Prediction of Response to Neoadjuvant Therapy in Rectal Cancer (PRENT-LARC)

May 8, 2015 updated by: Medhat Alaker, Colchester General Hospital

Prediction of Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

The purpose of this study is to determine whether 18F-FDG-PET-CT and texture analysis of MRI performed 9 weeks after Neoadjuvant Chemo-radiotherapy in patients with locally advanced rectal cancer has the ability to identify patients with Complete Response.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

In recent years, treatment with NCRT has revolutionised management of LARC. In addition to downstaging the tumour in 62% of cases, half of which decrease by more than 1 T stage; pathological complete response (pCR), with no viable tumour cells left in resected specimens, was demonstrated in up to 30% of patients. Only 3% of patients showed progressive disease. It has recently been shown that those with pathological complete response survive longer than those with partial response, with figures for 5-year disease free survival quoted between 83 and 91% for pCR; versus 65% for non pCR. Furthermore, it has been argued that those tumours which are sensitive to radiotherapy have a favourable biological tumour profile, with fewer propensities to recur or to metastasise than aggressive non-radiosensitive tumours. The key is to accurately be able to identify patients who exhibit complete response to radiotherapy, or to predict those who might show complete response.

Positron Emission Tomography (18-F-FDG-PET-CT) as a tumour biomarker after radiotherapy has been shown to be able to predict patients who have responded to chemo radiotherapy, with a sensitivity of 79% and specificity of 88%. Texture Analysis (TA) assesses the aggressiveness of the tumour by assessing intra-tumoural heterogeneity. It has already been shown to be effective in assessing biological characteristics of solid tumours, including the oesophagus, breast, and liver.

The aim of this study is to utilise these two novel molecular imaging techniques to identify rectal cancer patients who have responded completely from neoadjuvant chemo-radiotherapy. Parameters will be calculated as changes in measurable variables from baseline to post treatment scans.

Pilot data The watch-and-wait approach could potentially reduce treatment-related toxicity in selected rectal cancer patients who have a clinical complete response (cCR) after chemoradiation. The "watch & wait" protocol has been adopted from studies performed in Brazil, United Kingdom, and the Netherlands.

Studies indicate that accurate assessment of response to neoadjuvant therapy is the key to selecting patients who will benefit from the watch & wait approach. Therefore, determining the modality with highest accuracy and cost-effectiveness has been the holy grail of managing locally advanced rectal cancers.

A study performed by our Chief Investigator on the efficiency and accuracy of 18-F-FDG-PET-CT has concluded that PET-CT has a proven role and is cost effective in monitoring therapy and in detecting recurrence in colorectal cancers; as this technology combines picomolar sensitivity with high-resolution CT imaging. It has therefore shown to be more sensitive than plain CT imaging in detecting recurrence and monitoring response to therapy. In other studies, the reported accuracy for PET-CT in determining responsiveness to NCRT was around 80%. Baseline PET-CT and subsequent PET-CT parameters, including SUV-based measurements, have been shown to be highly accurate in determining responses to NCRT.

Texture Analysis is a biomarker technique that measures heterogeneity within solid tumours. Textural parameters (coefficient of variation [COV], skewness, and kurtosis) applied on PET-CT images has been shown to be able to predict response to NCRT, and to predict survival. A pilot study performed at our institution has indeed showed that textural parameters performed on pelvic MRI were associated with improved overall survival and disease- free survival.

Study hypothesis

  • PET-CT restaging done at 9 weeks rather than 6 weeks will be a more accurate predictor in assessing response to NCRT.
  • Texture analysis of rectal MRI scans is a strong biomarker in assessing tumour response and identifying patients with Complete Response.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Colchester, United Kingdom, CO4 5JL
        • Colchester General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with biopsy-proven confirmed rectal cancer
  • MRI stage: T3/T4 and/or N1/N0.
  • No contraindication to MRI and PET-CT.

Exclusion Criteria:

  • Contraindication to MRI and/or PET-CT.
  • Inability to consent.
  • Severe claustrophobia.
  • Distant metastases.
  • Synchronous tumour.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Long Course Radiotherapy
all patients diagnosed with rectal cancer, amenable for neoadjuvant chemoradiotherapy, who agree to participate in this study will undergo 2 PET-CT scans: at baseline and 9 weeks after commencing therapy.
Device: PET-CT Scan
patients will have 2 PET CT scans: one before radiotherapy, and one 9 weeks after.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Accuracy of Texture analysis PET-CT
Time Frame: 6 months
Sensitivity will be calculated from 2x2 contingency table.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between tumour response parameters to survival.
Time Frame: 6 months
Correlation coefficient (r)
6 months
Accuracy of Texture analysis MRI
Time Frame: 6 months
Sensitivity will be calculated from 2x2 contingency table.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Colchester General Hospital

Collaborators

Anglia Ruskin University

Investigators

  • Principal Investigator: Tan Arulampalam, MD, ICENI Centre director

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2015

Primary Completion (Anticipated)

September 1, 2017

Study Completion (Anticipated)

September 1, 2017

Study Registration Dates

First Submitted

April 23, 2015

First Submitted That Met QC Criteria

May 7, 2015

First Posted (Estimate)

May 8, 2015

Study Record Updates

Last Update Posted (Estimate)

May 12, 2015

Last Update Submitted That Met QC Criteria

May 8, 2015

Last Verified

May 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TBA (ethics)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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