Image Guided Surgery for Margin Assessment of Head and Neck Cancer Using Cetuximab-IRDye800CW cONjugate

NCT03134846 | Unknown Phase 1

• 1 other identifier: NL58585.042.16
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 1

Brief Summary

Surgery remains a main pillar in the treatment of head and neck squamous cell carcinoma (HNSCC). The margin status is the main prognostic factor of local tumor control in surgically treated HNSCC and will determine the postoperative treatment strategy. A margin of ≤1 mm of normal tissue is considered a positive margin and requires either a re-operation or postoperative chemoradiation with a combination of cisplatin and 5-FU, which substantially increases morbidity. Margins wider than 1 mm but less than 5 mm require re-operation, or, if that is not possible, post-operative radiotherapy without the concomitant use of chemotherapy. Currently, no technology is available in the operating room, which reliably supports tumor excision in terms of margin status. In fact, surgeons can only combine pre- operative imaging data with tactile and visual information during surgery for assessing tumor margins with limited accuracy. With the introduction of molecular imaging techniques using near infrared (NIR) fluorescent optical contrast agents coupled to targeted compounds, new avenues have opened up for intra-operative assessment of tumor margins. Tracers are based on antibodies directed against Vascular Endothelial Growth Factor-A, i.e. bevacizumab-IRDye800CW, in patients with breast cancer or against Epidermal Growth Factor Receptor, i.e. cetuximab-IRDye800CW, in patients with HNSCC. First trials have shown that systemic administration of these compounds is safe and tumor specific. These findings prompted us to design this innovative application in a clinical trial for the intraoperative assessment of tumor margins during surgical treatment of HNSCC using cetuximab-IRDye800CW.

Conditions

Head and Neck Squamous Cell Carcinoma; Margin Assessment

Keywords

Intraoperative fluorescence imaging; Cetuximab-IRDye800CW; Molecular imaging

Outcome Measures

Primary Outcomes (2)

• Phase 1: Determine the optimal dose of Cetuximab-IRDye800CW for imaging

  The primary endpoint for the feasibility study (9 patients) will be confirmation of the clinically applicable dose of cetuximab-IRDye800CW. The aim is to obtain at least a TBR higher than 2 by fluorescence imaging with the intra operative camera. This number has been found to give sufficient demarcation of tumor to normal tissue on wide field images.

  Five months

• Phase 2: Threshold level of fluorescence

  Determine a threshold level of fluorescence that can discriminate between EGFR distribution in normal tissue and a margin with EGFR-positive tumor.

  Three years

Secondary Outcomes (5)

• Phase 1: Secondary outcome: Safety

  Five months

• Phase 1: Secondary outcome: Identification of positive margins

  Five months

• Phase 1: Tissue specificity of IRDye800cw

  Five months

• Phase 1: Histological location of IRDye800cw

  Five months

• Phase 2: Secondary outcome: Minimal thickness of the non-fluorescent margin

  Three years

Study Arms (6)

Phase 1: 10mg Cetuximab-IRDye800CW

EXPERIMENTAL

Three patients will receive 10mg Cetuximab-IRDye800cv I.V. four days prior to surgery.

Drug: Cetuximab-IRDye800CW

Phase 1: 25mg Cetuximab-IRDye800CW

EXPERIMENTAL

Patients will receive 25mg Cetuximab-IRDye800cv I.V. four days prior to surgery.

Drug: Cetuximab-IRDye800CW

Phase 1: 50 mg Cetuximab-IRDye800CW

EXPERIMENTAL

Patients will receive 50mg Cetuximab-IRDye800cv I.V. four days prior to surgery.

Drug: Cetuximab-IRDye800CW

Phase 1: 75mg cetuximab + 15 mg Cetuximab-IRDye800CW

EXPERIMENTAL

Patients will receive 75mg cetuximab + 15 mg Cetuximab-IRDye800CW I.V. four days prior to surgery.

Drug: Cetuximab-IRDye800CW

Phase 1: 75mg cetuximab + 25 mg Cetuximab-IRDye800CW

EXPERIMENTAL

Patients will receive 75mg cetuximab + 25 mg Cetuximab-IRDye800CW I.V. four days prior to surgery.

Drug: Cetuximab-IRDye800CW

After having established the optimal cetuximab-IRDye800CW dose

EXPERIMENTAL

After having established the optimal cetuximab-IRDye800CW dose we will extent the study by including up to 70 patients for this specific dose (as determined in phase 1).

Drug: Cetuximab-IRDye800CW

Interventions

Cetuximab-IRDye800CW DRUG

Pre-operatively administration of Cetuximab-IRDye800CW for intra operative margin assessment using a fluorescent antibody-based optical tracer

Also known as: Cetuximab-800cw

After having established the optimal cetuximab-IRDye800CW dose; Phase 1: 10mg Cetuximab-IRDye800CW; Phase 1: 25mg Cetuximab-IRDye800CW; Phase 1: 50 mg Cetuximab-IRDye800CW; Phase 1: 75mg cetuximab + 15 mg Cetuximab-IRDye800CW; Phase 1: 75mg cetuximab + 25 mg Cetuximab-IRDye800CW

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Biopsy confirmed diagnosis of primary or recurrent HNSCC and scheduled to undergo surgical resection as decided by the Multi-Disciplinary Head and Neck Tumor Board of the UMCG.
• Age ≥ 18 years
• Written informed consent
• Adequate potential for follow up
• Acceptable hematologic status, kidney function, and liver function, as standard surgery protocol requires.

You may not qualify if:

• Medical or psychiatric conditions that compromise the patient's ability to give informed consent
• Concurrent uncontrolled medical conditions.
• Received an investigational drug within 30 days prior to the dose of cetuximab-IRDye800CW
• Tumors at sites of which the surgeon would assess that in vivo imaging would not be feasible
• Had within 6 months prior to enrollment: myocardial infarction, cerebrovascular accident, uncontrolled cardiac heart failure, significant liver disease, unstable angina
• Inadequately controlled hypertension with or without current antihypertensive medications.
• History of infusion reactions to cetuximab or other monoclonal antibody therapies
• Pregnant or lactating women. Documentation of a negative pregnancy test must be available for women of childbearing potential. Woman of childbearing potential are premenopausal women with intact reproductive organs and women less than two years after menopause.
• Evidence of QT prolongation on pretreatment ECG (greater than 440 ms in males or greater than 450 ms in females)
• Lab values that in the opinion of the primary surgeon would prevent surgical resection.
• Patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents.
• Magnesium, potassium and calcium lower than the lower limit of normal range.
• Life expectancy \< 12 weeks
• Karnofsky performance status \< 70%

Sponsors & Collaborators

• University Medical Center Groningen: lead
• UMC Utrecht: collaborator
• Erasmus Medical Center: collaborator

Study Sites (1)

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

RECRUITING

Related Publications (1)

• de Wit JG, Vonk J, Voskuil FJ, de Visscher SAHJ, Schepman KP, Hooghiemstra WTR, Linssen MD, Elias SG, Halmos GB, Plaat BEC, Doff JJ, Rosenthal EL, Robinson D, van der Vegt B, Nagengast WB, van Dam GM, Witjes MJH. EGFR-targeted fluorescence molecular imaging for intraoperative margin assessment in oral cancer patients: a phase II trial. Nat Commun. 2023 Aug 16;14(1):4952. doi: 10.1038/s41467-023-40324-8.

  PMID: 37587149 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Central Study Contacts

Max J.H. Witjes, MD, PhD

CONTACT

+31-50-3613841; m.j.h.witjes@umcg.nl

Floris J. Voskuil, MD

CONTACT

+31-50-3655170; f.j.voskuil@umcg.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Model Details: Phase 1: 3x3 Dose-escalation with 3 different doses Cetuximab-IRDye800CW Phase 2: Prospective cross sectional diagnostic study. After having established the optimal cetuximab-IRDye800CW dose we will extent the study by including up to 70 patients.

Study Record Dates

• First Submitted: April 20, 2017
• First Posted: May 1, 2017
• Study Start: December 16, 2017
• Primary Completion: December 1, 2021
• Study Completion: June 1, 2022
• Last Updated: May 3, 2021

Record last verified: 2021-04

Locations

NL (1)