Rectal NeoplasmsPRENT-LARCNCT02439086
Prediction of Response to Neoadjuvant Therapy in Rectal Cancer
A study testing PET-CT Scan in people with Rectal Neoplasms, run by Colchester General Hospital at 1 site in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Rectal Neoplasms
- What is being tested?
- PET-CT Scan
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Sep 2015to Sep 2017
- Phase
- Interventional
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with biopsy-proven confirmed rectal cancer
- MRI stage: T3/T4 and/or N1/N0.
- No contraindication to MRI and PET-CT.
Who cannot join
- Contraindication to MRI and/or PET-CT.
- Inability to consent.
- Severe claustrophobia.
- Distant metastases.
- Synchronous tumour.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Rectal Neoplasms
- Being tested
- PET-CT Scan
- Keywords
- rectal cancer, neoadjuvant chemoradiotherapy, long course radiotherapy, response
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PET-CT ScanDevice
patients will have 2 PET CT scans: one before radiotherapy, and one 9 weeks after.
| Study group | Role | What they receive |
|---|---|---|
| Long Course Radiotherapy | Experimental | 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. Receives: Device: PET-CT Scan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Accuracy of Texture analysis PET-CT
Sensitivity will be calculated from 2x2 contingency table.
Measured: 6 months
Secondary outcomes (2)
Correlation between tumour response parameters to survival.
Correlation coefficient (r)
Measured: 6 months
Accuracy of Texture analysis MRI
Sensitivity will be calculated from 2x2 contingency table.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2015 (estimated)
- Study startSep 2015
- Primary completionSep 2017 (estimated)
- Study completionSep 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Rectal NeoplasmsStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Colchester General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Anglia Ruskin University
- Responsible party
- Principal investigator, Medhat Alaker, Colchester General Hospital
- Investigators
- Tan Arulampalam, MD, Principal investigator, ICENI Centre director
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02439086
- Sponsor's protocol ID
- TBA (ethics)
- Acronym
- PRENT-LARC
- Status last verified
- May 2015
- First submitted
- 23 Apr 2015
- Last updated
- 12 May 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Arulampalam TH, Costa DC, Loizidou M, Visvikis D, Ell PJ, Taylor I. Positron emission tomography and colorectal cancer. Br J Surg. 2001 Feb;88(2):176-89. doi: 10.1046/j.1365-2168.2001.01657.x.
PubMed 11167864Bundschuh RA, Dinges J, Neumann L, Seyfried M, Zsoter N, Papp L, Rosenberg R, Becker K, Astner ST, Henninger M, Herrmann K, Ziegler SI, Schwaiger M, Essler M. Textural Parameters of Tumor Heterogeneity in (1)(8)F-FDG PET/CT for Therapy Response Assessment and Prognosis in Patients with Locally Advanced Rectal Cancer. J Nucl Med. 2014 Jun;55(6):891-7. doi: 10.2967/jnumed.113.127340. Epub 2014 Apr 21.
PubMed 24752672HABR-GAMA, A., PEREZ, R., LYNN, P., SãO JULIãO, G. and GAMA RODRIGUES, J., 2012. Selective non-operative management of distal rectal cancer: The Watch & Wait Protocol. In: R. SCHIESSEL and P. METZGER, eds, Springer Vienna, pp. 43-53.
Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U Jr, Silva e Sousa AH Jr, Campos FG, Kiss DR, Gama-Rodrigues J. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg. 2004 Oct;240(4):711-7; discussion 717-8. doi: 10.1097/01.sla.0000141194.27992.32.
PubMed 15383798Maas M, Nelemans PJ, Valentini V, Das P, Rodel C, Kuo LJ, Calvo FA, Garcia-Aguilar J, Glynne-Jones R, Haustermans K, Mohiuddin M, Pucciarelli S, Small W Jr, Suarez J, Theodoropoulos G, Biondo S, Beets-Tan RG, Beets GL. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010 Sep;11(9):835-44. doi: 10.1016/S1470-2045(10)70172-8. Epub 2010 Aug 6.
PubMed 20692872Niccoli-Asabella A, Altini C, De Luca R, Fanelli M, Rubini D, Caliandro C, Montemurro S, Rubini G. Prospective analysis of 18F-FDG PET/CT predictive value in patients with low rectal cancer treated with neoadjuvant chemoradiotherapy and conservative surgery. Biomed Res Int. 2014;2014:952843. doi: 10.1155/2014/952843. Epub 2014 May 4.
PubMed 24877151Aker M, Ganeshan B, Afaq A, Wan S, Groves AM, Arulampalam T. Magnetic Resonance Texture Analysis in Identifying Complete Pathological Response to Neoadjuvant Treatment in Locally Advanced Rectal Cancer. Dis Colon Rectum. 2019 Feb;62(2):163-170. doi: 10.1097/DCR.0000000000001224.
PubMed 30451764
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prediction of Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.
- ClinicalTrials.gov ID
- NCT02439086
- Acronym / sponsor ID
- PRENT-LARC / TBA (ethics)
- Conditions
- Rectal Neoplasms
- Keywords
- rectal cancer, neoadjuvant chemoradiotherapy, long course radiotherapy, response
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Colchester General HospitalUniversity, hospital or other
- Collaborators
- Anglia Ruskin University
- Study start
- Sep 2015
- Primary completion
- Sep 2017 (estimated)
- Study completion
- Sep 2017 (estimated)
- First posted
- 8 May 2015 (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 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.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Long Course Radiotherapy | Experimental | Device: PET-CT Scanall 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Patients with biopsy-proven confirmed rectal cancer
- MRI stage: T3/T4 and/or N1/N0.
- No contraindication to MRI and PET-CT.
Key exclusion criteria (5 listed)
- Contraindication to MRI and/or PET-CT.
- Inability to consent.
- Severe claustrophobia.
- Distant metastases.
- Synchronous tumour.
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 |
|---|---|---|
| PET-CT Scanpatients will have 2 PET CT scans: one before radiotherapy, and one 9 weeks after. | Device | Long Course Radiotherapy |
Primary outcome
Accuracy of Texture analysis PET-CT
Time frame: 6 months
Sensitivity will be calculated from 2x2 contingency table.
2 secondary outcomes
Correlation between tumour response parameters to survival.
Time frame: 6 months
Accuracy of Texture analysis MRI
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2015.
- Background: PubMed 11167864Arulampalam TH, Costa DC, Loizidou M, Visvikis D, Ell PJ, Taylor I. Positron emission tomography and colorectal cancer. Br J Surg. 2001 Feb;88(2):176-89. doi: 10.1046/j.1365-2168.2001.01657.x.
- Background: PubMed 24752672Bundschuh RA, Dinges J, Neumann L, Seyfried M, Zsoter N, Papp L, Rosenberg R, Becker K, Astner ST, Henninger M, Herrmann K, Ziegler SI, Schwaiger M, Essler M. Textural Parameters of Tumor Heterogeneity in (1)(8)F-FDG PET/CT for Therapy Response Assessment and Prognosis in Patients with Locally Advanced Rectal Cancer. J Nucl Med. 2014 Jun;55(6):891-7. doi: 10.2967/jnumed.113.127340. Epub 2014 Apr 21.
- BackgroundHABR-GAMA, A., PEREZ, R., LYNN, P., SãO JULIãO, G. and GAMA RODRIGUES, J., 2012. Selective non-operative management of distal rectal cancer: The Watch & Wait Protocol. In: R. SCHIESSEL and P. METZGER, eds, Springer Vienna, pp. 43-53.
- Background: PubMed 15383798Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U Jr, Silva e Sousa AH Jr, Campos FG, Kiss DR, Gama-Rodrigues J. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg. 2004 Oct;240(4):711-7; discussion 717-8. doi: 10.1097/01.sla.0000141194.27992.32.
- Background: PubMed 20692872Maas M, Nelemans PJ, Valentini V, Das P, Rodel C, Kuo LJ, Calvo FA, Garcia-Aguilar J, Glynne-Jones R, Haustermans K, Mohiuddin M, Pucciarelli S, Small W Jr, Suarez J, Theodoropoulos G, Biondo S, Beets-Tan RG, Beets GL. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010 Sep;11(9):835-44. doi: 10.1016/S1470-2045(10)70172-8. Epub 2010 Aug 6.
- Background: PubMed 24877151Niccoli-Asabella A, Altini C, De Luca R, Fanelli M, Rubini D, Caliandro C, Montemurro S, Rubini G. Prospective analysis of 18F-FDG PET/CT predictive value in patients with low rectal cancer treated with neoadjuvant chemoradiotherapy and conservative surgery. Biomed Res Int. 2014;2014:952843. doi: 10.1155/2014/952843. Epub 2014 May 4.
- Derived from this study: PubMed 30451764Aker M, Ganeshan B, Afaq A, Wan S, Groves AM, Arulampalam T. Magnetic Resonance Texture Analysis in Identifying Complete Pathological Response to Neoadjuvant Treatment in Locally Advanced Rectal Cancer. Dis Colon Rectum. 2019 Feb;62(2):163-170. doi: 10.1097/DCR.0000000000001224.
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Neoplasms
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.
Tan Arulampalam, MD principal investigator
ICENI Centre director
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PET-CT Scan in people with Rectal Neoplasms, run by Colchester General Hospital 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 3 inclusion and 5 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 12 May 2015. 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.
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?
Contact Medhat S Alaker, MCh, MD(Res) (+447746147851, medhat.alaker@nhs.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Accuracy of Texture analysis PET-CT (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02439086, which also lists 7 linked publications.
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 12 May 2015.