MMIPC: Multi-modality Imaging in Peritoneal Carcinomatosis of Colorectal Origin

Sponsor

Radboud University Medical Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT03699332

Collaborator

Dutch Cancer Society (Other)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Peritoneal Carcinomatosis Colorectal Cancer Carcinoma Neoplasms Gastrointestinal Cancer	Drug: Indium-111-DOTA-Labetuzumab-IRDye800CW injection Radiation: SPECT/CT scan Procedure: CRS extended with dual-modality imaging	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

29 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Single Group AssignmentSingle Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

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

Actual Study Start Date :

Dec 1, 2018

Anticipated Primary Completion Date :

Mar 1, 2021

Anticipated Study Completion Date :

Sep 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intraoperative multi-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.	Drug: Indium-111-DOTA-Labetuzumab-IRDye800CW injection Tracer injection Radiation: SPECT/CT scan Abdominal and thoracic SPECT/CT scan. Procedure: CRS extended with dual-modality imaging cytoreductive surgery will be performed extended with the use of dual-modality imaging.

Arm

Intervention/Treatment

Experimental: Intraoperative multi-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.

Drug: Indium-111-DOTA-Labetuzumab-IRDye800CW injection

Tracer injection

Radiation: SPECT/CT scan

Abdominal and thoracic SPECT/CT scan.

Procedure: CRS extended with dual-modality imaging

cytoreductive surgery will be performed extended with the use of dual-modality imaging.

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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