Carcinoma, Colorectal Cancer, Gastrointestinal Cancer, Neoplasms, Peritoneal Carcinomatosis
Conditions
Keywords
image guided surgery, CRS, HIPEC, Fluorescence, Antibodies, monoclonal
Brief summary
Intraoperative tumor localization and resection can be enhanced using intraoperative fluorescence imaging and radiodetection. Labetuzumab specifically recognizes CEA which is is expressed on \> 95% of colorectal cancers.. Therefore Indium-111-DOTA-labetuzumab-IRDye800CW is a perfect dual-labeled antibody for dual-modality image-guided surgery in peritoneal carcinomatosis of colorectal cancer.
Detailed description
In oncologic surgery complete tumor resection is important for treatment outcome and patient survival. When performing cytoreductive surgery (CRS) for peritoneal carcinomatosis of colorectal origin it can sometimes be difficult to distinguish tumor deposits from adhesions and scar tissue. Intraoperative tumor localization and resection can be enhanced using intraoperative imaging techniques (e.g. targeted radioguided or fluorescence guided surgery). A powerful synergy can be achieved by combining radiotracers (e.g. Indium-111) and optical tracers (e.g. IRDye 800CW) conjugated to an antibody against a tumor-associated antigen. Labetuzumab specifically recognises CEA which is expressed on \> 95% of all colorectal cancers. Therefore Indium-111-DOTA-labetuzumab-IRDye800CW is a perfect dual-labeled antibody for dual-modality image-guided surgery in peritoneal carcinomatosis of colorectal origin. The concept has been shown in preclinical studies with mice and the investigators will translate this to the clinic. Eligible patients with peritoneal carcinomatosis of colorectal origin scheduled for CRS + HIPEC will receive dual-labeled labetuzumab 6-7 days before surgery. At day 4 or 5 a SPECT/CT of the abdomen and thorax will be obtained. Cytoreductive surgery at day 7 will be extended with the use of a near-infrared fluorescence camera and a gamma probe. The aim of this study is to assess the feasibility and safety of intraoperative dual-modality imaging with Indium-111-DOTA-labetuzumab-IRDye800CW in peritoneal carcinomatosis of colorectal cancer.
Interventions
DRUGIndium-111-DOTA-Labetuzumab-IRDye800CW injection
Tracer injection
RADIATIONSPECT/CT scan
Abdominal and thoracic SPECT/CT scan.
PROCEDURECRS extended with dual-modality imaging
cytoreductive surgery will be performed extended with the use of dual-modality imaging.
Sponsors
Dutch Cancer Society
Radboud University Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Single Group Assignment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of peritoneal carcinomatosis of colorectal origin * Scheduled for cytoreductive surgery and HIPEC. * Age over 18 years * Signed informed consent
Exclusion criteria
* Any medical condition present that in the opinion of the investigator will affect patients clinicals status * Administration of a radionuclide within 10 physical half-lives prior to study enrollment * Pregnancy or lactation * Patients with very high (\>500ng/ml serum CEA levels * Known CEA negative tumor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fluorescent signal at time of surgery | During cytoreductive surgery | Can the tumor be identified by the fluorescent signal? Yes/No. Can the tumor be distinguished from normal tissue? Yes/No |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of dual-labeled antibody (labetuzumab) as assessed by the number of participants with grade 3 or 4 Adverse Events according to CTCAE v4.0 | 4 weeks | Safety of dual-labeled antibody injection as assessed by the number of participants with grade 3 or 4 Adverse Events according to CTCAE v4.0 |
| Blood levels of the dual-labeled antibody | 60, 120 and 180 minutes after injection and 4 and 7 days after injection | Blood samples will be measured for radioactivity in a gamma counter at different timepoints after injection. This will be expressed as percentage injected dose per gram (%ID/g) |
| Optimal dose of the dual-labeled antibody preparation | 4 weeks | Optimal dose of dual-labeled antibody for dual modality image guided surgery |
Countries
Netherlands
Contacts
Primary ContactFMK Elekonawo, MD
Backup ContactJM de Gooyer, MD
Outcome results
None listed