STAR-TREC: Can we Save the rectum by watchful waiting or TransAnal surgery following (chemo)Radiotherapy versus Total mesorectal excision for early REctal Cancer?

Overview

Sponsor-declared trial summary

Key facts

Sponsor

The University Of Birmingham

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

16 Jun 2017 → ongoing

Decision date (initial)

2024-11-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

KWF Dutch Cancer Society · Kom Op Tegen Kanker · Cancerfonden 22 2052 S · Cancer Research UK

External identifiers

EU CT number

2024-516106-31-00

EudraCT number

2016-000862-49

ISRCTN

ISRCTN14240288

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The phase II component will assess the feasibility of a large, multi-centre randomised trial comparing radical surgery versus organ saving treatment using (chemo)radiotherapy followed by selective transanal microsurgery.

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:
a) Determine the optimal radiation schedule to achieve the highest rate of organ preservation
b) Determine the optimal radiation schedule to achieve the best quality of life after organ preservation

Secondary objectives 17

1. Phase II - 1. Year 1: Can one international partner procure independent STAR-TREC funding? Successful international collaboration will be necessary to deliver a future phase III study of 400 patients.
2. Phase II - 2. Year 1: Can one international partner open the STAR-TREC study to recruitment?
3. Phase II - 3. Efficacy of organ preserving treatment arms on completion of phase II study: Is the organ saving rate > 50% at 12 months (following randomisation) in the experimental arms? This figure is intended as a guide to both the STARTREC DMC and any phase III peer review.
4. Phase II - 4. Proportion of patients undergoing primary TME surgery (control-group) accurately staged by MRI and satisfying STAR-TREC inclusion/ exclusion criteria. We will report the accuracy of MRI based patient selection, compared to the reference standard of post-operative histological staging.
5. Phase II - 5. Estimate accuracy of MRI assessment for prediction of tumour response to radiotherapy in the organ saving (experimental) group. We will report the proportion of patients reported as achieving ‘satisfactory’ versus ‘poor’ tumour response following radiotherapy treatment, based upon assessment of the MRI tumour regression grade (mrTRG). We will also report correlation between mrTRG and histopathological stage for subjects who progress to surgery following radiotherapy; either transanal micosurgery or radical TME.
6. Phase II - 6. Pelvic failure rate associated with organ saving treatment versus primary TME surgery at 3 years. We consider that organ saving treatment has failed when a tumour recurrence or tumour regrowth is not satisfactorily treated by TME surgery.
7. Phase II - 7. Overall survival rate at 3 years associated with organ saving treatment versus primary TME surgery at 3 years.
8. Phase II - 8. Proportion of patients (in each group) with a stoma at 30 days and 12 months.
9. Phase II - 9. Health Related Quality of Life (HR QoL) measured by EORTC QLQ CR29 & C30, EuroQoL EQ-5D (baseline and 12, 24 months post randomisation).
10. Phase II - 10. Bowel, bladder and sexual dysfunction measured by LARS score and ICIQ-MLUTS (baseline and 12, 24 months post randomisation).
11. Phase III - 1. Demonstrate efficacy and low toxicity of mesorectal radiation fields for treatment of early rectal cancer.
12. Phase III - 2. Establish safety of mesorectal radiation and selective transanal microsurgical excision for organ preservation in early rectal cancer.
13. Phase III - 3. Introduce standardised scheme for evaluation and interpretation of clinical response to (chemo)radiation treatment in early stage rectal cancer.
14. Phase III - 4. Establish the safety and efficacy of non-operative management of CR in the context of early rectal cancer treatment.
15. Phase III - 5.Compare the toxicity and quality of life outcomes for patients undergoing standard TME surgery with those who receive organ-preserving treatments.
16. Phase III - 6.Investigate the potential of genomic markers in blood (ctDNA), associated with persistence of tumour tissue, to facilitate the selection of patients for an organ saving approach based upon the likelihood of treatment success.
17. Phase III - 7.Evaluate the utility of ctDNA for determination of partial versus complete response, and thereby the decision to perform local transanal excision.

Conditions and MedDRA coding

Early stage colorectal cancer

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Biopsy proven adenocarcinoma of the rectum
2. Magnetic Resonance Imaging (MRI)- or Endorectal Ultrasound (ERUS)-staged TX/T1-3b, NX/N0, MX/M0 rectal tumour
3. MDT determines that the following treatment options are all reasonable and feasible: (a) TME surgery, (b) CRT, (c) SCRT and (d) Transanal Endoscopic Microsurgery (TEM)
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
5. Willing and able to consent

Exclusion criteria 17

1. 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
2. MRI node positive (≥N1, defined by protocol guidelines)
3. MRI extramural vascular invasion (mriEMVI) present (defined by protocol guidelines)
4. MRI defined mucinous tumour
5. Mesorectal fascia threatened by tumour (≤ 1mm on MRI or ERUS)
6. Maximum tumour diameter >40mm (either measured from everted edges on sagittal MRI or ERUS examination)
7. Anterior tumour location above the peritoneal reflection on MRI or ERUS
8. No residual luminal tumour following endoscopic mucosal resection
9. Prior pelvic radiotherapy
10. Definite evidence of regional or distant metastases (M1) in opinion of MDT
11. Uncontrolled cardiorespiratory comorbidity (inadequately controlled angina or myocardial infarction or arrhythmia within 6 months prior to trial entry)
12. Known complete Dihydropyrimidine Dehydrogenase deficiency
13. Known Gilbert’s disease
14. Taking coumarin-derivative oral anticoagulants that cannot be stopped or substituted by low molecular weight heparin
15. Taking metronidazole, phenytoin, sorivudine or its analogues, such as brivudine
16. Women who are pregnant or lactating
17. Age <16 years (UK), <18 years (other countries)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase II: The primary endpoint of the STAR-TREC feasibility study is - Recruitment rate measured at 12 and 24 months.
2. Phase III: 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.

Secondary endpoints 20

1. A) Secondary outcomes for the randomised comparison between organ-preserving strategies:
2. * Clinician-reported acute treatment-related toxicity up to 30 days following completion of (chemo)radiotherapy
3. * Proportion of patients with complete response to (chemo)radiation therapy
4. * Proportion of patients undergoing transanal local excision
5. * Time to event of organ loss assessed for patients who prefer organ preservation; defined as the length of time from the start date of trial treatment until TME surgery
6. * 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
7. * 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
8. * 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
9. * Overall survival to 60 months; defined as the length of time from the start date of trial treatment until death (any cause)
10. B) Secondary endpoints for analyses incorporating the standard surgery comparator (phase II: randomised comparison; phase III: non-randomised comparison):
11. * Clinician-reported acute treatment related toxicity up to 30 days following completion of (chemo)radiotherapy or date of initial surgery
12. * Non-regrowth pelvic tumour control 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 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
13. * 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
14. * 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
15. * 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)
16. * Decision regret at 24 months measured using the validated Decision regret scale questionnaire
17. C) Secondary endpoints for analyses of patient-reported outcomes
18. * Symptomatic toxicity, health economics and HRQoL measured at 3, 12, 24 and 36 months compared to baseline using validated questionnaires (HRQoL booklet) This analysis will be conducted incorporating the following comparisons:
19. a. Randomised comparison between organ-preserving strategies
20. b. Randomised (phase II data) and non-randomised (phase III data) comparisons between organ preserving strategies and the standard surgery comparator

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

The University Of Birmingham

Sponsor organisation

The University Of Birmingham

Address

Vincent Drive

City

Birmingham

Postcode

B15 2TT

Country

United Kingdom

Scientific contact point

Organisation

The University Of Birmingham

Contact name

Clinical Trial Coordinator

Public contact point

Organisation

The University Of Birmingham

Contact name

Clinical Trial Coordinator

Locations

3 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications