Pre-therapeutic MRI Assessment of Early Stage Rectal Cancer and Significant Rectal Polyps to Avoid Major Resectional Surgery: A New Approach to the Management of Early Stage Rectal Cancer. (PRESERVE)

This multicentre, prospective, randomised, feasibility trial aims to change UK practice by enabling more patients with early rectal cancer to safely undergo local excision rather than major surgery thus maintaining quality of life without compromising survival outcomes.

Study Overview

• Status: Not yet recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Other: Surveillance 6 monthly; Other: Radiotherapy and surveillance; Other: surveillance 3 montly

Detailed Description

The national bowel cancer screening programme (BCSP) has shown an increase in detection rates of early rectal cancer (ERC). This is treated effectively with radical surgery, offering excellent oncological outcome, but has a major impact on patient quality of life. The diagnosis of early stage rectal cancer, allows an opportunity for effective oncological treatment, with preservation of the rectum avoiding the deleterious effects of unselective use of radical surgery and unselected use of radiotherapy. Our previous work has led to High-Spatial-Resolution magnetic resonance imaging (MRI) as the established modality for providing reliable information about extramural disease prior to radical surgery.

This trial will use a new MRI staging protocol to identify more patients with early rectal cancer to enable accurate mapping for more precise patient selection for local excision. Improved success with local excision will result in greater rates of organ preservation.

• Study Type: Interventional
• Enrollment (Anticipated): 146
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gina Brown; Phone Number: +442086613964; Email: gina.brown@rmh.nhs.uk
• Study Contact Backup: Name: Xian van Gelder; Phone Number: 4344 +442086426011; Email: xian.vangelder@rmh.nhs.uk

Study Locations

• United Kingdom
  • London
    • Chelsea, London, United Kingdom, SW3 6JJ
      • The Royal Marsden NHSHFT
      • Principal Investigator: Gina Brown
      • Contact: Gina Brown; Phone Number: +442086613964; Email: gina.brown@rmh.nhs.uk
      • Contact: Xian van Gelder; Phone Number: 4344 +442086426011; Email: xian.vangelder@rmh.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• mrT3b tumour or less on initial assessment
• Absence of mrEMVI / mrN1c deposits
• mrCRM clear >1mm
• Rectal lesion as defined on MRI/Endoscopy. (If patients are registered at endoscopy and later found, on MRI, not to have a rectal ERC, they should be withdrawn from the study)
• Over 18 years of age
• Of adequate performance status to be able to undergo surgery if necessary

Exclusion Criteria:

• are requiring neoadjuvant therapy for MRI-staged advanced rectal cancer
• have metastatic disease
• have a second malignancy where there is <95% certainty of survival from the treated disease
• are unable to consent or withhold consent
• have biopsy-proven malignancy which is not adenocarcinoma (Patients do not need to have had a biopsy prior to registration. However, if after excision the ERC is found to either not be an adenocarcinoma or be benign, the patient should be withdrawn from the study.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Low risk; MR Staged >1mm muscularis preserved and technically feasible to perform local excision. Pathology assessment on sample with confirmation of adenocarcinoma. Sample assessed to be low risk based on PRESERVE Risk Score of 0. (Margin Clear >0mm from the diathermy margin and Sm1/2 or Haggitt 1/2/3) Six monthly follow up from date of surgery.	Other: Surveillance 6 monthly; 6 monthly surveillance
Active Comparator: Moderate Risk - RT&Surveillance; MR Staged >1mm muscularis preserved and technically feasible to perform local excision. Pathology assessment on sample with confirmation of adenocarcinoma. Sample assessed to be low risk based on PRESERVE Risk Score of 1. (Margin positive -0mm to the diathermy margin, or SM3 or Haggitt 4, or LVI) Patient randomized to receive radiotherapy (RT) and regular surveillance, with 3 monthly follow-up from the date of surgery.	Other: Radiotherapy and surveillance; as per local policy
Active Comparator: Moderate Risk - Surveillance; MR Staged >1mm muscularis preserved and technically feasible to perform local excision. Pathology assessment on sample with confirmation of adenocarcinoma. Sample assessed to be low risk based on PRESERVE Risk Score of 1. (Margin positive -0mm to the diathermy margin, or SM3 or Haggitt 4, or LVI) Patient randomized to surveillance arm with regular surveillance, with 3 monthly follow-up from the date of surgery.	Other: surveillance 3 montly; 3 monthly surveillance
Active Comparator: High Risk; MR Staged >1mm muscularis preserved and technically feasible to perform local excision. Pathology assessment on sample with confirmation of adenocarcinoma. Sample assessed to be low risk based on PRESERVE Risk Score of >2. (Margin positive - 0mm to the diathermy margin, Margin positive/or unassessable due to piecemeal removal - 0mm to the tumour margin, Sm3 or Haggitt 4, Poorly differentiated/mucinous, LVI, T2) Patient is considered for surgery, receives radiotherapy and surveillance, with 3 monthly follow-up from date of surgery.	Other: Radiotherapy and surveillance; as per local policy
Active Comparator: TME (Total mesorectal excision) Surgery; For patients where it is considered technically feasible to do LE but MR staged<1mm muscularis preserved, or it is considered not feasible to perform a local excision. Patients undergo TME surgery. Pathology assessment on sample with confirmation of adenocarcinoma. Patient receives 6 monthly follow-up from date of surgery.	Other: Surveillance 6 monthly; 6 monthly surveillance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Demonstrate a change in rectal preservation rates	Demonstrate a change in rectal preservation rates in patients with pT1 and pT2 tumours.	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To measure the accuracy of MRI T staging when compared with pathology.	To measure the accuracy of MRI T staging when compared with pathology.	36 months
Rates of missed lesions for local excision	Report on rates of missed lesions suitable for local excision.	36 months
Rates of lesions not for local excision	Report on rates of lesions not feasible for local excision	36 months
Cost comparison	Compare costs to the NHS/other healthcare systems of major surgery versus local excision for pT1/T2 ERC.	36 months
Measure impact on patient quality of life	Measure impacts of local excision and rectal preservation on patient reported quality of life outcome measures compared with stage matched patients undergoing major surgery due to patient choice or technical inability to undertake locale scission. Measurement tools used for assessment are the LARS (low anterior resection syndrome) score, the EQ-5D and Stoma Care Quality of Life Questionnaire.	36 months
Measure relapse-free rates at 1 year post surgery / local excision.	Put in a separate point saying: Measure survival rates at 1 year post surgery / local excision.	36 months
Assess the quality of local excision surgery	To assess the quality of local excision surgery, using review of pathology slides and reports, commenting on completeness of excision, excision margins and en bloc manner of resection (local excision specimens).	36 months
Assess patient willingness to be randomised	Assess patient willingness to be randomised by qualitative questionnaire	36 months

Collaborators and Investigators

• Sponsor: Royal Marsden NHS Foundation Trust
• Collaborators: Pelican Cancer Foundation

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2019
• Primary Completion (Anticipated): April 1, 2032
• Study Completion (Anticipated): April 1, 2032

Study Registration Dates

• First Submitted: September 5, 2019
• First Submitted That Met QC Criteria: September 23, 2019
• First Posted (Actual): September 25, 2019

Study Record Updates

• Last Update Posted (Actual): September 25, 2019
• Last Update Submitted That Met QC Criteria: September 23, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: early stage; early phase
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: CCR 4993

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No