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

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ClinicalTrials.gov Identifier: NCT02945566
Recruitment Status : Recruiting
First Posted : October 26, 2016
Last Update Posted : May 31, 2018
Sponsor:
Information provided by (Responsible Party):
University of Birmingham

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.


Condition or disease Intervention/treatment Phase
Adenocarcinoma of the Rectum Procedure: Standard TME surgery Drug: Long course concurrent chemoradiation Radiation: Short course radiotherapy Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
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
Actual Study Start Date : June 14, 2017
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : October 2021

Arm Intervention/treatment
Active Comparator: Standard TME surgery
Radical total mesorectal excision
Procedure: Standard TME surgery
Total mesorectal excision

Experimental: 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.
Drug: 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.

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




Primary Outcome Measures :
  1. Year 1: randomise at least 4 cases per month internationally [ Time Frame: 1 years ]
    randomise at least 4 cases per month internationally (n=48)

  2. Year 2: randomise at least 6 cases per month internationally [ Time Frame: 2 years ]
    randomise at least 6 cases per month internationally (n=72)


Secondary Outcome Measures :
  1. Achieve funding from international partners [ Time Frame: 1 year ]
    assessed through seeing whether the study being carried out internationally

  2. Achieve recruitment from international partners [ Time Frame: 1 year ]
    assessed through seeing whether the study being carried out internationally

  3. Organ saving rate in the experimental arms at 12 months (from randomisation) [ Time Frame: 1 year ]
    Percent of relevant organs saved during 12 months

  4. Number of eligible patients undergoing accurately staged TME surgery [ Time Frame: 2 years ]
    Proportion of eligible patients undergoing accurately staged TME surgery

  5. Number of patients identified by MRI suitable for active monitoring based on mrTRG assessment [ Time Frame: 2 years ]
    Proportion of patients identified by MRI suitable for active monitoring based on mrTRG assessment

  6. 3 year pelvic failure rate [ Time Frame: 3 years ]

    defined as the proportion of patients in each arm with:

    1. unresectable pelvic tumor
    2. pelvic tumour requiring beyond TME surgery
    3. ≤1mm circumferential resection margin after TME surgery

  7. Overall survival [ Time Frame: 3 years ]
    Absence of death

  8. Stoma free survival [ Time Frame: 1 year ]
    Time for randomisation without the need for a stoma

  9. Health related quality of life by EORTC CR29 [ Time Frame: 2 years ]
    Assessed by EORTC CR29 score

  10. Health related quality of life by EORTC CR30 [ Time Frame: 2 years ]
    Assessed by EORTC CR30 score

  11. Health related quality of life by EQ-5D score [ Time Frame: 2 years ]
    Assessed by EQ-5D

  12. Sexual dysfunction [ Time Frame: 2 years ]
    Measured by LARS

  13. Bowel function [ Time Frame: 2 years ]
    Measured by LARS

  14. Bladder function [ Time Frame: 2 years ]
    Measured by LARS

  15. Sexual dysfunction in male patients [ Time Frame: 2 years ]
    Measured by ICICQ-MLUTS

  16. Bowel function in male patients [ Time Frame: 2 years ]
    Measured by ICICQ-MLUTS

  17. Bladder function in male patients [ Time Frame: 2 years ]
    Measured by ICICQ-MLUTS

  18. Sexual dysfunction in female patients [ Time Frame: 2 years ]
    Measured by ICICQ-FLUTS

  19. Bowel function in female patients [ Time Frame: 2 years ]
    Measured by ICICQ-FLUTS

  20. Bladder function in female patients [ Time Frame: 2 years ]
    Measured by ICICQ-FLUTS



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02945566


Contacts
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Contact: Manjinder Kaur 0121 415 9104 m.kaur@bham.ac.uk
Contact: Laura MaGill, PhD 01214159105 e.l.magill@bham.ac.uk

Locations
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Denmark
Odense University Hospital Recruiting
Odense, Denmark
Contact: Gunnar Baatrup, Prof         
Netherlands
Radboud University medical center Recruiting
Nijmegen, Netherlands
Contact: Hans de Wilt, Prof         
United Kingdom
University of Birmingham Recruiting
Birmingham, United Kingdom, B15 2TT
Contact: Simon Bach, MD    01213718170    s.p.bach@bham.ac.uk   
Sponsors and Collaborators
University of Birmingham
Investigators
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Principal Investigator: Simon Bach, MD University Hospitals Birmingham

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Birmingham
ClinicalTrials.gov Identifier: NCT02945566     History of Changes
Other Study ID Numbers: RG_15-011
2016-000862-49 ( EudraCT Number )
First Posted: October 26, 2016    Key Record Dates
Last Update Posted: May 31, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Adenocarcinoma
Rectal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases