Can We Save the Rectum by Watchful Waiting or TransAnal Surgery Following (chemo)Radiotherapy Versus Total Mesorectal Excision for Early REctal Cancer?

NCT02945566 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: RG_15-0112016-000862-49
• Study Type: interventional
• Target: 380
• Locations: 5 countries
• Sites: 5

Brief 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. 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).

Conditions

Adenocarcinoma of the Rectum

Outcome Measures

Primary Outcomes (2)

• 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.

  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%.

  30 Months from start day of (chemo)radiotherapy treatment.

Secondary Outcomes (38)

• Phase II (Feasibility study): Core Endpoint - Funding

  12 Months

• Phase II (Feasibility study): Core Endpoint - International Recruitment

  12 Months

• Phase II (Feasibility study): Core Endpoint - Efficacy

  12 Months

• Phase II: Safety- Accuracy of MRI in predicting STAR-TREC eligibility

  24 Months

• Phase II: Safety - 30 day Mortality

  30 days

Study Arms (3)

Standard TME surgery

ACTIVE COMPARATOR

Radical total mesorectal excision

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.

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.

Radiation: Short course radiotherapy

Interventions

Standard TME surgery PROCEDURE

Total mesorectal excision

Standard TME surgery

Long course concurrent chemoradiation with capecitabine and radiotherapy DRUG

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.

Also known as: Xeloda is the brand name for capecitabine

Long course concurrent chemoradiation

Short course radiotherapy RADIATION

A dose of 25Gy, applied, to the primary tumour and surrounding mesorectum in 5 fractions of 5 Gy, 5 days a week.

Short course radiotherapy

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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)
• 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)

Sponsors & Collaborators

• University of Birmingham: lead

Study Sites (5)

University Hospital UZ Leuven

Leuven, Belgium

Location

Odense University Hospital

Odense, Denmark

Location

Radboud University medical center

Nijmegen, Netherlands

Location

Region Stockholm, Onkologkliniken Södersjukhuset AB

Stockholm, Sweden

Location

University of Birmingham

Birmingham, B15 2TT, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 37310167 DERIVED

• Appelt 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.

  PMID: 32095545 DERIVED

• van 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.

  PMID: 32070386 DERIVED

• Rombouts 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.

  PMID: 29288190 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Capecitabine; Radiotherapy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Therapeutics

Study Officials

• Simon Bach, MD

  University Hospitals Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2016
• First Posted: October 26, 2016
• Study Start: June 14, 2017
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): August 1, 2028
• Last Updated: March 27, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1); DK (1); NL (1); BE (1); GB (1)