AdenocarcinomaMARVELNCT01995942
Molecular, Pathologic and MRI Investigation of the Prognostic and Redictive Importance of Extramural Venous Invasion in Rectal Cancer (MARVEL) Trial
An observational study of Adenocarcinoma and Rectal Diseases, run by Royal Marsden NHS Foundation Trust at 19 sites in United Kingdom.
Trial summary
Extramural venous invasion (EMVI) is the spread of microscopic tumour cells into the veins around the tumour. Rectal cancer treatment has improved greatly over recent years. However, it is important for us to learn as much about the tumours as possible in order to develop newer therapies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenocarcinoma, Rectal Diseases, Colorectal Neoplasms
- How many people
- 246 participants
- Where
- 19 sitesUnited Kingdom
- Study dates
- 7 Jun 2013to 2 Feb 2022
- Phase
- Observational
- 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
Study population: Patients aged over 18 years of age presenting with adenocarcinoma of the rectum. This will be diagnosed on colonoscopy and/or biopsy and MRI, and treatment strategy will include pre-operative CRT followed by surgery.
Who may be able to join
- Locally advanced primary rectal cancer (requiring pre-operative treatment); diagnosed on tissue biopsy
- Adult patients - over 18 years
- Able to undergo curative (TME) surgery
- Able to undergo MRI and CT with relevant contrast agent
- Able to undergo LCRT
Who cannot join
- Metastatic disease at presentation
- Emergency diagnosis/treatment
- Unable to undergo staging (MRI and CT) or treatment procedures (LCRT/surgery)
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
United Kingdom19 sites
Queen's Hospital, Burton Upon Trent
Burton-on-Trent, Staffordshire, Burton-on-Trent
University Hospital Coventry
Coventry, West Midlands, CV2 2DX
Leighton Hospital
Crewe, Cheshire, CW1 4QJ
North Manchester General Hospital
Crumpsall, Manchester, M8 5RB
Royal Surrey County Hospital
Guildford, Surrey, GU2 7XX
Homerton University Hospital
London, Surrey, E9 6SR
Royal Marsden Hospital
London and Surrey
George Eliot Hospital
Nuneaton, CV10 7DJ
Peterborough City Hospital
Peterborough, Cambridgeshire, PE3 9GZ
Derriford Hospital
Plymouth, Devon, PL6 8DH
Poole Hospital
Poole, Dorset, BH15 2JB
Alexandra Hospital
Redditch, B98 7UB
Salisbury District Hospital
Salisbury, Wiltshire, SP2 8BJ
University Hospital Southampton NHS Foundation Trust
Southampton, Hampshire, SO16 6YD
Kings Mill Hospital
Sutton in Ashfield, Nottinghamshire, NG17 4JL
Croydon University Hospital
Thornton Heath, Surrey, CR7 7YE
Royal Cornwall Hospital
Truro, Cornwall, TR1 3LQ
South Warwickshire NHS Foundation Trust (Warwick Hospital)
Warwick, CV34 5BW
University Hospital of South Manchester
Wythenshawe, Manchester, M23 9LT
About this study
Official title: Molecular, Pathologic and MRI Investigation of the Prognostic and Redictive Importance of Extramural Venous Invasion in Rectal Cancer
Extramural venous invasion (EMVI) is the spread of microscopic tumour cells into the veins around the tumour. Rectal cancer treatment has improved greatly over recent years. However, it is important for us to learn as much about the tumours as possible in order to develop newer therapies. Current treatments may benefit from new genetic information relating to the cancer. We hope to identify genetic differences in certain types of rectal cancer which will allow future treatments.
Read the detailed description
Neoadjuvant chemoradiotherapy (CRT) is widely accepted as beneficial to selected patients in terms of decreased risk of local recurrence and overall survival. Current management of rectal cancer involves risk stratification through pre-operative staging leading to formulation of treatment strategy. Very little is known about the long-term outcomes and response to CRT on MRI detected extramural venous invasion (mrEMVI). Although mrEMVI is accepted as a marker of poor prognosis, whether it has a predictive value and should be specifically treated is not known.
Molecular and genetic profiling provides us with an opportunity to understand the underlying mechanisms which govern clinical behaviour in rectal cancer. Using high-throughput technology such as tissue microarray analysis allows large-scale analysis of specimens in a relatively short amount of time. It offers the ability to compare the molecular profiles of different subtypes of rectal cancer such as mrEMVI-positive and -negative tumours and whether any changes are observed following CRT. This can then be correlated with clinical behaviour over the medium and long-term with regards to local recurrence, distant metastases and overall survival.
This study will identify important differences between key rectal cancer tumour subtypes. Identification of reliable pathological markers of EMVI pathways (from both the primary tumour sample, but more importantly from the pre-operative biopsies) has real potential for taking us a step closer to more personalised management of rectal cancer by establishing prognostic biomarkers reflective of disease type, but also through the underlying biology that may be highlighted (with its promise of therapeutic translation).
- Conditions
- Adenocarcinoma, Rectal Diseases, Colorectal Neoplasms, Adenocarcinoma, Mucinous, Carcinoma, Neoplasms, Glandular and Epithelial
- Keywords
- Rectal Cancer, EMVI, Extramural Venous Invasion, Microarray, Biomarker, mrEMVI, Tumour Regression Grade, Cancer, Circumferential Resection Margin, CRM, MRI, Radiology, Surgery, Pathology
- Medical subject headings
- Adenocarcinoma, Rectal Diseases, Colorectal Neoplasms, Adenocarcinoma, Mucinous, Carcinoma, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Patients with mrEMVI positive rectal cancer | |
| Group 2 | Patients with mrEMVI negative rectal cancer |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint will be time to relapse pertaining to the primary objective of relapse rate at 1 year and 3 years.
Measured: 3 years
Secondary outcomes (2)
Response rates (in terms of mrTstage, mrN stage, involvement of CRM (circumferential resection margin) and mrTRG (tumour regression grade)) in addition to recurrence rates at 1 year and 3 years.
Measured: 3 years
Measurement of the change in mrEMVI from pre to post pre-operative therapy, will be based on a new proposed EMVI-TRG classification (EMVI TRG 1-5).
mrEMVI Regression Grade Scoring Table: Grade 5 - No response (intermediate signal intensity, same appearances as original tumour) Grade 4 - Slight response (little areas of fibrosis or mucin but mostly tumour) Grade 3 - Moderate response (>50% fibrosis or mucin, and visible intermediate signal) Grade 2 - Good response (dense fibrosis; no obvious residual tumour, signifying minimal residual disease or no tumour) Grade 1 - Radiological complete response (rCR) (linear/crescentic 1-2mm scar in mucosa or submucosa only.)
Measured: 5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2013 (estimated)
- Study start7 Jun 2013
- Primary completion2 Feb 2017
- Study completion2 Feb 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 246 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royal Marsden NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Pelican Cancer Foundation
- Responsible party
- Sponsor
- Investigators
- Gina Brown, Principal investigator, Royal Marsden NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01995942
- Sponsor's protocol ID
- CCR3873
- Acronym
- MARVEL
- Status last verified
- Sep 2018
- First submitted
- 21 Nov 2013
- Last updated
- 14 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular, Pathologic and MRI Investigation of the Prognostic and Redictive Importance of Extramural Venous Invasion in Rectal Cancer
- ClinicalTrials.gov ID
- NCT01995942
- Acronym / sponsor ID
- MARVEL / CCR3873
- Conditions
- Adenocarcinoma, Rectal Diseases, Colorectal Neoplasms, Adenocarcinoma, Mucinous, Carcinoma, Neoplasms, Glandular and Epithelial
- Keywords
- Rectal Cancer, EMVI, Extramural Venous Invasion, Microarray, Biomarker, mrEMVI, Tumour Regression Grade, Cancer
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 246 participants (actual)
- Lead sponsor
- Royal Marsden NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Pelican Cancer Foundation
- Study start
- 7 Jun 2013 (actual)
- Primary completion
- 2 Feb 2017 (actual)
- Study completion
- 2 Feb 2022 (estimated)
- First posted
- 27 Nov 2013 (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.
Extramural venous invasion (EMVI) is the spread of microscopic tumour cells into the veins around the tumour. Rectal cancer treatment has improved greatly over recent years. However, it is important for us to learn as much about the tumours as possible in order to develop newer therapies. Current treatments may benefit from new genetic information relating to the cancer. We hope to identify genetic differences in certain types of rectal cancer which will allow future treatments.
Detailed description
Neoadjuvant chemoradiotherapy (CRT) is widely accepted as beneficial to selected patients in terms of decreased risk of local recurrence and overall survival. Current management of rectal cancer involves risk stratification through pre-operative staging leading to formulation of treatment strategy. Very little is known about the long-term outcomes and response to CRT on MRI detected extramural venous invasion (mrEMVI). Although mrEMVI is accepted as a marker of poor prognosis, whether it has a predictive value and should be specifically treated is not known.
Molecular and genetic profiling provides us with an opportunity to understand the underlying mechanisms which govern clinical behaviour in rectal cancer. Using high-throughput technology such as tissue microarray analysis allows large-scale analysis of specimens in a relatively short amount of time. It offers the ability to compare the molecular profiles of different subtypes of rectal cancer such as mrEMVI-positive and -negative tumours and whether any changes are observed following CRT. This can then be correlated with clinical behaviour over the medium and long-term with regards to local recurrence, distant metastases and overall survival.
This study will identify important differences between key rectal cancer tumour subtypes. Identification of reliable pathological markers of EMVI pathways (from both the primary tumour sample, but more importantly from the pre-operative biopsies) has real potential for taking us a step closer to more personalised management of rectal cancer by establishing prognostic biomarkers reflective of disease type, but also through the underlying biology that may be highlighted (with its promise of therapeutic translation).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | – | –Patients with mrEMVI positive rectal cancer |
| Group 2 | – | –Patients with mrEMVI negative rectal cancer |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients aged over 18 years of age presenting with adenocarcinoma of the rectum. This will be diagnosed on colonoscopy and/or biopsy and MRI, and treatment strategy will include pre-operative CRT followed by surgery.
Key inclusion criteria (5 listed)
- Locally advanced primary rectal cancer (requiring pre-operative treatment); diagnosed on tissue biopsy
- Adult patients - over 18 years
- Able to undergo curative (TME) surgery
- Able to undergo MRI and CT with relevant contrast agent
- Able to undergo LCRT
Key exclusion criteria (3 listed)
- Metastatic disease at presentation
- Emergency diagnosis/treatment
- Unable to undergo staging (MRI and CT) or treatment procedures (LCRT/surgery)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
The primary endpoint will be time to relapse pertaining to the primary objective of relapse rate at 1 year and 3 years.
Time frame: 3 years
2 secondary outcomes
Response rates (in terms of mrTstage, mrN stage, involvement of CRM (circumferential resection margin) and mrTRG (tumour regression grade)) in addition to recurrence rates at 1 year and 3 years.
Time frame: 3 years
Measurement of the change in mrEMVI from pre to post pre-operative therapy, will be based on a new proposed EMVI-TRG classification (EMVI TRG 1-5).
Time frame: 5 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2018.
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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.
Gina Brown principal investigator
Royal Marsden NHS Foundation Trust
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Adenocarcinoma and Rectal Diseases, run by Royal Marsden NHS Foundation Trust at 19 sites 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 5 inclusion and 3 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 14 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites 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.
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?
The primary endpoint will be time to relapse pertaining to the primary objective of relapse rate at 1 year and 3 years. (time frame: 3 years). 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 14 Sep 2018.