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

• ClinicalTrials.gov Identifier: NCT03699332
• Recruitment Status: Unknown
• First Posted: October 9, 2018
• Last Update Posted: September 13, 2019
• Sponsor: Radboud University Medical Center
• Collaborator: Dutch Cancer Society
• Information provided by (Responsible Party): Radboud University Medical Center

Tracking Information

• First Submitted Date: October 5, 2018
• First Posted Date: October 9, 2018
• Last Update Posted Date: September 13, 2019
• Actual Study Start Date: December 1, 2018
• Estimated Primary Completion Date: March 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 5, 2018)

Fluorescent signal at time of surgery [ Time Frame: During cytoreductive surgery ]

Can the tumor be identified by the fluorescent signal? Yes/No. Can the tumor be distinguished from normal tissue? Yes/No

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 5, 2018)

• 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 4 weeks ]
  Optimal dose of dual-labeled antibody for dual modality image guided surgery

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Single Group Assignment

Masking: None (Open Label)
Primary Purpose: Diagnostic

Condition

• Peritoneal Carcinomatosis
• Colorectal Cancer
• Carcinoma
• Neoplasms
• Gastrointestinal Cancer

Intervention

• 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.

Study Arms

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.

Interventions:

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

• 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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: October 5, 2018): 29
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2021
• Estimated Primary Completion Date: March 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT03699332
• Other Study ID Numbers: NL57505.091.16
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Radboud University Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Radboud University Medical Center
• Original Study Sponsor: Same as current
• Collaborators: Dutch Cancer Society

Investigators

• Principal Investigator: JHW de Wilt, MD, PhD; Radboud University Medical Center

• PRS Account: Radboud University Medical Center
• Verification Date: September 2019