Multi-modality Imaging in Peritoneal Carcinomatosis of Colorectal Origin (MMIPC)

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

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Anticipated): 29
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands, 6525 GA
    • Recruiting
    • Radboudumc
    • Contact: Jan-Marie de Gooyer, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Dutch Cancer Society
• Investigators: Principal Investigator: JHW de Wilt, MD, PhD, Radboud University Medical Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2018
• Primary Completion (ANTICIPATED): March 1, 2021
• Study Completion (ANTICIPATED): September 1, 2021

Study Registration Dates

• First Submitted: October 5, 2018
• First Submitted That Met QC Criteria: October 5, 2018
• First Posted (ACTUAL): October 9, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 13, 2019
• Last Update Submitted That Met QC Criteria: September 12, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: HIPEC; Fluorescence; CRS; Antibodies, monoclonal; image guided surgery
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Peritoneal Diseases; Digestive System Neoplasms; Gastrointestinal Diseases; Abdominal Neoplasms; Carcinoma; Peritoneal Neoplasms; Gastrointestinal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Labetuzumab
• Other Study ID Numbers: NL57505.091.16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No