Clinical Trials /

Can the Rectum be Saved by Watchful Waiting or TransAnal Surgery Following (Chemo)Radiotherapy Versus Total Mesorectal Excision for Early REctal Cancer?

NCT02945566

Description:

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.

Related Conditions:
  • Rectal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Can the Rectum be Saved by Watchful Waiting or TransAnal Surgery Following (Chemo)Radiotherapy Versus Total Mesorectal Excision for Early REctal Cancer?
  • 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

Clinical Trial IDs

  • ORG STUDY ID: RG_15-011
  • SECONDARY ID: 2016-000862-49
  • NCT ID: NCT02945566

Conditions

  • Adenocarcinoma of the Rectum

Interventions

DrugSynonymsArms
Long course concurrent chemoradiationLong course concurrent chemoradiation

Purpose

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:

        1. Standard TME surgery (control)

        2. Organ saving using:

             1. long course concurrent chemoradiation

             2. 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.
    

Trial Arms

NameTypeDescriptionInterventions
Standard TME surgeryActive ComparatorRadical total mesorectal excision
    Long course concurrent chemoradiationExperimentalCapecitabine: 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.
    • Long course concurrent chemoradiation
    Short course radiotherapyExperimentalA dose of 25Gy, applied, to the primary tumour and surrounding mesorectum in 5 fractions of 5 Gy, 5 days a week.

      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
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:16 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Year 1: randomise at least 4 cases per month internationally
      Time Frame:1 years
      Safety Issue:
      Description:randomise at least 4 cases per month internationally (n=48)

      Secondary Outcome Measures

      Measure:Achieve funding from international partners
      Time Frame:1 year
      Safety Issue:
      Description:assessed through seeing whether the study being carried out internationally
      Measure:Achieve recruitment from international partners
      Time Frame:1 year
      Safety Issue:
      Description:assessed through seeing whether the study being carried out internationally
      Measure:Organ saving rate in the experimental arms at 12 months (from randomisation)
      Time Frame:1 year
      Safety Issue:
      Description:Percent of relevant organs saved during 12 months
      Measure:Number of eligible patients undergoing accurately staged TME surgery
      Time Frame:2 years
      Safety Issue:
      Description:Proportion of eligible patients undergoing accurately staged TME surgery
      Measure:Number of patients identified by MRI suitable for active monitoring based on mrTRG assessment
      Time Frame:2 years
      Safety Issue:
      Description:Proportion of patients identified by MRI suitable for active monitoring based on mrTRG assessment
      Measure:3 year pelvic failure rate
      Time Frame:3 years
      Safety Issue:
      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
      Measure:Overall survival
      Time Frame:3 years
      Safety Issue:
      Description:Absence of death
      Measure:Stoma free survival
      Time Frame:1 year
      Safety Issue:
      Description:Time for randomisation without the need for a stoma
      Measure:Health related quality of life by EORTC CR29
      Time Frame:2 years
      Safety Issue:
      Description:Assessed by EORTC CR29 score
      Measure:Health related quality of life by EORTC CR30
      Time Frame:2 years
      Safety Issue:
      Description:Assessed by EORTC CR30 score
      Measure:Health related quality of life by EQ-5D score
      Time Frame:2 years
      Safety Issue:
      Description:Assessed by EQ-5D
      Measure:Sexual dysfunction
      Time Frame:2 years
      Safety Issue:
      Description:Measured by LARS
      Measure:Bowel function
      Time Frame:2 years
      Safety Issue:
      Description:Measured by LARS
      Measure:Bladder function
      Time Frame:2 years
      Safety Issue:
      Description:Measured by LARS
      Measure:Sexual dysfunction in male patients
      Time Frame:2 years
      Safety Issue:
      Description:Measured by ICICQ-MLUTS
      Measure:Bowel function in male patients
      Time Frame:2 years
      Safety Issue:
      Description:Measured by ICICQ-MLUTS
      Measure:Bladder function in male patients
      Time Frame:2 years
      Safety Issue:
      Description:Measured by ICICQ-MLUTS
      Measure:Sexual dysfunction in female patients
      Time Frame:2 years
      Safety Issue:
      Description:Measured by ICICQ-FLUTS
      Measure:Bowel function in female patients
      Time Frame:2 years
      Safety Issue:
      Description:Measured by ICICQ-FLUTS
      Measure:Bladder function in female patients
      Time Frame:2 years
      Safety Issue:
      Description:Measured by ICICQ-FLUTS

      Details

      Phase:Phase 2
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:University of Birmingham

      Last Updated