Back to resultsCan the Rectum be Saved by Watchful Waiting or TransAnal Surgery Following (Chemo)Radiotherapy Versus Total Mesorectal Excision for Early REctal Cancer? (STAR-TREC)
Primary Purpose
Adenocarcinoma of the Rectum
Status
Unknown status
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Standard TME surgery
Long course concurrent chemoradiation
Short course radiotherapy
Sponsored by
About this trial
This is an interventional other trial for Adenocarcinoma of the Rectum
Eligibility Criteria
Inclusion Criteria:
- Biopsy proven adenocarcinoma of the rectum
- 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)
MDT determines that all of the following treatment options are feasible:
- TME surgery
- CRT
- SCPRT
- TEM Patients with equivocal radiological lesions e.g. mesorectal, retroperitoneal, liver, lung are eligible if agreed by MDT
- Aged 16 or over in UK (18 or over in the Netherlands and Denmark).
Pre-(chemo)radiotherapy treatment, the following criteria must be met :
- Estimated creatinine clearance >50 mls/min -Absolute neutrophil count >1.5x109/l; platelets >100 x 109/L-
- Serum transaminase <3 x Upper Limit Normal/l (ULN)
- Bilirubin <1.5 x ULN
- ECOG performance status 0-1
If female and of childbearing potential, must:
- Have a negative pregnancy test ≤72hours prior to initiating study treatment
- Agree to avoid pregnancy during and for 6 months after study treatment
If male with a partner of childbearing potential, must:
- Agree to use adequate, medically approved, contraceptive precautions during and for 90 days after the last dose of study treatment
- Patient able and willing to provide written informed consent for the study
Exclusion Criteria:
- Unequivocal evidence of metastatic disease (includes resectable metastases) as determined by
MRI showing:
- node positive
- extramural vascular invasion (mriEMVI) positive
- defined mucinous tumour
- Maximum tumour diameter > 40mm as measured from everted edges (sagittal)
- Mesorectal fascia threatened (< 1 mm on MRI)
- 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 within 6 months prior to randomisation)
- Known dihydropyrimidine dehydrogenase (DPYD) deficiency
- Known Gilberts disease (hyperbilirubinaemia)
- Taking warfarin that cannot be discontinued at least 7 days prior to starting treatment or substituted by low molecular weight heparin
Sites / Locations
- Odense University HospitalRecruiting
- Radboud University medical centerRecruiting
- University of BirminghamRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Experimental
Experimental
Arm Label
Standard TME surgery
Long course concurrent chemoradiation
Short course radiotherapy
Arm Description
Radical total mesorectal excision
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.
A dose of 25Gy, applied, to the primary tumour and surrounding mesorectum in 5 fractions of 5 Gy, 5 days a week.
Outcomes
Primary Outcome Measures
Year 1: randomise at least 4 cases per month internationally
randomise at least 4 cases per month internationally (n=48)
Year 2: randomise at least 6 cases per month internationally
randomise at least 6 cases per month internationally (n=72)
Secondary Outcome Measures
Achieve funding from international partners
assessed through seeing whether the study being carried out internationally
Achieve recruitment from international partners
assessed through seeing whether the study being carried out internationally
Organ saving rate in the experimental arms at 12 months (from randomisation)
Percent of relevant organs saved during 12 months
Number of eligible patients undergoing accurately staged TME surgery
Proportion of eligible patients undergoing accurately staged TME surgery
Number of patients identified by MRI suitable for active monitoring based on mrTRG assessment
Proportion of patients identified by MRI suitable for active monitoring based on mrTRG assessment
3 year pelvic failure rate
defined as the proportion of patients in each arm with:
unresectable pelvic tumor
pelvic tumour requiring beyond TME surgery
≤1mm circumferential resection margin after TME surgery
Overall survival
Absence of death
Stoma free survival
Time for randomisation without the need for a stoma
Health related quality of life by EORTC CR29
Assessed by EORTC CR29 score
Health related quality of life by EORTC CR30
Assessed by EORTC CR30 score
Health related quality of life by EQ-5D score
Assessed by EQ-5D
Sexual dysfunction
Measured by LARS
Bowel function
Measured by LARS
Bladder function
Measured by LARS
Sexual dysfunction in male patients
Measured by ICICQ-MLUTS
Bowel function in male patients
Measured by ICICQ-MLUTS
Bladder function in male patients
Measured by ICICQ-MLUTS
Sexual dysfunction in female patients
Measured by ICICQ-FLUTS
Bowel function in female patients
Measured by ICICQ-FLUTS
Bladder function in female patients
Measured by ICICQ-FLUTS
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02945566
Brief Title
Can the Rectum be Saved by Watchful Waiting or TransAnal Surgery Following (Chemo)Radiotherapy Versus Total Mesorectal Excision for Early REctal Cancer?
Acronym
STAR-TREC
Official Title
STAR-TREC:Can the Rectum be Saved by Watchful Waiting or TransAnal Surgery Following (Chemo)Radiotherapy Versus Total Mesorectal Excision for Early REctal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
May 2018
Overall Recruitment Status
Unknown status
Study Start Date
June 14, 2017 (Actual)
Primary Completion Date
October 2021 (Anticipated)
Study Completion Date
October 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Birmingham
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Colorectal cancer is the third most common tumour in the UK, Netherlands and Denmark with 41000, 14000 and 4000 new cases per year respectively. 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 5-10% 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.
TREC was a randomised phase II trial to test the feasibility of randomisation between TME and an organ preserving policy of short course pre-operative radiotherapy (SCPRT) delay followed by transanal endoscopic microsurgery (TEM). STAR-TREC is a phase II feasibility study that will evaluate whether it is possible to accelerate the patient recruitment attained in the TREC study, to 4 per month in the first year of recruitment and 6 per month in the second. This would demonstrate deliverability of a phase III study.
Detailed Description
STAR-TREC is a randomised, three arm (1:1:1) study using the following arms:
Standard TME surgery (control)
Organ saving using:
long course concurrent chemoradiation
short course radiotherapy For organ-preserving strategies clinical response to radiotherapy determines the next treatment step. Radiotherapy response is evaluated using endoscopy and the tumour regression grade, as assessed by MRI. The first assessment at 11-13 weeks (from radiotherapy start) using MRI and endoscopy 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 determines if the STAR-TREC criteria for complete clinical response (cCR) are met. Patients who achieve cCR may progress directly to active surveillance. Those who do not fulfil the criteria for cCR will progress to excision biopsy with transanal endoscopic microsurgery (TEM).
Patients in the organ saving arm will be assigned to either;
A. Long course concurrent chemoradiation:
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.
or B. Short course preoperative radiotherapy A dose of 25Gy, applied, to the primary tumour and surrounding mesorectum in 5 fractions of 5 Gy, 5 days a week.
As a feasibility study, this trial will have recruitment rate as it's primary outcome.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenocarcinoma of the Rectum
7. Study Design
Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Standard TME surgery
Arm Type
Active Comparator
Arm Description
Radical total mesorectal excision
Arm Title
Long course concurrent chemoradiation
Arm Type
Experimental
Arm Description
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.
Arm Title
Short course radiotherapy
Arm Type
Experimental
Arm Description
A dose of 25Gy, applied, to the primary tumour and surrounding mesorectum in 5 fractions of 5 Gy, 5 days a week.
Intervention Type
Procedure
Intervention Name(s)
Standard TME surgery
Intervention Description
Total mesorectal excision
Intervention Type
Drug
Intervention Name(s)
Long course concurrent chemoradiation
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
Short course radiotherapy
Intervention Description
A dose of 25Gy, applied, to the primary tumour and surrounding mesorectum in 5 fractions of 5 Gy, 5 days a week.
Primary Outcome Measure Information:
Title
Year 1: randomise at least 4 cases per month internationally
Description
randomise at least 4 cases per month internationally (n=48)
Time Frame
1 years
Title
Year 2: randomise at least 6 cases per month internationally
Description
randomise at least 6 cases per month internationally (n=72)
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Achieve funding from international partners
Description
assessed through seeing whether the study being carried out internationally
Time Frame
1 year
Title
Achieve recruitment from international partners
Description
assessed through seeing whether the study being carried out internationally
Time Frame
1 year
Title
Organ saving rate in the experimental arms at 12 months (from randomisation)
Description
Percent of relevant organs saved during 12 months
Time Frame
1 year
Title
Number of eligible patients undergoing accurately staged TME surgery
Description
Proportion of eligible patients undergoing accurately staged TME surgery
Time Frame
2 years
Title
Number of patients identified by MRI suitable for active monitoring based on mrTRG assessment
Description
Proportion of patients identified by MRI suitable for active monitoring based on mrTRG assessment
Time Frame
2 years
Title
3 year pelvic failure rate
Description
defined as the proportion of patients in each arm with:
unresectable pelvic tumor
pelvic tumour requiring beyond TME surgery
≤1mm circumferential resection margin after TME surgery
Time Frame
3 years
Title
Overall survival
Description
Absence of death
Time Frame
3 years
Title
Stoma free survival
Description
Time for randomisation without the need for a stoma
Time Frame
1 year
Title
Health related quality of life by EORTC CR29
Description
Assessed by EORTC CR29 score
Time Frame
2 years
Title
Health related quality of life by EORTC CR30
Description
Assessed by EORTC CR30 score
Time Frame
2 years
Title
Health related quality of life by EQ-5D score
Description
Assessed by EQ-5D
Time Frame
2 years
Title
Sexual dysfunction
Description
Measured by LARS
Time Frame
2 years
Title
Bowel function
Description
Measured by LARS
Time Frame
2 years
Title
Bladder function
Description
Measured by LARS
Time Frame
2 years
Title
Sexual dysfunction in male patients
Description
Measured by ICICQ-MLUTS
Time Frame
2 years
Title
Bowel function in male patients
Description
Measured by ICICQ-MLUTS
Time Frame
2 years
Title
Bladder function in male patients
Description
Measured by ICICQ-MLUTS
Time Frame
2 years
Title
Sexual dysfunction in female patients
Description
Measured by ICICQ-FLUTS
Time Frame
2 years
Title
Bowel function in female patients
Description
Measured by ICICQ-FLUTS
Time Frame
2 years
Title
Bladder function in female patients
Description
Measured by ICICQ-FLUTS
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Biopsy proven adenocarcinoma of the rectum
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)
MDT determines that all of the following treatment options are feasible:
TME surgery
CRT
SCPRT
TEM Patients with equivocal radiological lesions e.g. mesorectal, retroperitoneal, liver, lung are eligible if agreed by MDT
Aged 16 or over in UK (18 or over in the Netherlands and Denmark).
Pre-(chemo)radiotherapy treatment, the following criteria must be met :
Estimated creatinine clearance >50 mls/min -Absolute neutrophil count >1.5x109/l; platelets >100 x 109/L-
Serum transaminase <3 x Upper Limit Normal/l (ULN)
Bilirubin <1.5 x ULN
ECOG performance status 0-1
If female and of childbearing potential, must:
Have a negative pregnancy test ≤72hours prior to initiating study treatment
Agree to avoid pregnancy during and for 6 months after study treatment
If male with a partner of childbearing potential, must:
Agree to use adequate, medically approved, contraceptive precautions during and for 90 days after the last dose of study treatment
Patient able and willing to provide written informed consent for the study
Exclusion Criteria:
Unequivocal evidence of metastatic disease (includes resectable metastases) as determined by
MRI showing:
node positive
extramural vascular invasion (mriEMVI) positive
defined mucinous tumour
Maximum tumour diameter > 40mm as measured from everted edges (sagittal)
Mesorectal fascia threatened (< 1 mm on MRI)
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 within 6 months prior to randomisation)
Known dihydropyrimidine dehydrogenase (DPYD) deficiency
Known Gilberts disease (hyperbilirubinaemia)
Taking warfarin that cannot be discontinued at least 7 days prior to starting treatment or substituted by low molecular weight heparin
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Manjinder Kaur
Phone
0121 415 9104
Email
m.kaur@bham.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
Laura MaGill, PhD
Phone
01214159105
Email
e.l.magill@bham.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Simon Bach, MD
Organizational Affiliation
University Hospitals Birmingham
Official's Role
Principal Investigator
Facility Information:
Facility Name
Odense University Hospital
City
Odense
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gunnar Baatrup, Prof
Facility Name
Radboud University medical center
City
Nijmegen
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hans de Wilt, Prof
Facility Name
University of Birmingham
City
Birmingham
ZIP/Postal Code
B15 2TT
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Simon Bach, MD
Phone
01213718170
Email
s.p.bach@bham.ac.uk
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32095545
Citation
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.
Results Reference
derived
PubMed Identifier
32070386
Citation
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.
Results Reference
derived
PubMed Identifier
29288190
Citation
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.
Results Reference
derived
Learn more about this trial
Can the Rectum be Saved by Watchful Waiting or TransAnal Surgery Following (Chemo)Radiotherapy Versus Total Mesorectal Excision for Early REctal Cancer?
We'll reach out to this number within 24 hrs