Avoiding Surgery in Rectal Cancer After Pre-Operative Therapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01047969
Recruitment Status : Active, not recruiting
First Posted : January 13, 2010
Last Update Posted : May 30, 2016
Information provided by (Responsible Party):
Ann Gandolfi, Royal Marsden NHS Foundation Trust

Brief Summary:
An assessment of the safety of omission of surgery following a complete response to chemotherapy and radiotherapy, or radiotherapy alone, for rectal cancer.

Condition or disease Intervention/treatment Phase
Rectal Adenocarcinoma Drug: Adjuvant Chemotherapy Procedure: Surgery Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 99 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Non-Operative Treatment for Rectal Cancer Following Complete Response to Neo-Adjuvant Therapy
Study Start Date : September 2006
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2019

Intervention Details:
  • Drug: Adjuvant Chemotherapy
    If after MRI + FDG-PET 8 weeks post CRT the patient shows no visible tumour or further regression adjuvant chemotherapy will be considered.
  • Procedure: Surgery
    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 Measures :
  1. 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) [ Time Frame: Two years post end of chemoradiotherapy ]
  2. 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. [ Time Frame: Two years post end of chemoradiotherapy ]

Secondary Outcome Measures :
  1. 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 ]
  2. Time to maximal tumour response after CRT [ Time Frame: The time when tumour regressed to its minimum thickness and when MRI ]
  3. Time to local re-growth [ Time Frame: The time until the first recorded increase in Mandard grade, or tumour thickness or length, on MRI ]
  4. 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 ]
  5. 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). ]
  6. Quality of Life including long-term bowel, urinary and sexual function [ Time Frame: 10 years after registration, or five years post-surgery. ]
  7. To correlate the expression of biological markers which may predict for pathological complete response with progression free survival [ Time Frame: End of study ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

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 identifier (NCT number): NCT01047969

United Kingdom
Royal Marsden NHS Foundation Trust
London, United Kingdom
Sponsors and Collaborators
Royal Marsden NHS Foundation Trust

Responsible Party: Ann Gandolfi, Julie Curtis, Royal Marsden NHS Foundation Trust Identifier: NCT01047969     History of Changes
Other Study ID Numbers: 2759
First Posted: January 13, 2010    Key Record Dates
Last Update Posted: May 30, 2016
Last Verified: May 2016

Keywords provided by Ann Gandolfi, Royal Marsden NHS Foundation Trust:
locally invasive high-risk rectal adenocarcinoma

Additional relevant MeSH terms:
Rectal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases