Intraoperative Dual-modality Imaging in Renal Cell Carcinoma

Study Overview
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Brief Summary
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Intraoperative tumor localization and resection can be enhanced using intraoperative fluorescence imaging and radiodetection. Girentuximab specifically recognizes carbonic anhydrase IX expressed on > 95% of renal cell carcinoma (RCC). Therefore Indium-111-DOTA-girentuximab-IRDye800CW is a perfect dual-labeled antibody for dual-modality image-guided surgery in RCC. The aim of this study is to assess the feasibility and safety of intraoperative dual-modality imaging with Indium-111-DOTA-girentuximab-IRDye800CW in renal cell carcinoma patients.

Detailed Description
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In oncologic surgery complete tumor resection is important for treatment outcome and patient survival. 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. Girentuximab specifically recognizes carbonic anhydrase IX expressed on > 95% of renal cell carcinoma (RCC). Therefore Indium-111-DOTA-girentuximab-IRDye800CW is a perfect dual-labeled antibody for dual-modality image-guided surgery in RCC. The concept has been shown in preclinical studies with mice and the investigators will translate this to the clinic. Eligible patients with renal cell carcinoma scheduled for (partial) nephrectomy will receive dual-labeled girentuximab 7 days before surgery. At day 4 or 5 a SPECT/CT of the abdomen will be obtained. 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-girentuximab-IRDye800CW in renal cell carcinoma.

Official Title
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A Phase 1 Study to Evaluate the Safety and Feasibility of Intraoperative Detection of Clear Cell Renal Cell Carcinoma Using Indium-111-DOTA-girentuximab-IRDye800CW

Conditions
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Carcinoma, Renal Cell

Intervention / Treatment
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* Drug: Indium-111-DOTA-Girentuximab-IRDye800CW
* Radiation: SPECT/CT
* Procedure: Intraoperative dual-modality imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of clear cell renal cell carcinoma planned for surgery, (partial) nephrectomy Performance status: Karnofsky 70 % Being fit for surgery Minimum age 18 years Signed informed consent Exclusion Criteria: A known subtype other than clear cell RCC Any medical condition present that in the opinion of the investigator will affect patients' clinical status. Administration of a radioisotope within 10 physical half lives prior to study enrollment Pregnancy and lactation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intraoperative dual-modality imaging<br>Patients receive a single intravenous dose of Indium-111-DOTA-Girentuximab-IRDye800CW. At day 4 or 5 after antibody injection a whole body planar scan and SPECT/CT scan will be acquired. At day 7 standard of care (partial) nephrectomy will be performed. This will be extended with the use of dual-modality imaging. | Drug: Indium-111-DOTA-Girentuximab-IRDye800CW<br>* Indium-111-DOTA-Girentuximab-IRDye800CW tracer injection will be administered 7 days before (partial) nephrectomy<br>* Other names: Dual-labeled girentuximab;Radiation: SPECT/CT<br>* 4 or 5 days after tracer injection a SPECT/CT of the abdomen will be acquired.<br>Procedure: Intraoperative dual-modality imaging<br>* 7 days after dual-labeled girentuximab injection standard of care surgery will be performed extended with the use of dual-modality imaging.<br>* Other names: Fluorescence and radioguided surgery;|

What is the study measuring?
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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 surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | The number of participants with grade 3 or 4 Adverse Events according to CTCAE v4.0 will be scored. | 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 | Tumor to background ratio will be evaluated for each dose. | 4 weeks |