The aim of the study is to investigate whether SI-NET's can be visualized with Methylene Blue (MB) and near-infrared (NIR) fluorescence imaging.
ID
Source
Brief title
Condition
- Neoplastic and ectopic endocrinopathies
- Gastrointestinal therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is the Tumor to Background ratio (TBR). This is determined
on the primary tumor. A TBR> 2.0 is defined as 'feasible'. If this is the case
in at least 60% of the tumors, the method is defined as a success.
Secondary outcome
Determine the TBR of (lymph node) metastases
Determine the number of occult lesions found
Determine the optimal dose of MB
Determine the optimal time frame for the administration of MB
Determine confirmation of your signal with fluorescence microscopy
Background summary
Neuroendocrine tumors of the small intestine (SI-NET) are rare tumors. Patients
often do not present until distant metastases are already present in the
abdomen. Curative surgery is no longer possible for these patients. The
clinical problem is that it is often difficult to diagnose these distant
metastases. For this reason, the guidelines state to operate with a laparotomy
and then palpate and visualize the entire abdominal cavity. It is common for a
patient to undergo a laparotomy, after which it becomes clear that distant
metastases are present. It is decided not to continue the operation.
The aim of this study is to investigate whether a combination of intravenous
methylene blue and fluorescence imaging can visualize neuroendocrine tumors. If
this is possible, in the future it can be assessed with fluorescence by means
of laparoscopy whether distant metastases are present in the abdomen. In this
way, a group of patients can be sparred from an unnecessary laparotomy.
Moreover occult metastases can be identified for resection when curation is
possible.
Study objective
The aim of the study is to investigate whether SI-NET's can be visualized with
Methylene Blue (MB) and near-infrared (NIR) fluorescence imaging.
Study design
This is an open-label dose escalation study to investigate whether small
intestinal NETs can be visualized with MB and NIR. 17 patients will be included
who are eligible for resection of the SI-NET in Erasmus MC. Methylene blue will
be administered after the laparotomy. In the 10 minutes after that, a
standardized picture of the primary tumor will be taken every minute. The Tumor
to Background ratio will be measured on each of these photos. Furthermore,
pictures will be taken of the (lymph node) metastases. Surgical policy will not
change based on fluorescent imaging. Biopsies will be taken (if possible) of
fluorescence lesions that are not clinically suspected for metastases.
First, two groups of 5 patients will be included. The first group will receive
0.5 mg / kg MB, the second group will receive 1.0 mg/kg. After these 10
patients, an interim analysis will be performed to assess the optimal dose. The
last 7 patients will receive this optimal dose.
Intervention
After the laparotomy, 0.5 - 1.0 mg / kg MB will be administered. In the 10 - 15
minutes after that, images will be made of the tumor and possibly of the (lymph
node) metastases with a NIR camera.
Study burden and risks
The burden is deemed as 'nil'. MB is administered after anesthesia, so the
patient will not notice this. The operation takes about 15 minutes longer for
the study. After surgery, the study is finished for the patient. Methylene blue
is safe and registered as a medicine. Some patient groups have a higher risk of
toxicity and are therefore excluded (see exclusion criteria). In addition, this
toxicity has been reported in higher doses. MB is registrered for doses up to 7
mg / kg. In this study, a maximum of 1.0 mg / kg will be used.
Dr. Molewaterplein 40
Rotterdam 3015GD
NL
Dr. Molewaterplein 40
Rotterdam 3015GD
NL
Listed location countries
Age
Inclusion criteria
- Patients with lesions on the Galium-68-dotatate PET/CT scan suspected for a
Small intestine Neuro-endocrine tumor (SI-NET);
OR
- Patients with biopsy proven SI-NET;
AND
- With the primary SI-NET in situ
- >= 18 years of age;
- Before patient registration, written informed consent must be given according
to ICH/GCP, and national/local regulations.
Exclusion criteria
- Patients taking the following medication 30 days or less prior to surgery:
selective serotonin reuptake inhibitors (SSRI*s), serotonin noradrenalin
reuptake inhibitors (SNRI*s), tricyclic antidepressants (TCA*s), bupropion, or
buspiron.
- Use of serotonergic party drugs (MDMA, ecstasy, GHB, cocaine) 30 days or less
prior to surgery.
- Patients diagnosed with Glucose-6-Phosphate Dehydrogenase (G6DP) deficiency;
- Patients with a clinical significant history of allergic reaction to MB
- Patients who are pregnant or breastfeeding, female from childbearing
potential without adequate contraceptives.
- Incapacitated subjects.
- Any condition that the investigator, surgeon or anaesthesiologist considers
to be potentially jeopardizing the patient*s well-being or the study
objectives.
Design
Recruitment
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 |
|---|---|
| CCMO | NL75203.078.20 |