This study has been transitioned to CTIS with ID 2024-517718-13-00 check the CTIS register for the current data. Primary Objectives:To determine the optimal dose of the VEGF-targeting optical agent Bevacizumab-IRDye800CW for an adequate tumor-…
ID
Source
Brief title
Condition
- Metastases
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Degree of fluorescent signal levels (defined as TBR) per dose group, consisting
of the difference in signal levels
betweencolorectal PM and normal benign surrounding tissue.
Secondary outcome
Correlation of the ex-vivo fluorescent signal in colorectal PM and normal
tissue with histopathology and immunohistochemistry•
Macroscopic and real-time quantification of the fluorescent signal from
pathologically confirmed colorectal PM
Background summary
Carefully selected patients with colorectal peritoneal metastases (PM) can be
treated with curative intent by using
cytoreductivesurgery (CRS) with hyperthermic intraperitoneal chemotherapy
(HIPEC). One of the biggest challenges is to
adequately selectpatients who benefit the most from this aggresive treatment,
with acceptable treatment-related morbidity and
mortality. Theextent of peritoneal disease, described by the peritoneal cancer
index (PCI), is the most important prognostic factor
for survivaland is used in the selection process. At this moment, in our clinic
white-light diagnostic laparoscopy (WL-DLS)
remains thegolden standard to diagnose and assess the extent of colorectal PM.
Unfortunately, surgeons rely on visual
inspection alone andonly clinically suspected lesions will be biopsied. Small
peritoneal tumor lesions could be easily missed and
clinically suspiciouslesions could be benign leading to underestimating or
overestimating of the extent of colorectal PM.
Therefore, there is a clearneed for a diagnostic imaging modality that can
guide the oncological surgeon in the differentiation
between tumor and benigntissue intraoperatively to get a better view of the
extent of colorectal PM.
Molecular fluorescence-guided surgery (MFGS), a promising imaging technique for
real-time intraoperative tumor detection
byusing a tumor-targeted fluorescence tracer, could serve as a *red-flag*
imaging technique to assist in optimal tumor
identification.The tracer Bevacizumab-IRDye800CW with specific affinity to VEGF
(Vascular Endothelial Growth Factor) has
been developedfor fluorescence imaging to visual tumors in the operative and
endoscopic setting. VEGF is upregulated in 93%
of colorectal PM.The results of a feasibility study with Bevacizumab-IRDye800CW
at the UMCG including seven patients with
colorectal PM werevery promising. Fluorescence signals were observed in all
patients during exploratory laparotomy. All nonfluorescent
areasproved to be benign on final histopathology. In 27 out of 57 fluorescent
areas tumor tissue was identified. If
Bevacizumab-IRDye800CW is also feasible during DLS, which is a very different
setting compared to open surgery, it might
provide a moreaccurate investigation of the extent of peritoneal disease.
Ultimately, all of these strategies may reduce
overtreatment, morbidity,and costs while maintaining the same or better
effectiveness with a lower recurrence rate and improved
quality of life
Study objective
This study has been transitioned to CTIS with ID 2024-517718-13-00 check the CTIS register for the current data.
Primary Objectives:
To determine the optimal dose of the VEGF-targeting optical agent
Bevacizumab-IRDye800CW for an adequate tumor-tobackground
ratio (TBR) during white-light (WL) / fluorescence-guided (FG) diagnostic
laparoscopy (WL/FG-DLS) in colorectal
PM.
Secondary Objectives:
To correlate and validate ex-vivo fluorescence signals with histopathology and
immunohistochemistry;
To quantify sensitivity and specificity of Bevacizumab-IRDye800CW for
colorectal PM in order to make a power size
calculationfor a possible subsequent diagnostic accuracy study
Study design
The SELECT trial is a, non-randomized, non-blinded, prospective, single center
phase I feasibility study in patients with
suspicion of colorectal PM, looking at the safety profile and visibility of the
VEGF-targeted tracer Bevacizumab-IRDye800CW at
different doses during WL / FG-DLS. The aim is to find the dose group with the
best tumor to background ratio (TBR) incolorectal
PM during WL / FG-DLS. Two days prior to WL / FG-DLS, patients receive a single
dose Bevacizumab-
IRDye800CWintravenously. To study the safety of the tracer, hemodynamics will
be monitored for up to 15 minutes after
administration of the tracer. In this phase I dose-finding study, a 2x3 scheme
is chosen (2 doses with 3 patients in each dose
group). The single doses of Bevacizumab-IRDye800CW consist of: 4.5 mg (n = 3),
10 mg (n = 3). The first three patients receive
a single dose of 4.5 mg, the following three patients receive a dose of 10 mg.
After completion of the first six patients, the first
interim analysis will take place to assess the safety of the tracer and
determine the TBR of each dose group. The TBR is
calculated using the following formula: TBR = (tumorfluorescence) /
(surrounding tissue fluorescence). The dosage group with
the most optimal TBR will eventually be expanded to atotal of ten patients.
Study burden and risks
Burden: Intravenous administration of Bevacizumab-IRDye800CW two days prior to
WL / FG-DLS (+/- 30 minutes)• Estimated additional operation time of 30 minutes
during WL/FG-DLS.
Risks: Based on the observed toxicity profile in previous clinical trials, the
risks associated with the use of Bevacizumab-
IRDye800CW
Patients will have no direct benefit from this study. Surgery will be planned
as usual. During surgery, no decisions will be
madebased on the fluorescence imaging. The benefit of this study will be the
assessment of safety and the establishment
ofusefulness of Bevacizumab-IRDye800CW to identify colorectal PM during
WL/FG-DLS. The results from this study will be
atleast beneficial for other patients with cancer in the future.
Hanzeplein 1
Groningen 9713 GZ
NL
Hanzeplein 1
Groningen 9713 GZ
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
1) Age >= 18 years;
2) Patients with colorectal PM;
3) Scheduled to undergo CRS+HIPEC in the UMCG as part of standard care for
colorectal PM;
4) WHO performance score of 0-2;
5) Mentally competent person who is able and willing to comply with study
procedures;
6) Signed written informed consent;
7) For female subjects who are of childbearing potential, are premenopausal
with intact reproductive organs or are less than two years post-menopausal:
- A negative serum pregnancy test prior to receiving the tracer.
- Willing to ensure that she or her partner used effective birth control during
the trial and for three months thereafter.
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
1) Clinically advanced stage of colorectal PM, not suitable for CRS+HIPEC
confirmed by imaging (CT/PET);
2) Has been injected with another Investigational Medicinal Product (IMP)
within the past month;
3) Concomitant malignancies, except for adequately treated basocellular
carcinoma of the skin or in situ
carcinoma of the cervix uteri. Subjects with prior malignancies must be
disease-free for at least five years.
4) Clinically significant (i.e. active) cardiac disease (e.g. congestive heart
failure, symptomatic coronary artery disease and cardiac dysrhythmia) or
myocardial infarction within 12 months prior to enrolment;
5) Significant renal (creatinine>110µmol/L) dysfunction;
6) Previous allergic reaction to Bevacizumab;
7) Medical or psychiatric conditions that compromise the patient*s ability to
give informed consent;
8) Pregnancy or breast feeding;
9) Any significant change in their regular subscribed or not-subscribed
medication 14 days before tracer administration
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 |
|---|---|
| EU-CTR | CTIS2024-517718-13-00 |
| EU-CTR | CTIS2024-517718-13-01 |
| EudraCT | EUCTR2019-0001747-4-NL |
| CCMO | NL77451.042.21 |