No registrations found.
ID
Source
Brief title
Health condition
Gastroenteropancreatic neuroendocrine neoplasms
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. No. of (serious) adverse events and suspected unexpected serious adverse reactions;
2. Identify the dose with the optimal tumour-to-background ratio;
3. Ex vivo validation of targeted uptake by tumour tissue by histopathology.
Secondary outcome
1. Comparison of no. of (additionally) identified (metastatic) GEP-NENs using intraoperative fluorescent imaging compared to preoperative 68Ga-DOTATATE PET imaging and histopathological examination;
2. Complete removal of tumour tissue.
Background summary
Rationale: Currently, preoperative imaging of GEP-NENs is conducted using 68Ga-DOTATATE, which makes use of the overexpressed somatostatin type 2 receptors (SSTR-2) on cell surfaces of GEP-NENs. PHT001 is proved to be able to clearly delineate tumour boundaries in vitro on human biospecimens of NENs. Successful implementation PHT001 in clinical practice is therefore expected to aid in adequate and complete removal of tumour cells, identify malignant lymph nodes and distant metastases.
Objective: The aim of this study is to produce and implement a SSTR-2 targeted fluorescent tracer and assess its safety and best dose to accurately identify gastroenteropancreatic neuroendocrine neoplasms during surgical resection.
Study design: Phase 0 microdosing study.
Study population: Patients undergoing surgery for GEP-NEN.
Intervention: Patients will receive a bolus injection of MMC(IRDye800CW)-TOC.
Main study end-points:
• No. of (serious) adverse events and suspected unexpected serious adverse reactions;
• Identify the dose with the optimal tumour-to-background ratio;
• Ex vivo validation of targeted uptake by tumour tissue by histopathology.
Study objective
MMC(IRDye800CW)-TOC is safe to inject in patients for intraoperative visualization of gastroenteropancreatic neuroendocrine neoplasms
Study design
Primary outcomes:
1. SAEs will be assessed within 30 days after administration of the IMP, and will be graded according to CTCAR v5.0;
2. Optimal dose will be assessed after acquiring and analyses of images using ImageJ software;
3. Ex vivo validation will be assessed by comparing tissue slides with H&E, anti-SSTR2 and fluorescence microscopy using the Nikon Ti2 microscope or Odyssey CLx device.
Secondary outcomes:
1. Comparison of new lesions will be made postoperatively by correlating intraoperative finding with the pre-operative PET-CT images;
2. Complete removal of tumour tissue will be assessed by the pathologist postoperatively.
The overall follow-up period is 30 days.
Intervention
Single bolus injection of PHT001
Inclusion criteria
• Patients undergoing surgery for a primary GEP-NEN (stomach, duodenum, ampulla of Vater, pancreas, jejunum, ileum, colon or rectum), of any stage, grade and intent (i.e. curative/palliative) or metastases of a GEP-NEN;
• SSTR-2 positive disease, as proven by a DOTATATE PET scan pre-operatively (conducted at location AMC and part of standard care);
• Age of 18 years and older;
• Written informed consent.
Exclusion criteria
• NEN, not meeting the inclusion criteria (non-GEP-NEN, unknown location);
• Pregnant or breast-feeding women;
• Known hypersensitivity to the investigational medicinal product (IMP) or any of its components;
• Patients with an allergic/infusion reaction to 1 mg of TOC test dose of the unlabelled TOC;
• Patients with known allergies to intravenous radiographic contrast agents;
• Patients who have not provided a signed informed consent form to participate in the study, prior to the start of any protocol related activities;
• Patients who, within the last 30 days, have participated in any clinical study of a therapeutic agent which may interfere with the safety or efficacy analysis of the IMP;
• Serious non-malignant disease (e.g. psychiatric infectious, autoimmune, metabolic, renal, hepatic, cardiovascular or hematological), that may interfere with the objectives of the study or with the safety of the subject, as judged by the investigator;
• A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms);
• A history of additional risk factors for torsade de pointes (e.g., heart failure, hypokalaemia, family history of Long QT Syndrome);
• The use of concomitant medications that prolong the QT/QTc interval.
Design
Recruitment
IPD sharing statement
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 |
|---|---|
| NTR-new | NL9298 |
| Other | METC AMC : Pending |