategies in terms of organ preservation rates, toxicity (clinician and patient-reported) and Health-Related Quality of Life (HRQoL).
Read the detailed description
The Phase II component of STAR-TREC (now completed) was a randomised, three arm (1:1:1) study using the following arms:
- Standard TME surgery (control)
- Organ saving treatments using:
- Long course concurrent chemoradiation:
- Capecitabine: 825 mg/m² orally, b.d., on radiotherapy days
- Radiotherapy: A dose of 50 Gy applied to the primary tumour and surrounding mesorectum in 25 fractions of 2 Gy, 5 days a week.
- Short course radiotherapy:
- A dose of 25 Gy applied to the primary tumour and surrounding mesorectum in 5 fractions of 5 Gy, 5 days a week.
The phase III component of STAR_TREC is now open and has a partially randomised patient preference design where patients choose between organ saving treatment or standard surgery.
Those who prefer organ preservation will undergo randomisation 1:1 between:
- Long course concurrent chemoradiation (as described above)
- Short course radiotherapy (as described above)
Those who prefer standard surgery or have no preference, will undergo standard TME surgery without neoadjuvant radiotherapy treatment.
For organ-preserving strategies in phase II and III, clinical response to radiotherapy determines the next treatment step. Radiotherapy response is evaluated using clinical exam, endoscopy and MRI. The first assessment at 11-13 weeks (from radiotherapy start) using composite clinical, endoscopic and MRI based assessment will identify a minority of non-responders who should convert to TME surgery. Patients demonstrating a satisfactory radiotherapy response at 11-13 weeks will be reassessed by endoscopy at 16-20 weeks. Re-evaluation at 16-20 weeks determines if the STAR-TREC criteria for complete response (CR) are met. Patients who achieve CR may progress directly to active surveillance. Those who do not fulfil the criteria for CR will progress to excision biopsy with transanal endoscopic microsurgery (TEM).
The phase II component of the study aimed to evaluate the feasibility of accelerating patient recruitment from 2 per month, as attained in the previous TREC study, to 6 per month internationally over a two-year period.
The STAR-TREC phase III study will evaluate whether a CRT or SCRT organ preservation strategy leads to higher organ preservation rates and should become first line treatment for early rectal cancer.
This objective can be divided into two main questions:
- Determine the optimal radiation schedule to achieve the highest rate of organ preservation
- Determine the optimal radiation schedule to achieve the best quality of life after organ preservation
- Conditions
- Adenocarcinoma of the Rectum
- Being tested
- Standard TME surgery, Long course concurrent chemoradiation with capecitabine and radiotherapy, Short course radiotherapy
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard TME surgeryProcedure or surgery
Total mesorectal excision
Long course concurrent chemoradiation with capecitabine and radiotherapyDrug
Also called Xeloda is the brand name for capecitabine
Capecitabine 825 mg/m² orally, b.i.d., on radiotherapy days. Radiotherapy: A dose of 50 Gy, applied to the primary tumour and surrounding mesorectum, in 25 fractions of 2 Gy, 5 days a week.
Short course radiotherapyRadiation
A dose of 25Gy, applied, to the primary tumour and surrounding mesorectum in 5 fractions of 5 Gy, 5 days a week.
| Study group | Role | What they receive |
|---|---|---|
| Standard TME surgery | Active comparator | Radical total mesorectal excision Receives: Procedure: Standard TME surgery |
| Long course concurrent chemoradiation | Experimental | Capecitabine: 825 mg/m² orally, b.i.d., on radiotherapy days Radiotherapy: A dose of 50 Gy, applied to the primary tumour and surrounding mesorectum, in 25 fractions of 2 Gy, 5 days a week. Receives: Drug: Long course concurrent chemoradiation with capecitabine and radiotherapy |
| Short course radiotherapy | Experimental | A dose of 25Gy, applied, to the primary tumour and surrounding mesorectum in 5 fractions of 5 Gy, 5 days a week. Receives: Radiation: Short course radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase II (Feasibility study) Primary Outcome: Recruitment Rate
Measured at 12 and 24 months. Target recruitment rates are ≥4 and ≥6 patients randomised per month at 12 and 24 months respectively for total accrual of 120 international cases. Each individual country will attempt to exceed the minimum recruitment required to sustain phase III (UK 75, the Netherlands 75, Denmark 30). If recruitment is on target in year two then consideration will be given to an early application for transition to phase III with a funding application and a formal protocol amendment.
Measured: 24 Months
Phase III Primary Outcome: Organ Preservation
The primary endpoint of the STAR-TREC phase III study is the proportion of patients with successful organ preservation at 30 months from the start day of (chemo)radiotherapy treatment. This endpoint will be assessed for patients who prefer organ preservation and is defined as an in-situ rectum (includes patients subject to transanal local resection), no defunctioning stoma and an absence of active loco-regional cancer failure. The expected incidence of this outcome is approximately 60%.
Measured: 30 Months from start day of (chemo)radiotherapy treatment.
Secondary outcomes (38)
Phase II (Feasibility study): Core Endpoint - Funding
Incidence of procurement of funding by one STAR-TREC international partner
Measured: 12 Months
Phase II (Feasibility study): Core Endpoint - International Recruitment
Incidence of opening of STAR-TREC by one international partner
Measured: 12 Months
Phase II (Feasibility study): Core Endpoint - Efficacy
Efficacy of organ preserving treatment arm on completion of phase II study: Is the organ saving rate more than 50% of patients with early stage rectal cancer at 12 months (following randomisation) achieved in the experimental arms? [Name of Measurement: Rate of organ saving >50% at 12 months; Unit of Measurement: no record of radical surgery at 12 months]
Measured: 12 Months
Phase II: Safety- Accuracy of MRI in predicting STAR-TREC eligibility
MRI
- Accuracy of MRI in predicting STAR-TREC eligibility (We will report the accuracy of MRI based patient selection according to each national standard, compared to the reference standard of post-operative histological staging. STAR-TREC will help develop international consensus in MRI reporting of mesorectal lymph node involvement by rectal cancer)
Measured: 24 Months
Phase II: Safety - 30 day Mortality
- Mortality
Measured: 30 days
Phase II: Safety - 6 month Mortality
- Mortality
Measured: 6 Months
Phase II: Safety - Surgical Morbidity
- Surgical morbidity
Measured: 36 Months
Phase II: Safety - Tumour Recurrence/ Regrowth within Bowel Wall
- Rate of tumour recurrence or regrowth within the bowel wall (experimental arm)
Measured: 36 Months
Phase II: Safety - Tumour Recurrence within Mesorectum
- Rate of tumour recurrence within the mesorectum (experimental arm)
Measured: 36 Months
Phase II: Safety - Distant Metastasis
- Rate of distant metastases
Measured: 36 Months
Phase II: Safety - Pelvic Failure
- Pelvic failure rate: expressed as a sum of the following (i) unresectable pelvic tumour, (ii) cases requiring beyond TME surgery or (iii) tumour recurrence or regrowth ≤1mm from the circumferential surgical margin after TME surgery.
Measured: 36 Months
Phase II: Safety - Bowel
Bowel dysfunction measured by EORTC QLQ CR29 [The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) ColoRectal cancer (CR) with 29 items] \& C30 [The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core with 30 items], LARS score [The Low Anterior Resection Syndrome score], and ICIQ-MLUTS/ICIQ-FLUTS [International Consultation on Incontinence Questionnaire Male/Female Lower Urinary Tract Symptoms Module]. Multiple measurements and scores will be aggregated to arrive at one reported value. Scores at different time points after randomisation will be compared to baseline scores.
Measured: 36 Months
Phase II: Safety - Bladder
Bladder dysfunction measured by EORTC QLQ CR29 [The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) ColoRectal cancer (CR) with 29 items] \& C30 [The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core with 30 items], LARS score [The Low Anterior Resection Syndrome score], and ICIQ-MLUTS/ICIQ-FLUTS [International Consultation on Incontinence Questionnaire Male/Female Lower Urinary Tract Symptoms Module]. Multiple measurements and scores will be aggregated to arrive at one reported value. Scores at different time points after randomisation will be compared to baseline scores.
Measured: 36 Months
Phase II: Safety - Sexual dysfunction
Sexual dysfunction measured by EORTC QLQ CR29 [The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) ColoRectal cancer (CR) with 29 items] \& C30 [The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core with 30 items], LARS score [The Low Anterior Resection Syndrome score], and ICIQ-MLUTS/ICIQ-FLUTS [International Consultation on Incontinence Questionnaire Male/Female Lower Urinary Tract Symptoms Module]. Multiple measurements and scores will be aggregated to arrive at one reported value. Scores at different time points after randomisation will be compared to baseline scores.
Measured: 36 Months
Phase II: Efficacy - Stoma
Additional outcome measures pertinent to the phase III study examining the efficacy of organ saving versus standard surgery will also be collected:
- Proportion of patients with/ without a stoma at 30 days and one year
Measured: 24 Months
Phase II: Efficacy - Tumour Down-staging
- Histopathological assessment of tumour down-staging following radiotherapy according to depth of tumour invasion and the incidence of other high-risk features in comparison to non-irradiated (control) group
Measured: 4.5 Months
Phase II: Efficacy - Active Monitoring
- Proportion of patients identified by clinical and MRI assessment as suitable for active monitoring
Measured: 4.5 Months
Phase II: Efficacy - Conversion Rate
- Conversion rates from organ saving to radical surgery
Measured: 36 Months
Phase II: Efficacy - Disease Survival
- Disease free survival
Measured: 36 Months
Phase II: Efficacy - Health-related Quality of Life score
Quality of life measured by EORTC QLQ CR29 [The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) ColoRectal cancer (CR) with 29 items] \& C30 [The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core with 30 items], LARS score [The Low Anterior Resection Syndrome score], and ICIQ-MLUTS/ICIQ-FLUTS [International Consultation on Incontinence Questionnaire Male/Female Lower Urinary Tract Symptoms Module]. Multiple measurements and scores will be aggregated to arrive at one reported value. Scores at different time points after randomisation will be compared to baseline scores.
Measured: 3 months
Phase II: Efficacy - Health-related Quality of Life score
Quality of life measured by EORTC QLQ CR29 [The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) ColoRectal cancer (CR) with 29 items] \& C30 [The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core with 30 items], LARS score [The Low Anterior Resection Syndrome score], and ICIQ-MLUTS/ICIQ-FLUTS [International Consultation on Incontinence Questionnaire Male/Female Lower Urinary Tract Symptoms Module]. Multiple measurements and scores will be aggregated to arrive at one reported value. Scores at different time points after randomisation will be compared to baseline scores.
Measured: 12 Months
Phase II: Efficacy - Health-related Quality of Life score
Quality of life measured by EORTC QLQ CR29 [The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) ColoRectal cancer (CR) with 29 items] \& C30 [The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core with 30 items], LARS score [The Low Anterior Resection Syndrome score], and ICIQ-MLUTS/ICIQ-FLUTS [International Consultation on Incontinence Questionnaire Male/Female Lower Urinary Tract Symptoms Module]. Multiple measurements and scores will be aggregated to arrive at one reported value. Scores at different time points after randomisation will be compared to baseline scores.
Measured: 24 Months
Phase II: Efficacy - Health-related Quality of Life score
Quality of life measured by EORTC QLQ CR29 [The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) ColoRectal cancer (CR) with 29 items] \& C30 [The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core with 30 items], LARS score [The Low Anterior Resection Syndrome score], and ICIQ-MLUTS/ICIQ-FLUTS [International Consultation on Incontinence Questionnaire Male/Female Lower Urinary Tract Symptoms Module]. Multiple measurements and scores will be aggregated to arrive at one reported value. Scores at different time points after randomisation will be compared to baseline scores.
Measured: 36 Months
Phase II: Efficacy - Overall Survival
- Overall survival
Measured: 36 Months
Phase III: For the randomised comparison between organ-preserving strategies
Clinician-reported acute treatment related toxicity up to 30 days following completion of (chemo)radiotherapy
Measured: 30 days from start day of (chemo)radiotherapy treatment.
Phase III: Complete Response *For the randomised comparison between organ-preserving strategies
Proportion of patients with Complete Response to (chemo)radiation therapy
Measured: 30 months
Phase III: For the randomised comparison between organ-preserving strategies - Local Excision
Proportion of patients undergoing transanal local excision
Measured: 20 weeks
Phase III: For the randomised comparison between organ-preserving strategies - Organ Loss
Time to event of organ loss assessed for patients who prefer organ preservation
Measured: Defined as the length of time from the start date of trial treatment until TME surgery
Phase III: For the randomised comparison between organ-preserving strategies - Non-Regrowth
Non-regrowth pelvic tumour control to 36 months; defined as the length of time from the start date of trial treatment until death (any cause) or development of unequivocal pelvic recurrence but not including patients who developed local regrowth which was resected with clear margins using standard TME surgery
Measured: 36 months
Phase III: For the randomised comparison between organ-preserving strategies - Metastasis Free Survival
Metastasis free survival to 36 months; defined as the length of time from the start date of trial treatment until death (any cause) or detection of distant metastasis
Measured: 36 months
Phase III: For the randomised comparison between organ-preserving strategies - Non-regrowth Disease Free Survival
Non-regrowth -disease free survival to 36 months; defined as the length of time from the start of trial treatment until death (any cause), detection of local pelvic recurrence or distant metastasis but not including patients who developed local regrowth which was resected with clear margins using standard TME surgery
Measured: 36 months
Phase III: For the randomised comparison between organ-preserving strategies - Overall Survival
Overall survival to 60 months defined as the length of time from the start date of trial treatment until death (any cause)
Measured: 60 months
Phase III: For analyses incorporating the non-randomised standard surgery comparator - Toxicity
Clinician-reported acute treatment related toxicity up to 30 days following completion of (chemo)radiotherapy or date of initial surgery
Measured: 30 days
Phase III: For analyses incorporating the non-randomised standard surgery comparator - Non-regrowth Pelvic Tumour Control
Non-regrowth pelvic tumour control to 36 months; defined as the length of time from the start date of (chemo)radiotherapy or date of initial surgery until death (any cause) or development of unequivocal pelvic recurrence but not including patients who preferred organ preservation and developed local regrowth which was resected with clear margins using standard TME surgery
Measured: 36 months
Phase III: For analyses incorporating the non-randomised standard surgery comparator - Metastasis Free Survival
Metastasis-free survival to 36 months; defined as the length of time from the start date of trial treatment or date of initial surgery until death (any cause) or detection of distant metastasis
Measured: 36 months
Phase III: For analyses incorporating the non-randomised standard surgery comparator - Disease-free Survival
Disease-free survival to 36 months; defined as the length of time from the start date of trial treatment or date of initial surgery until death (any cause), detection of local pelvic recurrence or distant metastasis but not including patients who developed local regrowth which was resected with clear margins using standard TME surgery
Measured: 36 months
Phase III: For analyses incorporating the non-randomised standard surgery comparator - Overall Survival
Overall survival to 60 months defined as the length of time from the start date of trial treatment or date of initial surgery until death (any cause))
Measured: 60 months
Phase III: For analyses incorporating the non-randomised standard surgery comparator - Decision Regret
Decision regret at 24 months measured using the validated Decision regret scale questionnaire. The Decision Regret Scale is a 5-item Likert-type measure written to assess regret or remorse following a medical decision that takes less than 5 minutes to complete. High scores suggest high regret over a health care decision. Scores may be transformed to a scale of 0 (no regret) to 100 (high regret).
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2016 (estimated)
- Study start14 Jun 2017
- Primary completionAug 2027 (estimated)
- Study completionAug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Adenocarcinoma of the RectumStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 380 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Simon Bach, MD, Principal investigator, University Hospitals Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02945566
- Sponsor's protocol ID
- RG_15-011
- Other IDs
- 2016-000862-49, 2016
- Acronym
- STAR-TREC
- Status last verified
- Jun 2026
- First submitted
- 25 Jul 2016
- Last updated
- 29 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Motamedi MAK, Mak NT, Brown CJ, Raval MJ, Karimuddin AA, Giustini D, Phang PT. Local versus radical surgery for early rectal cancer with or without neoadjuvant or adjuvant therapy. Cochrane Database Syst Rev. 2023 Jun 13;6(6):CD002198. doi: 10.1002/14651858.CD002198.pub3.
PubMed 37310167Appelt AL, Kerkhof EM, Nyvang L, Harderwijk EC, Abbott NL, Teo M, Peters FP, Kronborg CJS, Spindler KG, Sebag-Montefiore D, Marijnen CAM; STAR-TREC collaborative group. Robust dose planning objectives for mesorectal radiotherapy of early stage rectal cancer - A multicentre dose planning study. Tech Innov Patient Support Radiat Oncol. 2019 Oct 15;11:14-21. doi: 10.1016/j.tipsro.2019.09.001. eCollection 2019 Sep.
PubMed 32095545van den Ende RPJ, Peters FP, Harderwijk E, Rutten H, Bouwmans L, Berbee M, Canters RAM, Stoian G, Compagner K, Rozema T, de Smet M, Intven MPW, Tijssen RHN, Theuws J, van Haaren P, van Triest B, Eekhout D, Marijnen CAM, van der Heide UA, Kerkhof EM. Radiotherapy quality assurance for mesorectum treatment planning within the multi-center phase II STAR-TReC trial: Dutch results. Radiat Oncol. 2020 Feb 18;15(1):41. doi: 10.1186/s13014-020-01487-6.
PubMed 32070386Rombouts AJM, Al-Najami I, Abbott NL, Appelt A, Baatrup G, Bach S, Bhangu A, Garm Spindler KL, Gray R, Handley K, Kaur M, Kerkhof E, Kronborg CJ, Magill L, Marijnen CAM, Nagtegaal ID, Nyvang L, Peters FP, Pfeiffer P, Punt C, Quirke P, Sebag-Montefiore D, Teo M, West N, de Wilt JHW; for STAR-TREC Collaborative Group. Can we Save the rectum by watchful waiting or TransAnal microsurgery following (chemo) Radiotherapy versus Total mesorectal excision for early REctal Cancer (STAR-TREC study)?: protocol for a multicentre, randomised feasibility study. BMJ Open. 2017 Dec 28;7(12):e019474. doi: 10.1136/bmjopen-2017-019474.
PubMed 29288190
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- STAR-TREC: Can we Save the Rectum by Watchful Waiting or TransAnal Surgery Following (Chemo)Radiotherapy Versus Total Mesorectal Excision for Early REctal Cancer?
- ClinicalTrials.gov ID
- NCT02945566
- Acronym / sponsor ID
- STAR-TREC / RG_15-011
- Conditions
- Adenocarcinoma of the Rectum
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 380 participants (estimated)
- Lead sponsor
- University of BirminghamUniversity, hospital or other
- Study start
- 14 Jun 2017 (actual)
- Primary completion
- Aug 2027 (estimated)
- Study completion
- Aug 2028 (estimated)
- First posted
- 26 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Bowel cancer is the second most common tumour with 41 000 new cases diagnosed annually in the UK, 447 000 across Europe and 1.36 million worldwide; of which one third are located in the rectum. Standard primary radical Total Mesorectal Excision (TME) surgery is an oncologically effective treatment for early stage rectal cancer. However, resection of a low rectal tumour requires a permanent stoma in approximately 10% of cases while many more patients have a temporary stoma, some of which are not reversed. Radical surgery, which evolved to treat locally advanced, symptomatic tumours, may not be the optimal method of treatment for early screen-detected tumours and an organ preserving strategy may generate significantly less morbidity without substantially compromising oncological outcomes.
STAR-TREC is a rolling phase II/III study. Phase II aimed to assess the feasibility of a large, multi-centre randomised trial comparing radical surgery versus two contrasting organ saving treatments followed by selective transanal microsurgery. Phase III will evaluate two contrasting organ preservation strategies in terms of organ preservation rates, toxicity (clinician and patient-reported) and Health-Related Quality of Life (HRQoL).
Detailed description
The Phase II component of STAR-TREC (now completed) was a randomised, three arm (1:1:1) study using the following arms:
- Standard TME surgery (control)
- Organ saving treatments using:
- Long course concurrent chemoradiation:
- Capecitabine: 825 mg/m² orally, b.d., on radiotherapy days
- Radiotherapy: A dose of 50 Gy applied to the primary tumour and surrounding mesorectum in 25 fractions of 2 Gy, 5 days a week.
- Short course radiotherapy:
- A dose of 25 Gy applied to the primary tumour and surrounding mesorectum in 5 fractions of 5 Gy, 5 days a week.
The phase III component of STAR_TREC is now open and has a partially randomised patient preference design where patients choose between organ saving treatment or standard surgery.
Those who prefer organ preservation will undergo randomisation 1:1 between:
- Long course concurrent chemoradiation (as described above)
- Short course radiotherapy (as described above)
Those who prefer standard surgery or have no preference, will undergo standard TME surgery without neoadjuvant radiotherapy treatment.
For organ-preserving strategies in phase II and III, clinical response to radiotherapy determines the next treatment step. Radiotherapy response is evaluated using clinical exam, endoscopy and MRI. The first assessment at 11-13 weeks (from radiotherapy start) using composite clinical, endoscopic and MRI based assessment will identify a minority of non-responders who should convert to TME surgery. Patients demonstrating a satisfactory radiotherapy response at 11-13 weeks will be reassessed by endoscopy at 16-20 weeks. Re-evaluation at 16-20 weeks determines if the STAR-TREC criteria for complete response (CR) are met. Patients who achieve CR may progress directly to active surveillance. Those who do not fulfil the criteria for CR will progress to excision biopsy with transanal endoscopic microsurgery (TEM).
The phase II component of the study aimed to evaluate the feasibility of accelerating patient recruitment from 2 per month, as attained in the previous TREC study, to 6 per month internationally over a two-year period.
The STAR-TREC phase III study will evaluate whether a CRT or SCRT organ preservation strategy leads to higher organ preservation rates and should become first line treatment for early rectal cancer.
This objective can be divided into two main questions:
- Determine the optimal radiation schedule to achieve the highest rate of organ preservation
- Determine the optimal radiation schedule to achieve the best quality of life after organ preservation
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Standard TME surgery | Active comparator | Procedure: Standard TME surgeryRadical total mesorectal excision |
| Long course concurrent chemoradiation | Experimental | Drug: Long course concurrent chemoradiation with capecitabine and radiotherapyCapecitabine: 825 mg/m² orally, b.i.d., on radiotherapy days Radiotherapy: A dose of 50 Gy, applied to the primary tumour and surrounding mesorectum, in 25 fractions of 2 Gy, 5 days a week. |
| Short course radiotherapy | Experimental | Radiation: Short course radiotherapyA dose of 25Gy, applied, to the primary tumour and surrounding mesorectum in 5 fractions of 5 Gy, 5 days a week. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- Biopsy proven adenocarcinoma of the rectum
- MRI-defined ≤T3b (with ≤5mm of mesorectal invasion) rectal tumour or endorectal ultrasound-defined ≤uT3b rectal cancer (optional: in centres where high quality endorectal ultrasound (ERUS) is available or patient unable to tolerate MRI)
- MDT determines that all of the following treatment options are reasonable and feasible:
- --TME surgery, (b) CRT (c) SCRT d) TEM.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Key exclusion criteria (21 listed)
- Concomitant or previous malignancies within 3 years prior to trial entry, except those that in the opinion of the MDT are unlikely to relapse within 3 years or lead to death within 5 years
- Unequivocal evidence of metastatic disease (includes resectable metastases)
- -- Patients with equivocal radiological lesions (e.g. retroperitoneal, liver, lung) that are not classified as M1 are eligible if agreed by MDT
- MRI node positive (≥N1, defined by protocol guidelines)
- -- Patients with equivocal radiological findings that are either classified as NX or N0 are eligible
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard TME surgeryTotal mesorectal excision | Procedure or surgery | Standard TME surgery |
| Long course concurrent chemoradiation with capecitabine and radiotherapyAlso: Xeloda is the brand name for capecitabineCapecitabine 825 mg/m² orally, b.i.d., on radiotherapy days. Radiotherapy: A dose of 50 Gy, applied to the primary tumour and surrounding mesorectum, in 25 fractions of 2 Gy, 5 days a week. | Drug | Long course concurrent chemoradiation |
| Short course radiotherapyA dose of 25Gy, applied, to the primary tumour and surrounding mesorectum in 5 fractions of 5 Gy, 5 days a week. | Radiation | Short course radiotherapy |
Primary outcome
Phase II (Feasibility study) Primary Outcome: Recruitment Rate
Time frame: 24 Months
Measured at 12 and 24 months. Target recruitment rates are ≥4 and ≥6 patients randomised per month at 12 and 24 months respectively for total accrual of 120 international cases. Each individual country will attempt to exceed the minimum recruitment required to sustain phase III (UK 75, the Netherlands 75, Denmark 30). If recruitment is on target in year two then consideration will be given to an early application for transition to phase III with a funding application and a formal protocol amendment.
Phase III Primary Outcome: Organ Preservation
Time frame: 30 Months from start day of (chemo)radiotherapy treatment.
The primary endpoint of the STAR-TREC phase III study is the proportion of patients with successful organ preservation at 30 months from the start day of (chemo)radiotherapy treatment. This endpoint will be assessed for patients who prefer organ preservation and is defined as an in-situ rectum (includes patients subject to transanal local resection), no defunctioning stoma and an absence of active loco-regional cancer failure. The expected incidence of this outcome is approximately 60%.
38 secondary outcomes
Phase II (Feasibility study): Core Endpoint - Funding
Time frame: 12 Months
Phase II (Feasibility study): Core Endpoint - International Recruitment
Time frame: 12 Months
Phase II (Feasibility study): Core Endpoint - Efficacy
Time frame: 12 Months
Phase II: Safety- Accuracy of MRI in predicting STAR-TREC eligibility
Time frame: 24 Months
Phase II: Safety - 30 day Mortality
Time frame: 30 days
Phase II: Safety - 6 month Mortality
Time frame: 6 Months
Phase II: Safety - Surgical Morbidity
Time frame: 36 Months
Phase II: Safety - Tumour Recurrence/ Regrowth within Bowel Wall
Time frame: 36 Months
Phase II: Safety - Tumour Recurrence within Mesorectum
Time frame: 36 Months
Phase II: Safety - Distant Metastasis
Time frame: 36 Months
Phase II: Safety - Pelvic Failure
Time frame: 36 Months
Phase II: Safety - Bowel
Time frame: 36 Months
Phase II: Safety - Bladder
Time frame: 36 Months
Phase II: Safety - Sexual dysfunction
Time frame: 36 Months
Phase II: Efficacy - Stoma
Time frame: 24 Months
Phase II: Efficacy - Tumour Down-staging
Time frame: 4.5 Months
Phase II: Efficacy - Active Monitoring
Time frame: 4.5 Months
Phase II: Efficacy - Conversion Rate
Time frame: 36 Months
Phase II: Efficacy - Disease Survival
Time frame: 36 Months
Phase II: Efficacy - Health-related Quality of Life score
Time frame: 3 months
Phase II: Efficacy - Health-related Quality of Life score
Time frame: 12 Months
Phase II: Efficacy - Health-related Quality of Life score
Time frame: 24 Months
Phase II: Efficacy - Health-related Quality of Life score
Time frame: 36 Months
Phase II: Efficacy - Overall Survival
Time frame: 36 Months
Phase III: For the randomised comparison between organ-preserving strategies
Time frame: 30 days from start day of (chemo)radiotherapy treatment.
Phase III: Complete Response *For the randomised comparison between organ-preserving strategies
Time frame: 30 months
Phase III: For the randomised comparison between organ-preserving strategies - Local Excision
Time frame: 20 weeks
Phase III: For the randomised comparison between organ-preserving strategies - Organ Loss
Time frame: Defined as the length of time from the start date of trial treatment until TME surgery
Phase III: For the randomised comparison between organ-preserving strategies - Non-Regrowth
Time frame: 36 months
Phase III: For the randomised comparison between organ-preserving strategies - Metastasis Free Survival
Time frame: 36 months
Phase III: For the randomised comparison between organ-preserving strategies - Non-regrowth Disease Free Survival
Time frame: 36 months
Phase III: For the randomised comparison between organ-preserving strategies - Overall Survival
Time frame: 60 months
Phase III: For analyses incorporating the non-randomised standard surgery comparator - Toxicity
Time frame: 30 days
Phase III: For analyses incorporating the non-randomised standard surgery comparator - Non-regrowth Pelvic Tumour Control
Time frame: 36 months
Phase III: For analyses incorporating the non-randomised standard surgery comparator - Metastasis Free Survival
Time frame: 36 months
Phase III: For analyses incorporating the non-randomised standard surgery comparator - Disease-free Survival
Time frame: 36 months
Phase III: For analyses incorporating the non-randomised standard surgery comparator - Overall Survival
Time frame: 60 months
Phase III: For analyses incorporating the non-randomised standard surgery comparator - Decision Regret
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2026.
- Derived from this study: PubMed 37310167Motamedi MAK, Mak NT, Brown CJ, Raval MJ, Karimuddin AA, Giustini D, Phang PT. Local versus radical surgery for early rectal cancer with or without neoadjuvant or adjuvant therapy. Cochrane Database Syst Rev. 2023 Jun 13;6(6):CD002198. doi: 10.1002/14651858.CD002198.pub3.
- Derived from this study: PubMed 32095545Appelt AL, Kerkhof EM, Nyvang L, Harderwijk EC, Abbott NL, Teo M, Peters FP, Kronborg CJS, Spindler KG, Sebag-Montefiore D, Marijnen CAM; STAR-TREC collaborative group. Robust dose planning objectives for mesorectal radiotherapy of early stage rectal cancer - A multicentre dose planning study. Tech Innov Patient Support Radiat Oncol. 2019 Oct 15;11:14-21. doi: 10.1016/j.tipsro.2019.09.001. eCollection 2019 Sep.
- Derived from this study: PubMed 32070386van den Ende RPJ, Peters FP, Harderwijk E, Rutten H, Bouwmans L, Berbee M, Canters RAM, Stoian G, Compagner K, Rozema T, de Smet M, Intven MPW, Tijssen RHN, Theuws J, van Haaren P, van Triest B, Eekhout D, Marijnen CAM, van der Heide UA, Kerkhof EM. Radiotherapy quality assurance for mesorectum treatment planning within the multi-center phase II STAR-TReC trial: Dutch results. Radiat Oncol. 2020 Feb 18;15(1):41. doi: 10.1186/s13014-020-01487-6.
- Derived from this study: PubMed 29288190Rombouts AJM, Al-Najami I, Abbott NL, Appelt A, Baatrup G, Bach S, Bhangu A, Garm Spindler KL, Gray R, Handley K, Kaur M, Kerkhof E, Kronborg CJ, Magill L, Marijnen CAM, Nagtegaal ID, Nyvang L, Peters FP, Pfeiffer P, Punt C, Quirke P, Sebag-Montefiore D, Teo M, West N, de Wilt JHW; for STAR-TREC Collaborative Group. Can we Save the rectum by watchful waiting or TransAnal microsurgery following (chemo) Radiotherapy versus Total mesorectal excision for early REctal Cancer (STAR-TREC study)?: protocol for a multicentre, randomised feasibility study. BMJ Open. 2017 Dec 28;7(12):e019474. doi: 10.1136/bmjopen-2017-019474.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Simon Bach, MD principal investigator
University Hospitals Birmingham
5 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Standard TME surgery, Long course concurrent chemoradiation with capecitabine and radiotherapy and Short course radiotherapy in people with Adenocarcinoma of the Rectum, run by University of Birmingham at 5 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Belgium, Denmark, Netherlands, Sweden, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase II (Feasibility study) Primary Outcome: Recruitment Rate (time frame: 24 Months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02945566, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2026.