Primary ObjectivesTo assess the efficacy of 0.13mg/kg EMI-137 IV injection to detect lesions during colonoscopy, in subjects at high suspicion of developing colorectal cancer by:- Comparing the number of pathological lesions detected with WL with…
ID
Source
Brief title
Condition
- Gastrointestinal neoplasms malignant and unspecified
- Gastrointestinal therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Detection of additional pathological lesions using WL+ FL compared to WL only
- Fluorescence signal of lesions
- TBR signal, defined as fluorescent signal of the lesion compared to
fluorescence signal
of tissue surrounding the lesion
- Concordance of fluorescence intensity and lesions with different pathological
lesion statuses and C-Met expression.
Secondary outcome
Safety and tolerability endpoints
- Treatment-emergent (serious) adverse events ((S)AEs).
- Concomitant medication
- Clinical laboratory tests
o Haematology
o Chemistry
o Urinalysis
- Vital signs
o Pulse Rate (bpm)
o Systolic blood pressure (mmHg)
o Diastolic blood pressure (mmHg)
o Body temperature ( *C )
- Presence of injection site reactions
Pharmacokinetic endpoints
Pharmacokinetics will be assessed by a single, in vivo, spectroscopy derived,
quantitative measurement of the lesion (target) and normal bowel tissue
(background). These parameters will later be converted to a target to
background ratio.
Background summary
Colorectal cancer (CRC) is a major cause of cancer death, and colonoscopy is
firmly established as the mainstay of CRC prevention and detection. Technical
aspects of endoscopic imaging have a major role in determining polyp detection
rates. Imaging at colonoscopy is currently performed using white light (WL),
which is not optimal for detection of smaller and non-polypoid lesions, leading
to miss rates of up to 25%. Optical imaging, using agents that targets
(pre)malignant lesions coupled to a fluorescent dye, could improve polyp
detection during colonoscopy.
Study objective
Primary Objectives
To assess the efficacy of 0.13mg/kg EMI-137 IV injection to detect lesions
during colonoscopy, in subjects at high suspicion of developing colorectal
cancer by:
- Comparing the number of pathological lesions detected with WL with the number
of lesions detected with WL+FL
- Investigating the concordance of fluorescence intensity and histologic status.
- Establishing target to background ratio (TBR) of fluorescent lesions.
Secondary Objectives
- To assess the safety and tolerability of 0.13mg/kg EMI-137 iv injection;
- To assess the practical application of the technique, e.g.
o Ease of use of the fluorescence colonoscopy
o Ease of use of EMI-137 for injection;
- To assess the tissue pharmacokinetics of a single IV injection of 0.13mg/kg
EMI-137 by in vivo quantification of fluorescence signals in polyps and normal
tissue by spectroscopy using 2 colonoscopes;
- To assess the optimal time window between dose administration and
fluorescence imaging (stage 1);
- To assess c-MET expression and fluorescence on fluorescence microscopy in
biopsied lesions.
Study design
Open-label, single dose, phase IIb, multicenter study in patients with a
suspicion of colorectal cancer undergoing colonoscopy. Colonoscopy will be
performed using white light (WL) and fluorescence light (FL) with the order in
which WL or WL/FL will be randomized per subject.
Intervention
fluorescence guided colonoscopy after EMI-137 administration.
Study burden and risks
The risks of participation for the patients in the trial include
hypersensitivity reactions and an increased risk of bowel perforation. These
risks are deemed minimal. Nevertheless precautionary measures (supervised
administration by qualified staff and availability of medical treatment to
treat hypersensitivity reactions) are in place and these effects are generally
well manageable. The extra burden of the trial is minimal, the research will
for the largest part coincide with routine care and the proposed procedures. We
therefore believe this research that, could possibly provide a useful tool to
find (more) malignant lesions and possibly improves patient outcome, is
justified.
Nine Edinburgh BioQuarter, Little France Road 9
Edinburgh EH16 4UX
GB
Nine Edinburgh BioQuarter, Little France Road 9
Edinburgh EH16 4UX
GB
Listed location countries
Age
Inclusion criteria
1. Signed informed consent prior to any study-mandated procedure;
2. Healthy male or female subjects aged 18 years or older;
3. Female subjects need to be either surgically sterile (has had a documented bilateral
oophorectomy and/or documented hysterectomy), post-menopausal (cessation of
menses for more than 1 year), or pre-menopausal with a negative urine pregnancy test
performed at screening and a negative urine pregnancy test performed within 24 hours
of administration of EMI-137 Injection. Pre-menopausal female subjects should also
employ an effective method of birth control up to 90 days after EMI-137 administration. Barrier contraceptives must be used throughout the study in both sexes.
4. The subject has a positive FOB test or clinical suspicion on colorectal cancer and is scheduled to undergo a colonoscopy.
5. The subject has a normal or clinically acceptable medical history, physical examination,
and vital signs findings at screening (within 35 days prior to administration of study
drug).
6. The subject*s screening ECG and clinical laboratory tests are within normal limits, or if
any are outside of normal limits they are considered to be clinically insignificant.
Exclusion criteria
1. If female, the subject is lactating or pregnant.
2. The subject is being treated or has been treated with chemotherapy or radiation within
the 3 months before enrolment.
3. A biopsy has been obtained from the colon within the 3 weeks before enrolment.
4. The subject has been previously included in this study or another fluorescence IMP.
5. Treatment with another IMP within 3 months prior to screening or more than 4 times in
the past year.
6. Loss of blood outside the limits of Sanquin within 3 months prior to screening.
7. The subject has had any significant change in their regular prescription or non-prescription medication between 14 days and 1 day prior to EMI-137 administration.
8. The subject has a history of alcohol and/or drug abuse within the previous 12 months.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-002827-27-NL |
| CCMO | NL58475.056.16 |