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Molecular, Pathologic and MRI Investigation of the Prognostic and Redictive Importance of Extramural Venous Invasion in Rectal Cancer (MARVEL) Trial (MARVEL)

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ClinicalTrials.gov Identifier: NCT01995942
Recruitment Status : Active, not recruiting
First Posted : November 27, 2013
Last Update Posted : September 14, 2018
Sponsor:
Collaborator:
Pelican Cancer Foundation
Information provided by (Responsible Party):
Royal Marsden NHS Foundation Trust

Tracking Information
First Submitted Date November 21, 2013
First Posted Date November 27, 2013
Last Update Posted Date September 14, 2018
Actual Study Start Date June 7, 2013
Actual Primary Completion Date February 2, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: November 26, 2013)
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 ]
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: November 26, 2013)
  • 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 ]
    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.)
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Molecular, Pathologic and MRI Investigation of the Prognostic and Redictive Importance of Extramural Venous Invasion in Rectal Cancer (MARVEL) Trial
Official Title Molecular, Pathologic and MRI Investigation of the Prognostic and Redictive Importance of Extramural Venous Invasion in Rectal Cancer
Brief 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. 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 Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Histopathology samples taken after rectal tumour removal surgery will be analysed using micrarray techniques. The pathological tissue microarrays (TMAs) will be generated using the Alphelys Tissue Arrayer Minicore®3 system. Markers that will be evaluated will be initially directed at epithelial to mesenchymal (EMT) transition pathways, as our preliminary studies suggest that this phylogenetically conserved molecular program has important roles in tumour dissemination and resistance to conventional chemotherapy.
Sampling Method Non-Probability Sample
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.
Condition
  • Adenocarcinoma
  • Rectal Diseases
  • Colorectal Neoplasms
  • Adenocarcinoma, Mucinous
  • Carcinoma
  • Neoplasms, Glandular and Epithelial
  • Neoplasms by Histologic Type
  • Neoplasms
  • Neoplasms, Cystic, Mucinous, and Serous
  • Intestinal Neoplasms
  • Gastrointestinal Neoplasms
  • Digestive System Neoplasms
  • Neoplasms by Site
  • Digestive System Diseases
  • Gastrointestinal Diseases
  • Intestinal Diseases
Intervention Not Provided
Study Groups/Cohorts
  • Group 1
    Patients with mrEMVI positive rectal cancer
  • Group 2
    Patients with mrEMVI negative rectal cancer
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Active, not recruiting
Actual Enrollment
 (submitted: February 28, 2017)
246
Original Estimated Enrollment
 (submitted: November 26, 2013)
160
Estimated Study Completion Date February 2, 2022
Actual Primary Completion Date February 2, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  1. Locally advanced primary rectal cancer (requiring pre-operative treatment); diagnosed on tissue biopsy
  2. Adult patients - over 18 years
  3. Able to undergo curative (TME) surgery
  4. Able to undergo MRI and CT with relevant contrast agent
  5. Able to undergo LCRT

Exclusion Criteria

  1. Metastatic disease at presentation
  2. Emergency diagnosis/treatment
  3. Unable to undergo staging (MRI and CT) or treatment procedures (LCRT/surgery)
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number NCT01995942
Other Study ID Numbers CCR3873
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Royal Marsden NHS Foundation Trust
Study Sponsor Royal Marsden NHS Foundation Trust
Collaborators Pelican Cancer Foundation
Investigators
Principal Investigator: Gina Brown Royal Marsden NHS Foundation Trust
PRS Account Royal Marsden NHS Foundation Trust
Verification Date September 2018