Rectal AdenocarcinomaPhase 2NCT01047969
Avoiding Surgery in Rectal Cancer After Pre-Operative Therapy
A Phase 2 study testing Adjuvant Chemotherapy and Surgery in people with Rectal Adenocarcinoma, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Adenocarcinoma
- What is being tested?
- Adjuvant Chemotherapy and Surgery
- Type of treatment
- Surgery or procedure
- How many people
- 99 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 6 Jun 2006to Jun 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Non-Operative Treatment for Rectal Cancer Following Complete Response to Neo-Adjuvant Therapy
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.
Read the 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.
- Conditions
- Rectal Adenocarcinoma
- Being tested
- Adjuvant Chemotherapy, Surgery
- Keywords
- locally invasive high-risk rectal adenocarcinoma
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adjuvant ChemotherapyDrug
If after MRI + FDG-PET 8 weeks post CRT the patient shows no visible tumour or further regression adjuvant chemotherapy will be considered.
SurgeryProcedure or 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.
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Two years post end of chemoradiotherapy
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.
Measured: Two years post end of chemoradiotherapy
Secondary outcomes (7)
Time to distant disease
Measured: The time to the first diagnosis of lymph node or other distant disease, confirmed via PET/CT, MRI, CT or pathology
Time to maximal tumour response after CRT
Measured: The time when tumour regressed to its minimum thickness and when MRI
Time to local re-growth
Measured: The time until the first recorded increase in Mandard grade, or tumour thickness or length, on MRI
Percentages of positive margins, and sphincter-preservation rates in patients who have had surgery
Measured: At the end of the study - all patients who had surgery for progression of local disease
Progression-free and overall survival
Measured: 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).
Quality of Life including long-term bowel, urinary and sexual function
Measured: 10 years after registration, or five years post-surgery.
To correlate the expression of biological markers which may predict for pathological complete response with progression free survival
Measured: End of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2010 (estimated)
- Study start6 Jun 2006
- Primary completionJun 2019 (estimated)
- Study completionJun 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rectal AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by Royal Marsden NHS Foundation TrustThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 99 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royal Marsden NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ann Gandolfi, Royal Marsden NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01047969
- Sponsor's protocol ID
- 2759
- Status last verified
- May 2016
- First submitted
- 12 Jan 2010
- Last updated
- 13 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-Operative Treatment for Rectal Cancer Following Complete Response to Neo-Adjuvant Therapy
- ClinicalTrials.gov ID
- NCT01047969
- Acronym / sponsor ID
- 2759
- Conditions
- Rectal Adenocarcinoma
- Keywords
- locally invasive high-risk rectal adenocarcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 99 participants (actual)
- Lead sponsor
- Royal Marsden NHS Foundation TrustUniversity, hospital or other
- Study start
- 6 Jun 2006 (actual)
- Primary completion
- Jun 2019 (estimated)
- Study completion
- Jun 2019 (estimated)
- First posted
- 13 Jan 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Adjuvant ChemotherapyIf after MRI + FDG-PET 8 weeks post CRT the patient shows no visible tumour or further regression adjuvant chemotherapy will be considered. | Drug | – |
| SurgeryIf after MRI + FDG-PET 8 weeks post CRF no further regression or growth of disease occurs the patient will be referred for surgery. | Procedure or surgery | – |
Primary outcome
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
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
7 secondary outcomes
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
Time to maximal tumour response after CRT
Time frame: The time when tumour regressed to its minimum thickness and when MRI
Time to local re-growth
Time frame: The time until the first recorded increase in Mandard grade, or tumour thickness or length, on MRI
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
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).
Quality of Life including long-term bowel, urinary and sexual function
Time frame: 10 years after registration, or five years post-surgery.
To correlate the expression of biological markers which may predict for pathological complete response with progression free survival
Time frame: End of study
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Adjuvant Chemotherapy and Surgery in people with Rectal Adenocarcinoma, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jun 2019; AzTrials last refreshed its copy on 2 Nov 2026.