Clinical trial NCT03699332: Multi-modality Imaging in Peritoneal Carcinomatosis of Colorectal Origin
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Peritoneal Carcinomatosis
Colorectal Cancer
Carcinoma
Neoplasms
Gastrointestinal Cancer
Keywords: image guided surgery
CRS
HIPEC
Fluorescence
Antibodies, monoclonal
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Dutch Cancer Society
First posted: 2018-10-09
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single Group Assignment
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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

Primary outcomes:
measure: Fluorescent signal at time of surgery
timeFrame: During cytoreductive surgery
Secondary outcomes:
measure: 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
timeFrame: 4 weeks
measure: Blood levels of the dual-labeled antibody
timeFrame: 60, 120 and 180 minutes after injection and 4 and 7 days after injection
measure: Optimal dose of the dual-labeled antibody preparation
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboudumc
Study officials:
affiliation: Radboud University Medical Center
name: JHW de Wilt, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: de Gooyer JM, Elekonawo FMK, Bremers AJA, Boerman OC, Aarntzen EHJG, de Reuver PR, Nagtegaal ID, Rijpkema M, de Wilt JHW. Multimodal CEA-targeted fluorescence and radioguided cytoreductive surgery for peritoneal metastases of colorectal origin. Nat Commun. 2022 May 12;13(1):2621. doi: 10.1038/s41467-022-29630-9.