Hereditary Diffuse Gastric CancerNCT03950908
Biopsy Technique for Endoscopic Surveillance of Hereditary Diffuse Gastric Cancer
A study testing Single bite biopsy technique and Double bite biopsy technique in people with Hereditary Diffuse Gastric Cancer, run by University of Cambridge at 1 site in United Kingdom.
Trial summary
Germline mutation in e-cadherin gene (CDH1) is found in approximately 25% to 30% of individuals fulfilling the clinical criteria for hereditary diffuse gastric cancer (HDGC). Prophylactic gastrectomy is the mainstay of the management of cases with pathogenetic CDH1 mutation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hereditary Diffuse Gastric Cancer
- What is being tested?
- Single bite biopsy technique and Double bite biopsy technique
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 12 Oct 2017to 13 Dec 2018
- 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
- Patients in the Familial Gastric Cancer Registry held in Cambridge fulfilling clinical criteria for HDGC.
- Patients willing to undergo at least one upper GI endoscopy with random biopsies according to Cambridge biopsy protocol.
Who cannot join
- Patients who decline evaluation with endoscopy either as a screening or surveillance tool
- Patients on clopidogrel, and/or warfarin for high risk condition and unable to withhold temporarily the medication.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Single-bite Versus Double-bite Technique for Mapping Biopsies During Endoscopic Surveillance of Hereditary Diffuse Gastric Cancer: a Single Center, Randomized Controlled Trial
Germline mutation in e-cadherin gene (CDH1) is found in approximately 25% to 30% of individuals fulfilling the clinical criteria for hereditary diffuse gastric cancer (HDGC). Prophylactic gastrectomy is the mainstay of the management of cases with pathogenetic CDH1 mutation. However, some individuals refuse gastrectomy and prefer to delay it for medical or psychosocial reasons. For these patients as well as for those in which a pathogenetic mutation is not found, endoscopic surveillance is recommended. The suggested endoscopic protocol involves targeted as well as 30 random biopsies, which is tedious and time-consuming . In order to save time, two specimens can be taken during a single passage of the biopsy forceps ("double-bite" technique). The aim of this study was to determine the adequacy and utility of the "double-bite" technique in patients undergoing surveillance for HDGC as compared to the standard "single-bite technique".
Read the detailed description
Previous studies have validated endoscopy, as an efficient tool for initial screening and in selected cases surveillance of families fulfilling the clinical criteria for hereditary diffuse gastric cancer (HDGC). The aim is to detect microscopic foci of in situ or intramucosal signet ring cell carcinoma (SRCC), which are characteristic of early HDGC. Currently, the recommended endoscopic protocol involves targeted biopsies of any suspicious lesion as well as a minimum of 30 mapping random biopsies specimens taken from all anatomic areas of the gastric mucosa, also known as Cambridge endoscopy protocol. However this is a time-consuming and tedious process, which significantly prolongs the duration of the procedure and might reduce patient tolerance. In order to save time two specimens can be taken during a single passage of the forceps ("double-bite" technique).
In order to evaluate the adequacy and utility of the "double-bite" technique, patients undergoing surveillance for HDGC, are randomized to the single-bite vs double-bite arm. Endoscopies are performed according to a standardized protocol. Briefly, a white-light high-resolution endoscope with 85 magnification and a maximal resolution of 7.9 mm (GIF-FQ260Z; Olympus, Tokyo, Japan) is used to examine all anatomic segments of the insufflated stomach. Any abnormalities on white-light endoscopy are recorded and assessed further by narrow-band imaging magnification with or without autofluorescence imaging. Targeted biopsy specimens are taken from identified lesions, and 5 random biopsy specimens are taken in each of the siz gastric anatomical areas (prepylorus, antrum, transitional zone, body, fundus, and cardia). The double-bite technique involves taking an initial biopsy, repositioning the forceps, and taking another biopsy from the same area with the initial specimen still on the forceps. The single bite technique involves removing the forceps with its specimen after each individual biopsy. Time is recorded between the first and last random biopsy. Comfort score is reported after the procedure, according to the modified Gloucester scale. The investigators use Boston Single-Use Radial Jaw™ 4 biopsy forceps with a spike. Biopsy specimens are stained with hematoxylin and eosin and periodic acid-Schiff diastase and are assessed for size and presence of SRCC foci by an upper specialist GI pathologist, who have significant experience in SRCC identification. Any lesions are checked by a second pathologist within the Cambridge Pathology team before reporting. Both pathologists are blinded to study arm.
- Conditions
- Hereditary Diffuse Gastric Cancer
- Being tested
- Single bite biopsy technique, Double bite biopsy technique
- Medical subject headings
- Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Single bite biopsy techniqueOther
During biopsy collection one specimen will be retrieved during a single passage of the biopsy forceps.
Double bite biopsy techniqueOther
During biopsy collection two specimens will be retrieved during a single passage of the biopsy forceps.
| Study group | Role | What they receive |
|---|---|---|
| Single bite | Other | The single bite technique involved removing the forceps with its specimen after each individual biopsy. Receives: Other: Single bite biopsy technique |
| Double bite | Other | The double-bite technique involved taking an initial biopsy, repositioning the forceps, and taking another biopsy from the same area with the initial specimen still on the forceps. Receives: Other: Double bite biopsy technique |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of signet ring cell carcinoma (SRCC) foci.
Evaluating the diagnostic yield of the double-bite technique, by means of identifying SRCC foci, in comparison to the conventional single -bite arm.
Measured: 1 year
Secondary outcomes (4)
Time to perform biopsy protocol.
Differences between the study arms in terms of time required for biopsy collection
Measured: 1 year
Biopsy size
Differences between the study arms in terms of size of the biopsy specimens
Measured: 1 year
Patients comfort
Differences between the study arms in terms of patient comfort score, during the procedure. Comfort score is reported after the procedure, according to the modified Gloucester scale.
1: No discomfort - resting comfortably throughout; 2: Minimal. One or two episodes of mild discomfort, well tolerated; 3:Mild. More than 2 episodes of discomfort, adequately tolerated; 4: Moderate. Significant discomfort experienced several times during the procedure; 5: Severe. Extreme discomfort, experienced frequently during the procedure
Measured: 1 year
Dose of sedation.
Differences between the study arms in terms of dose required for sedation
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2019
- Study start12 Oct 2017
- Primary completion13 Dec 2018
- Study completion13 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Hereditary Diffuse Gastric 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cambridge
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Massimiliano di Pietro, MD, University of Cambridge
- Investigators
- Massimiliano di Pietro, MD, Principal investigator, MRC Cancer Unit.University of Cambridge.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03950908
- Sponsor's protocol ID
- FGCS protocol v.10
- Status last verified
- May 2019
- First submitted
- 13 May 2019
- Last updated
- 20 May 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
van der Post RS, Vogelaar IP, Carneiro F, Guilford P, Huntsman D, Hoogerbrugge N, Caldas C, Schreiber KE, Hardwick RH, Ausems MG, Bardram L, Benusiglio PR, Bisseling TM, Blair V, Bleiker E, Boussioutas A, Cats A, Coit D, DeGregorio L, Figueiredo J, Ford JM, Heijkoop E, Hermens R, Humar B, Kaurah P, Keller G, Lai J, Ligtenberg MJ, O'Donovan M, Oliveira C, Pinheiro H, Ragunath K, Rasenberg E, Richardson S, Roviello F, Schackert H, Seruca R, Taylor A, Ter Huurne A, Tischkowitz M, Joe ST, van Dijck B, van Grieken NC, van Hillegersberg R, van Sandick JW, Vehof R, van Krieken JH, Fitzgerald RC. Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J Med Genet. 2015 Jun;52(6):361-74. doi: 10.1136/jmedgenet-2015-103094. Epub 2015 May 15.
PubMed 25979631Mi EZ, Mi EZ, di Pietro M, O'Donovan M, Hardwick RH, Richardson S, Ziauddeen H, Fletcher PC, Caldas C, Tischkowitz M, Ragunath K, Fitzgerald RC. Comparative study of endoscopic surveillance in hereditary diffuse gastric cancer according to CDH1 mutation status. Gastrointest Endosc. 2018 Feb;87(2):408-418. doi: 10.1016/j.gie.2017.06.028. Epub 2017 Jul 6.
PubMed 28688938Fewings E, Larionov A, Redman J, Goldgraben MA, Scarth J, Richardson S, Brewer C, Davidson R, Ellis I, Evans DG, Halliday D, Izatt L, Marks P, McConnell V, Verbist L, Mayes R, Clark GR, Hadfield J, Chin SF, Teixeira MR, Giger OT, Hardwick R, di Pietro M, O'Donovan M, Pharoah P, Caldas C, Fitzgerald RC, Tischkowitz M. Germline pathogenic variants in PALB2 and other cancer-predisposing genes in families with hereditary diffuse gastric cancer without CDH1 mutation: a whole-exome sequencing study. Lancet Gastroenterol Hepatol. 2018 Jul;3(7):489-498. doi: 10.1016/S2468-1253(18)30079-7. Epub 2018 Apr 27.
PubMed 29706558Pappas A, Tan WK, Waldock W, Richardson S, Tripathi M, Januszewicz W, Roberts G, O'Donovan M, Fitzgerald RC, di Pietro M. Single-bite versus double-bite technique for mapping biopsies during endoscopic surveillance for hereditary diffuse gastric cancer: a single-center, randomized trial. Endoscopy. 2021 Mar;53(3):246-253. doi: 10.1055/a-1201-3125. Epub 2020 Jul 17.
PubMed 32679601
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single-bite Versus Double-bite Technique for Mapping Biopsies During Endoscopic Surveillance of Hereditary Diffuse Gastric Cancer: a Single Center, Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03950908
- Acronym / sponsor ID
- FGCS protocol v.10
- Conditions
- Hereditary Diffuse Gastric Cancer
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- University of CambridgeUniversity, hospital or other
- Study start
- 12 Oct 2017 (actual)
- Primary completion
- 13 Dec 2018 (actual)
- Study completion
- 13 Dec 2018 (actual)
- First posted
- 15 May 2019 (actual)
- 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.
Germline mutation in e-cadherin gene (CDH1) is found in approximately 25% to 30% of individuals fulfilling the clinical criteria for hereditary diffuse gastric cancer (HDGC). Prophylactic gastrectomy is the mainstay of the management of cases with pathogenetic CDH1 mutation. However, some individuals refuse gastrectomy and prefer to delay it for medical or psychosocial reasons. For these patients as well as for those in which a pathogenetic mutation is not found, endoscopic surveillance is recommended. The suggested endoscopic protocol involves targeted as well as 30 random biopsies, which is tedious and time-consuming . In order to save time, two specimens can be taken during a single passage of the biopsy forceps ("double-bite" technique). The aim of this study was to determine the adequacy and utility of the "double-bite" technique in patients undergoing surveillance for HDGC as compared to the standard "single-bite technique".
Detailed description
Previous studies have validated endoscopy, as an efficient tool for initial screening and in selected cases surveillance of families fulfilling the clinical criteria for hereditary diffuse gastric cancer (HDGC). The aim is to detect microscopic foci of in situ or intramucosal signet ring cell carcinoma (SRCC), which are characteristic of early HDGC. Currently, the recommended endoscopic protocol involves targeted biopsies of any suspicious lesion as well as a minimum of 30 mapping random biopsies specimens taken from all anatomic areas of the gastric mucosa, also known as Cambridge endoscopy protocol. However this is a time-consuming and tedious process, which significantly prolongs the duration of the procedure and might reduce patient tolerance. In order to save time two specimens can be taken during a single passage of the forceps ("double-bite" technique).
In order to evaluate the adequacy and utility of the "double-bite" technique, patients undergoing surveillance for HDGC, are randomized to the single-bite vs double-bite arm. Endoscopies are performed according to a standardized protocol. Briefly, a white-light high-resolution endoscope with 85 magnification and a maximal resolution of 7.9 mm (GIF-FQ260Z; Olympus, Tokyo, Japan) is used to examine all anatomic segments of the insufflated stomach. Any abnormalities on white-light endoscopy are recorded and assessed further by narrow-band imaging magnification with or without autofluorescence imaging. Targeted biopsy specimens are taken from identified lesions, and 5 random biopsy specimens are taken in each of the siz gastric anatomical areas (prepylorus, antrum, transitional zone, body, fundus, and cardia). The double-bite technique involves taking an initial biopsy, repositioning the forceps, and taking another biopsy from the same area with the initial specimen still on the forceps. The single bite technique involves removing the forceps with its specimen after each individual biopsy. Time is recorded between the first and last random biopsy. Comfort score is reported after the procedure, according to the modified Gloucester scale. The investigators use Boston Single-Use Radial Jaw™ 4 biopsy forceps with a spike. Biopsy specimens are stained with hematoxylin and eosin and periodic acid-Schiff diastase and are assessed for size and presence of SRCC foci by an upper specialist GI pathologist, who have significant experience in SRCC identification. Any lesions are checked by a second pathologist within the Cambridge Pathology team before reporting. Both pathologists are blinded to study arm.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Single bite | Other | Other: Single bite biopsy techniqueThe single bite technique involved removing the forceps with its specimen after each individual biopsy. |
| Double bite | Other | Other: Double bite biopsy techniqueThe double-bite technique involved taking an initial biopsy, repositioning the forceps, and taking another biopsy from the same area with the initial specimen still on the forceps. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients in the Familial Gastric Cancer Registry held in Cambridge fulfilling clinical criteria for HDGC.
- Patients willing to undergo at least one upper GI endoscopy with random biopsies according to Cambridge biopsy protocol.
Key exclusion criteria (2 listed)
- Patients who decline evaluation with endoscopy either as a screening or surveillance tool
- Patients on clopidogrel, and/or warfarin for high risk condition and unable to withhold temporarily the medication.
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 |
|---|---|---|
| Single bite biopsy techniqueDuring biopsy collection one specimen will be retrieved during a single passage of the biopsy forceps. | Other | Single bite |
| Double bite biopsy techniqueDuring biopsy collection two specimens will be retrieved during a single passage of the biopsy forceps. | Other | Double bite |
Primary outcome
Identification of signet ring cell carcinoma (SRCC) foci.
Time frame: 1 year
Evaluating the diagnostic yield of the double-bite technique, by means of identifying SRCC foci, in comparison to the conventional single -bite arm.
4 secondary outcomes
Time to perform biopsy protocol.
Time frame: 1 year
Biopsy size
Time frame: 1 year
Patients comfort
Time frame: 1 year
Dose of sedation.
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2019.
- Background: PubMed 25979631van der Post RS, Vogelaar IP, Carneiro F, Guilford P, Huntsman D, Hoogerbrugge N, Caldas C, Schreiber KE, Hardwick RH, Ausems MG, Bardram L, Benusiglio PR, Bisseling TM, Blair V, Bleiker E, Boussioutas A, Cats A, Coit D, DeGregorio L, Figueiredo J, Ford JM, Heijkoop E, Hermens R, Humar B, Kaurah P, Keller G, Lai J, Ligtenberg MJ, O'Donovan M, Oliveira C, Pinheiro H, Ragunath K, Rasenberg E, Richardson S, Roviello F, Schackert H, Seruca R, Taylor A, Ter Huurne A, Tischkowitz M, Joe ST, van Dijck B, van Grieken NC, van Hillegersberg R, van Sandick JW, Vehof R, van Krieken JH, Fitzgerald RC. Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J Med Genet. 2015 Jun;52(6):361-74. doi: 10.1136/jmedgenet-2015-103094. Epub 2015 May 15.
- Background: PubMed 28688938Mi EZ, Mi EZ, di Pietro M, O'Donovan M, Hardwick RH, Richardson S, Ziauddeen H, Fletcher PC, Caldas C, Tischkowitz M, Ragunath K, Fitzgerald RC. Comparative study of endoscopic surveillance in hereditary diffuse gastric cancer according to CDH1 mutation status. Gastrointest Endosc. 2018 Feb;87(2):408-418. doi: 10.1016/j.gie.2017.06.028. Epub 2017 Jul 6.
- Background: PubMed 29706558Fewings E, Larionov A, Redman J, Goldgraben MA, Scarth J, Richardson S, Brewer C, Davidson R, Ellis I, Evans DG, Halliday D, Izatt L, Marks P, McConnell V, Verbist L, Mayes R, Clark GR, Hadfield J, Chin SF, Teixeira MR, Giger OT, Hardwick R, di Pietro M, O'Donovan M, Pharoah P, Caldas C, Fitzgerald RC, Tischkowitz M. Germline pathogenic variants in PALB2 and other cancer-predisposing genes in families with hereditary diffuse gastric cancer without CDH1 mutation: a whole-exome sequencing study. Lancet Gastroenterol Hepatol. 2018 Jul;3(7):489-498. doi: 10.1016/S2468-1253(18)30079-7. Epub 2018 Apr 27.
- Derived from this study: PubMed 32679601Pappas A, Tan WK, Waldock W, Richardson S, Tripathi M, Januszewicz W, Roberts G, O'Donovan M, Fitzgerald RC, di Pietro M. Single-bite versus double-bite technique for mapping biopsies during endoscopic surveillance for hereditary diffuse gastric cancer: a single-center, randomized trial. Endoscopy. 2021 Mar;53(3):246-253. doi: 10.1055/a-1201-3125. Epub 2020 Jul 17.
- Individual participant dataSharing planned: No
Related trials for Hereditary Diffuse Gastric Cancer
RecruitingObservational study
CfDNA in Hereditary And High-risk Malignancies 2
Hereditary Cancer Syndrome
RecruitingObservational study
CTNNA1 Familial Expansion Study
Cancer Gene Mutation, Gastric Cancer
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.
Massimiliano di Pietro, MD principal investigator
MRC Cancer Unit.University of Cambridge.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Single bite biopsy technique and Double bite biopsy technique in people with Hereditary Diffuse Gastric Cancer, run by University of Cambridge 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 2 inclusion and 2 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: finished, as of the sponsor's last update on 20 May 2019. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Identification of signet ring cell carcinoma (SRCC) foci. (time frame: 1 year). 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 NCT03950908, which also lists 4 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 20 May 2019.