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Avoiding Surgery in Rectal Cancer After Pre-Operative Therapy

Primary Purpose

Rectal Adenocarcinoma

Status

Unknown status

Phase

Phase 2

Locations

United Kingdom

Study Type

Interventional

Intervention

Adjuvant Chemotherapy

Surgery

About this trial

This is an interventional treatment trial for Rectal Adenocarcinoma focused on measuring locally invasive high-risk rectal adenocarcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age > 18 years
Locally invasive high-risk rectal adenocarcinoma as defined by the presence on MRI of at least one of the following: i) Tumours within 1mm of mesorectal fascia i.e. circumferential resection margin threatened or involved ii)T3 tumours at/below levators iii)Tumours extending ≥5mm into peri-rectal fat iv)T4 tumours (including the involvement of bladder or vagina if surgical resection is possible with clear margins) v)Presence of extra-mural venous invasion (primary tumour is therefore at least T3) vi)T2 N0/1/2 tumours requiring Abdomino-Perineal Excision, within 1mm of mesorectal fascia i.e. circumferential resection margin threatened or involved
The absence of malignant pelvic side-wall disease, local recurrence (either after TME or wide local excision) or metastatic disease
Completion of pre-operative long-course CRT
No viable disease seen at MRI performed 4 weeks after long-course CRT, confirmed at 8 week MRI
Evidence of partial response of rectal tumour to pre-operative long-course CRT at 4 week MRI which continues to show an incremental response at 8 week MRI.
Histological diagnosis of adenocarcinoma of rectum.
WHO performance status 0, 1 or 2.
No evidence of metastatic disease as determined by CT scan of chest, abdomen, pelvis or other investigations such as PET scan or biopsy if required.
Informed written consent

Exclusion Criteria:

Age < 18 years.
Absence of concomitant chemotherapy.
RT dose below 50Gy.
Stable disease at 4 week MRI.
Disease that demonstrates a partial response at 4 week MRI but shows no evidence of an incremental response at 8 week MRI.
Pregnancy or breast feeding
Short course pre-operative radiotherapy
Previous pelvic radiotherapy
Medical or psychiatric conditions that compromise the patient's ability to give informed consent
Any contra-indication to MRI scanning, eg Cardiac Pacemaker or Hip prosthesis.
Any patients within the EXPERT-C trial.
Tumours which are mucinous (>50% mucin seen on MRI), as these are more likely to be PET negative

Sites / Locations

Royal Marsden NHS Foundation Trust

Outcomes

Primary Outcome Measures

To estimate the percentage of patients who can safely omit surgery, defined as the percentage of patients at two years after end of CRT who have not had surgery and who are in CR (no detectable local disease)

To prove the safety of deferred surgery, as measured by the percentage of patients who have local failure at two years, where local failure is defined as positive margin status of resected tumour or surgically unsalvageable disease.

Secondary Outcome Measures

Time to distant disease

Time to maximal tumour response after CRT

Time to local re-growth

Percentages of positive margins, and sphincter-preservation rates in patients who have had surgery

Progression-free and overall survival

Quality of Life including long-term bowel, urinary and sexual function

To correlate the expression of biological markers which may predict for pathological complete response with progression free survival

Full Information

NCT ID

NCT01047969

First Posted

January 12, 2010

Last Updated

June 12, 2019

Sponsor

Royal Marsden NHS Foundation Trust

1. Study Identification

Unique Protocol Identification Number

NCT01047969

Brief Title

Avoiding Surgery in Rectal Cancer After Pre-Operative Therapy

Official Title

Non-Operative Treatment for Rectal Cancer Following Complete Response to Neo-Adjuvant Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

May 2016

Overall Recruitment Status

Unknown status

Study Start Date

June 6, 2006 (Actual)

Primary Completion Date

June 2019 (Anticipated)

Study Completion Date

June 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Royal Marsden NHS Foundation Trust

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The objective of Timing and Deferral of Rectal Surgery Following a Continued Response to Pre-operative CRT study is to establish the time to maximum tumour response following CRT, and to investigate whether surgery can be safely avoided within the tight framework of the trial follow-up protocol in a small group of patients where the cancer becomes undetectable by imaging modalities.

Detailed Description

The study uses MRI in combination with FDG-PET CT and clinical examination (tri-modality assessment) to assess for a continued incremental response to CRT. Surgery is NOT withheld from patients entering this study. Indeed, surgery is an option at each stage of patient follow-up and is a crucial component of a patient's treatment pathway should no further regression of disease be detected through stringent follow-up. If a status of 'no detectable disease' by serial MRI, CT-PET and clinical assessment is achieved and the patient wishes not to have surgery, they will continue to be carefully monitored within the framework of the trial follow-up protocol.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rectal Adenocarcinoma

Keywords

locally invasive high-risk rectal adenocarcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

99 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Adjuvant Chemotherapy

Intervention Description

If after MRI + FDG-PET 8 weeks post CRT the patient shows no visible tumour or further regression adjuvant chemotherapy will be considered.

Intervention Type

Procedure

Intervention Name(s)

Surgery

Intervention Description

If after MRI + FDG-PET 8 weeks post CRF no further regression or growth of disease occurs the patient will be referred for surgery.

Primary Outcome Measure Information:

Title

Time Frame

Two years post end of chemoradiotherapy

Title

Time Frame

Two years post end of chemoradiotherapy

Secondary Outcome Measure Information:

Title

Time to distant disease

Time Frame

The time to the first diagnosis of lymph node or other distant disease, confirmed via PET/CT, MRI, CT or pathology

Title

Time to maximal tumour response after CRT

Time Frame

The time when tumour regressed to its minimum thickness and when MRI

Title

Time to local re-growth

Time Frame

The time until the first recorded increase in Mandard grade, or tumour thickness or length, on MRI

Title

Percentages of positive margins, and sphincter-preservation rates in patients who have had surgery

Time Frame

At the end of the study - all patients who had surgery for progression of local disease

Title

Progression-free and overall survival

Time Frame

Measured from the end of CRT (cohort A) or end of adjuvant chemotherapy (cohort B). Surviving patients in continued CR will be censored at the date of last follow-up (clinic visit or imaging).

Title

Quality of Life including long-term bowel, urinary and sexual function

Time Frame

10 years after registration, or five years post-surgery.

Title

To correlate the expression of biological markers which may predict for pathological complete response with progression free survival

Time Frame

End of study

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age > 18 years Locally invasive high-risk rectal adenocarcinoma as defined by the presence on MRI of at least one of the following: i) Tumours within 1mm of mesorectal fascia i.e. circumferential resection margin threatened or involved ii)T3 tumours at/below levators iii)Tumours extending ≥5mm into peri-rectal fat iv)T4 tumours (including the involvement of bladder or vagina if surgical resection is possible with clear margins) v)Presence of extra-mural venous invasion (primary tumour is therefore at least T3) vi)T2 N0/1/2 tumours requiring Abdomino-Perineal Excision, within 1mm of mesorectal fascia i.e. circumferential resection margin threatened or involved The absence of malignant pelvic side-wall disease, local recurrence (either after TME or wide local excision) or metastatic disease Completion of pre-operative long-course CRT No viable disease seen at MRI performed 4 weeks after long-course CRT, confirmed at 8 week MRI Evidence of partial response of rectal tumour to pre-operative long-course CRT at 4 week MRI which continues to show an incremental response at 8 week MRI. Histological diagnosis of adenocarcinoma of rectum. WHO performance status 0, 1 or 2. No evidence of metastatic disease as determined by CT scan of chest, abdomen, pelvis or other investigations such as PET scan or biopsy if required. Informed written consent Exclusion Criteria: Age < 18 years. Absence of concomitant chemotherapy. RT dose below 50Gy. Stable disease at 4 week MRI. Disease that demonstrates a partial response at 4 week MRI but shows no evidence of an incremental response at 8 week MRI. Pregnancy or breast feeding Short course pre-operative radiotherapy Previous pelvic radiotherapy Medical or psychiatric conditions that compromise the patient's ability to give informed consent Any contra-indication to MRI scanning, eg Cardiac Pacemaker or Hip prosthesis. Any patients within the EXPERT-C trial. Tumours which are mucinous (>50% mucin seen on MRI), as these are more likely to be PET negative

Facility Information:

Facility Name

Royal Marsden NHS Foundation Trust

City

London

Country

United Kingdom

12. IPD Sharing Statement

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Avoiding Surgery in Rectal Cancer After Pre-Operative Therapy

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