Rectal CancerTRaMANCT01887509
Evaluation of Rectal Tumor Margin Using Confocal Endomicroscopy and Comparison to Histopathology
A study testing Probe-based confocal laser endomicroscopy, Rectoscopy and EUS in people with Rectal Cancer and Rectal Adenocarcinoma, run by IHU Strasbourg at 1 site in France.
Trial summary
This innovative study will involve the use of probe-based confocal laser endomicroscopy, a new medical imaging technology never used for surgical indications to date. Virtual biopsies (pCLE images) will be compared to histopathology analysis. This study focuses on the evaluation of rectal tumor margins. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Cancer, Rectal Adenocarcinoma
- What is being tested?
- Probe-based confocal laser endomicroscopy, Rectoscopy and EUS
- Type of treatment
- Injection or infusion, Medical device, Surgery or procedure
- How many people
- 21 participants
- Where
- 1 siteFrance
- Study dates
- 7 Nov 2013to 17 Oct 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient, male or female over 18 years old
- Patient with rectal adenocarcinoma :
- stage T1 or T2, N0 (one single evaluation, during resection)
- stage N+ or T3 (pre- and post-radiochemotherapy evaluations)
- Absence of contra-indication to rectoscopy conduct
- Patient able to understand the study and to provide written informed consent
Show all 17Show fewer
- Patient registered with the French social security regime
- Non-inclusion criteria:
- Absence of written informed consent
- Patient with known or suspected allergy to fluorescein
- Patient with history of reaction jeopardizing the vital prognosis during angiography
- Patient with history of multiple or serious allergic reaction to drugs
- Patient presenting, in the investigator's judgment, a condition or disease preventing their participation to study procedures
- Patient pregnant or breast-feeding
- Patient within exclusion period from other clinical trial
- Patient having forfeited their freedom of an administrative or legal obligation
- Patient being under guardianship
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
France1 site
Service de chirurgie digestive et endocrinienne - Nouvel Hôpital Civil
Strasbourg, 67000
About this study
This innovative study will involve the use of probe-based confocal laser endomicroscopy, a new medical imaging technology never used for surgical indications to date. Virtual biopsies (pCLE images) will be compared to histopathology analysis.
This study focuses on the evaluation of rectal tumor margins. The hypothesis is that pCLE will allow identification of rectal tumor margin, comparable to that of histopathology. In the future, decision of resection margin could rely on intraoperative pCLE exam.
The proposed study is a feasibility study, first in the indication of rectal cancer.
Read the detailed description
Defining the limits of resection of rectal tumors is often imprecise. The identification of the banks of a tumor becomes critical when it comes to the decision to potentially sacrifice the sphincter during the surgical resection. Currently tumor margins are identified by direct examination by the surgeon, or using flexible endoscopy. Endoscopy and confocal microscopy could provide precise images of tumor enabling the reliable definition of resection margins.
There would be a direct benefit for the patient, whom sphincter could be preserved. pCLE (probe-based Confocal Laser Endomicroscopy) has already been widely used for colorectal lesions, and its value proposition has been demonstrated and validated in several studies. This study is the first using pCLE intraoperatively. Study results may lead the use of pCLE to validate surgical procedure decision (resection margin) and to a revision of patient management for colorectal cancer, by adapting neoadjuvant radiochemotherapy to the patient's responder status.
The goal is to identify tumor margin (lower pole) to optimize the resection margin, and to limit resection of healthy rectal tissue for optimal anal sphincter preservation. Moreover, determining the optimal date of surgery following neoadjuvant radiochemotherapy in rectal cancer is being discussed and no consensus has been reached. Therefore, to date, there is no formal evaluation of tumor response. This is partly due to the lack of information on tumor state and tumor evolution over time, between the end of radiochemotherapy and surgery. Histological follow up of tumor would provide supporting information to fill this gap. However, frequent tumor biopsies are not possible. Alternatively, probe-based confocal laser endomicroscopy (pCLE) could allow for a sequential analysis of tumor response. Response to treatment could be assessed and used to define optimal date of surgical resection, depending on patient responding status to treatment. Responding patients would undergo surgery at a later date than non-responders, in whom surgery could be performed earlier.
Benefits of the study lay in the more accurate definition of resection margins, with its associated potential therapeutic impact of the anal sphincter preservation and in the definition of the optimal date of rectal tumor resection, based on response status to radiochemotherapy.
Study interests are :
- Microscopic structure of tumor will be analyzed at the cellular and microvascular levels and compared to healthy mucosa.
- Evolution of response during and following radiochemotherapy will be assessed, and will help classify patients as responders/non responders.
- pCLE results will be compared to histopathology results on pre-treatment and resection biopsies.
- Images gathered through the imaging modalities (WLE, pCLE, EUS) along with histopathology results will be combined to create an atlas and database of rectal tumors.
- Conditions
- Rectal Cancer, Rectal Adenocarcinoma
- Being tested
- Probe-based confocal laser endomicroscopy, Rectoscopy, EUS, Biopsy and resection
- Keywords
- Rectal cancer, Tumor margin, Confocal endomicroscopy, Virtual biopsy, Fluorescein
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Probe-based confocal laser endomicroscopyDevice
Also called Cellvizio® with ColoFlex probe
Patients will undergo:
- Conventional rectoscopy
- pCLE exam following injection of fluorescein, fluorescent contrast agent
- EUS : echoendoscopy
- Biopsies for histopathology : location identical to those of pCLE
- Tumor resection will be performed according to standard oncologic principles.
All visible lesions will be documented. Both healthy and tumor tissue will be examined. Location of sites of interest will be documented on a schema, completed with photographs of endoscopic view.
Biopsies will be harvested in both healthy and tumor tissue as well.
After all procedures are complete, a second assessment of pCLE images by a third party will be performed.
RectoscopyProcedure or surgery
Patients will undergo:
- Conventional rectoscopy
- pCLE exam following injection of fluorescein, fluorescent contrast agent
- EUS : echoendoscopy
- Biopsies for histopathology : location identical to those of pCLE - Tumor resection will be performed according to standard oncologic principles.
All visible lesions will be documented. Both healthy and tumor tissue will be examined. Location of sites of interest will be documented on a schema, completed with photographs of endoscopic view.
Both healthy and tumor tissue will be examined.
EUSProcedure or surgery
Also called Echoendoscopy
Patients will undergo:
- Conventional rectoscopy
- pCLE exam following injection of fluorescein, fluorescent contrast agent
- EUS : echoendoscopy
- Biopsies for histopathology : location identical to those of pCLE - Tumor resection will be performed according to standard oncologic principles.
All visible lesions will be documented. Both healthy and tumor tissue will be examined. Location of sites of interest will be documented on a schema, completed with photographs of endoscopic view.
Biopsy and resectionProcedure or surgery
Patients will undergo:
- Conventional rectoscopy
- pCLE exam following injection of fluorescein, fluorescent contrast agent
- EUS : echoendoscopy
- Biopsies for histopathology : location identical to those of pCLE
- Tumor resection will be performed according to standard oncologic principles.
All visible lesions will be documented. Both healthy and tumor tissue will be examined. Location of sites of interest will be documented on a schema, completed with photographs of endoscopic view.
Biopsies will be harvested in both healthy and tumor tissue as well.
What is being measured
The primary outcome is the main question the study is designed to answer.
Concordance in identification of lower pole of tumor
Identification of lower pole of tumor will be compared between pCLE (optical images, virtual biopsies) and conventional histopathology (biopsies, postoperative analysis of resected piece). Samples of tumor tissue and closest tissue thought to be disease-free.
Conventional biopsies and virtual biopsies prior to radiochemotherapy start (if applicable) and during surgery.
Measured: Up to 9 months
Secondary outcomes (5)
Identification of tissue characteristics
Microvascularisation density, general microstructure, image interpretation criteria, true/false positive/negative.
Will be assessed for all patients at the time of surgical procedure. Also prior to treatment for patients undergoing radiochemotherapy.
Measured: Up to 9 months
Concordance of techniques (pCLE and histopathology)
Evaluation of concordance between pCLE and conventional histopathology for :
- tissue characterization prior to and after radiochemotherapy, if applicable
- radiochemotherapy response assessment
- resection margin evaluation
For patients undergoing radiochemotherapy, 2 exams: prior to treatment start and during surgery For patients with surgery only, 1 exam: during surgery
Measured: Up to 9 months
Comparison of pCLE results to EUS (echoendoscopy) results
pCLE results will be compared to EUS prior to radiochemotherapy and at the time of resection.
Measured: Upon surgery
Creation of an image bank
Creation of an image bank : identification of quality and safety criteria to be of interest for use at the time of resection
Measured: Up to 9 months
Assessment of predictive value of interpretation criteria
Results will be analyzed to assess whether pCLE interpretation criteria have a predictive value for identification of responder/non-responders patients to radiochemotherapy.
Measured: Up to 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2013 (estimated)
- Study start7 Nov 2013
- Primary completion17 Oct 2017
- Study completion17 Oct 2017
Why it stopped: Difficulties with patients recruitment, study acceptance and protocol implementation.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rectal CancerStudies 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
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- IHU Strasbourg
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joël Leroy, Pr, Principal investigator, Service de Chirurgie Disgestive et Endocrinienne - Nouvel Hôpital Civil - Strasbourg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01887509
- Sponsor's protocol ID
- 12-005
- Other IDs
- 2013-A00406-39
- Acronym
- TRaMA
- Status last verified
- May 2018
- First submitted
- 20 Jun 2013
- Last updated
- 15 May 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Wijsmuller AR, Ghnassia JP, Varatharajah S, Schaeffer M, Leroy J, Marescaux J, Ignat M, Mutter D. Prospective Trial on Probe-Based Confocal Laser Endomicroscopy for the Identification of the Distal Limit in Rectal Adenocarcinoma. Surg Innov. 2018 Aug;25(4):313-322. doi: 10.1177/1553350618773011. Epub 2018 May 7.
PubMed 29732957
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Rectal Tumor Margin Using Confocal Endomicroscopy and Comparison to Histopathology
- ClinicalTrials.gov ID
- NCT01887509
- Acronym / sponsor ID
- TRaMA / 12-005
- Conditions
- Rectal Cancer, Rectal Adenocarcinoma
- Keywords
- Rectal cancer, Tumor margin, Confocal endomicroscopy, Virtual biopsy, Fluorescein
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulties with patients recruitment, study acceptance and protocol implementation.
- Enrolment
- 21 participants (actual)
- Lead sponsor
- IHU StrasbourgUniversity, hospital or other
- Study start
- 7 Nov 2013 (actual)
- Primary completion
- 17 Oct 2017 (actual)
- Study completion
- 17 Oct 2017 (actual)
- First posted
- 27 Jun 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.
This innovative study will involve the use of probe-based confocal laser endomicroscopy, a new medical imaging technology never used for surgical indications to date. Virtual biopsies (pCLE images) will be compared to histopathology analysis.
This study focuses on the evaluation of rectal tumor margins. The hypothesis is that pCLE will allow identification of rectal tumor margin, comparable to that of histopathology. In the future, decision of resection margin could rely on intraoperative pCLE exam.
The proposed study is a feasibility study, first in the indication of rectal cancer.
Detailed description
Defining the limits of resection of rectal tumors is often imprecise. The identification of the banks of a tumor becomes critical when it comes to the decision to potentially sacrifice the sphincter during the surgical resection. Currently tumor margins are identified by direct examination by the surgeon, or using flexible endoscopy. Endoscopy and confocal microscopy could provide precise images of tumor enabling the reliable definition of resection margins.
There would be a direct benefit for the patient, whom sphincter could be preserved. pCLE (probe-based Confocal Laser Endomicroscopy) has already been widely used for colorectal lesions, and its value proposition has been demonstrated and validated in several studies. This study is the first using pCLE intraoperatively. Study results may lead the use of pCLE to validate surgical procedure decision (resection margin) and to a revision of patient management for colorectal cancer, by adapting neoadjuvant radiochemotherapy to the patient's responder status.
The goal is to identify tumor margin (lower pole) to optimize the resection margin, and to limit resection of healthy rectal tissue for optimal anal sphincter preservation. Moreover, determining the optimal date of surgery following neoadjuvant radiochemotherapy in rectal cancer is being discussed and no consensus has been reached. Therefore, to date, there is no formal evaluation of tumor response. This is partly due to the lack of information on tumor state and tumor evolution over time, between the end of radiochemotherapy and surgery. Histological follow up of tumor would provide supporting information to fill this gap. However, frequent tumor biopsies are not possible. Alternatively, probe-based confocal laser endomicroscopy (pCLE) could allow for a sequential analysis of tumor response. Response to treatment could be assessed and used to define optimal date of surgical resection, depending on patient responding status to treatment. Responding patients would undergo surgery at a later date than non-responders, in whom surgery could be performed earlier.
Benefits of the study lay in the more accurate definition of resection margins, with its associated potential therapeutic impact of the anal sphincter preservation and in the definition of the optimal date of rectal tumor resection, based on response status to radiochemotherapy.
Study interests are :
- Microscopic structure of tumor will be analyzed at the cellular and microvascular levels and compared to healthy mucosa.
- Evolution of response during and following radiochemotherapy will be assessed, and will help classify patients as responders/non responders.
- pCLE results will be compared to histopathology results on pre-treatment and resection biopsies.
- Images gathered through the imaging modalities (WLE, pCLE, EUS) along with histopathology results will be combined to create an atlas and database of rectal tumors.
Study design
- Primary purpose
- Diagnosis
- 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 (17 listed)
- Patient, male or female over 18 years old
- Patient with rectal adenocarcinoma :
- Absence of contra-indication to rectoscopy conduct
- Patient able to understand the study and to provide written informed consent
- Patient registered with the French social security regime
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Probe-based confocal laser endomicroscopyAlso: Cellvizio® with ColoFlex probePatients will undergo: * Conventional rectoscopy * pCLE exam following injection of fluorescein, fluorescent contrast agent * EUS : echoendoscopy * Biopsies for histopathology : location identical to those of pCLE * Tumor resection will be performed according to standard oncologic principles. All visible lesions will be documented. Both healthy and tumor tissue will be examined. Location of sites of interest will be documented on a schema, completed with photographs of endoscopic view. Biopsies will be harvested in both healthy and tumor tissue as well. After all procedures are complete, a second assessment of pCLE images by a third party will be performed. | Device | – |
| RectoscopyPatients will undergo: * Conventional rectoscopy * pCLE exam following injection of fluorescein, fluorescent contrast agent * EUS : echoendoscopy * Biopsies for histopathology : location identical to those of pCLE - Tumor resection will be performed according to standard oncologic principles. All visible lesions will be documented. Both healthy and tumor tissue will be examined. Location of sites of interest will be documented on a schema, completed with photographs of endoscopic view. Both healthy and tumor tissue will be examined. | Procedure or surgery | – |
| EUSAlso: EchoendoscopyPatients will undergo: * Conventional rectoscopy * pCLE exam following injection of fluorescein, fluorescent contrast agent * EUS : echoendoscopy * Biopsies for histopathology : location identical to those of pCLE - Tumor resection will be performed according to standard oncologic principles. All visible lesions will be documented. Both healthy and tumor tissue will be examined. Location of sites of interest will be documented on a schema, completed with photographs of endoscopic view. | Procedure or surgery | – |
| Biopsy and resectionPatients will undergo: * Conventional rectoscopy * pCLE exam following injection of fluorescein, fluorescent contrast agent * EUS : echoendoscopy * Biopsies for histopathology : location identical to those of pCLE * Tumor resection will be performed according to standard oncologic principles. All visible lesions will be documented. Both healthy and tumor tissue will be examined. Location of sites of interest will be documented on a schema, completed with photographs of endoscopic view. Biopsies will be harvested in both healthy and tumor tissue as well. | Procedure or surgery | – |
Primary outcome
Concordance in identification of lower pole of tumor
Time frame: Up to 9 months
Identification of lower pole of tumor will be compared between pCLE (optical images, virtual biopsies) and conventional histopathology (biopsies, postoperative analysis of resected piece). Samples of tumor tissue and closest tissue thought to be disease-free. Conventional biopsies and virtual biopsies prior to radiochemotherapy start (if applicable) and during surgery.
5 secondary outcomes
Identification of tissue characteristics
Time frame: Up to 9 months
Concordance of techniques (pCLE and histopathology)
Time frame: Up to 9 months
Comparison of pCLE results to EUS (echoendoscopy) results
Time frame: Upon surgery
Creation of an image bank
Time frame: Up to 9 months
Assessment of predictive value of interpretation criteria
Time frame: Up to 9 months
Results and safety
The study was stopped early (reason given: Difficulties with patients recruitment, study acceptance and protocol implementation.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2018.
- Results publication: PubMed 29732957Wijsmuller AR, Ghnassia JP, Varatharajah S, Schaeffer M, Leroy J, Marescaux J, Ignat M, Mutter D. Prospective Trial on Probe-Based Confocal Laser Endomicroscopy for the Identification of the Distal Limit in Rectal Adenocarcinoma. Surg Innov. 2018 Aug;25(4):313-322. doi: 10.1177/1553350618773011. Epub 2018 May 7.
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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.
Joël Leroy, Pr principal investigator
Service de Chirurgie Disgestive et Endocrinienne - Nouvel Hôpital Civil - Strasbourg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Probe-based confocal laser endomicroscopy, Rectoscopy and EUS in people with Rectal Cancer and Rectal Adenocarcinoma, run by IHU Strasbourg at 1 site in France.
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 17 inclusion and 0 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: stopped early, as of the sponsor's last update on 15 May 2018. 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 France. 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?
The study was stopped early (reason given: Difficulties with patients recruitment, study acceptance and protocol implementation.). 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?
Concordance in identification of lower pole of tumor (time frame: Up to 9 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 NCT01887509, which also lists 1 linked publication.
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 15 May 2018.