Multi-modality Imaging in Peritoneal Carcinomatosis of Colorectal Origin

Phase 1

• Conditions: Gastrointestinal Cancer; Colorectal Cancer; Neoplasms; Peritoneal Carcinomatosis; Carcinoma
• Interventions: Drug: Indium-111-DOTA-Labetuzumab-IRDye800CW injection; Radiation: SPECT/CT scan; Procedure: CRS extended with dual-modality imaging

• Registration Number: NCT03699332
• Lead Sponsor: Radboud University Medical Center

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.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2018-10-05
• Study First Submitted QC: 2018-10-05
• Study First Posted: 2018-10-09
• Study Start: 2018-12-01
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-12
• Last Update Posted: 2019-09-13
• Primary Completion: 2021-03
• Study Completion: 2021-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

• Clinical diagnosis of peritoneal carcinomatosis of colorectal origin
• Scheduled for cytoreductive surgery and HIPEC.
• Age over 18 years
• Signed informed consent

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intraoperative multi-modality imaging	Indium-111-DOTA-Labetuzumab-IRDye800CW injection	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.
Intraoperative multi-modality imaging	CRS extended with dual-modality imaging	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.
Intraoperative multi-modality imaging	SPECT/CT scan	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
Optimal dose of the dual-labeled antibody preparation	4 weeks	Optimal dose of dual-labeled antibody for dual modality image guided surgery
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)

Trial Locations

Locations (1)

Radboudumc; 🇳🇱 Nijmegen, Netherlands