Clinical Trial: NCT02945566 - My Cancer Genome

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

URL:

https://clinicaltrials.gov/show/NCT02945566

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

Drug	Synonyms	Arms
Long course concurrent chemoradiation		Long course concurrent chemoradiation

Purpose

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

Name	Type	Description	Interventions
Standard TME surgery	Active Comparator	Radical total mesorectal excision
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.	Long course concurrent chemoradiation
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.

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

May 31, 2018

Clinical Trials /

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