Multi-modality Imaging in Peritoneal Carcinomatosis of Colorectal Origin

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase I/II Study to Evaluate the Safety and Feasibility of Multi-modality Imaging Using Indium-111-DOTA-labetuzumab-IRDye800CW in Patients With Peritoneal Carcinomatosis of Colorectal Origin

Conditions
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Peritoneal Carcinomatosis, Colorectal Cancer, Carcinoma, Neoplasms, Gastrointestinal Cancer

Intervention / Treatment
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* Drug: Indium-111-DOTA-Labetuzumab-IRDye800CW injection
* Radiation: SPECT/CT scan
* Procedure: CRS extended with dual-modality imaging


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intraoperative multi-modality imaging<br>Patients receive a single intravenous dose of Indium-111-DOTA-Labetuzumab-IRDye800CW. At day 4 or 5 after antibody injection a SPECT/CT scan will be acquired. At day 6 or 7 standard of care cytoreductive surgery will be performed. This will be extended with the use of dual-modality imaging. | Drug: Indium-111-DOTA-Labetuzumab-IRDye800CW injection<br>* Tracer injection<br>Radiation: SPECT/CT scan<br>* Abdominal and thoracic SPECT/CT scan.<br>Procedure: CRS extended with dual-modality imaging<br>* cytoreductive surgery will be performed extended with the use of dual-modality imaging.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fluorescent signal at time of surgery | Can the tumor be identified by the fluorescent signal? Yes/No. Can the tumor be distinguished from normal tissue? Yes/No | During cytoreductive surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 | 4 weeks | 
| Blood levels of the dual-labeled antibody | 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) | 60, 120 and 180 minutes after injection and 4 and 7 days after injection | 
| Optimal dose of the dual-labeled antibody preparation | Optimal dose of dual-labeled antibody for dual modality image guided surgery | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CRS, image guided surgery, HIPEC, Fluorescence, Antibodies, monoclonal