Cetuximab-IRDye 800CW and Intraoperative Imaging in Finding Pancreatic Cancer in Patients Undergoing Surgery

NCT ID: NCT02736578

Last Updated: 2019-06-25

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

8 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-07-31

Study Completion Date

2017-05-22

Brief Summary

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This phase 1-2 trial studies the side effects and best dose of cetuximab-IRDye 800CW when used with intraoperative imaging, to determine the utility of cetuximab-IRDye 800CW to identify and assess pancreatic cancer in patients undergoing surgery to remove the tumor. Cetuximab-IRDye 800CW may help doctors better identify cancer in the operating room by making the cancer visible when viewed through a fluorescent imaging system.

Detailed Description

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This is a dose-escalation study of 50 mg or 100 mg cetuximab-IRDye800.

Clearance of the tumor margin during surgical resection of pancreatic cancer is clinical importance, as margin-positive resections are suspected to be associated with rapid emergence of distant metastases shortly after surgery. However, pancreatic cancer is known to be difficult to visualize intraoperatively. Nonetheless, better detection of tumor tissue might improve the rate of complete tumor clearance, thereby improving outcomes. However, in order to be actionable, the data from such enhanced tumor detection must be available during the resection procedure. This study evaluates the use of a dye, Cetuximab-IRDye 800CW, that is administered pre-surgery, and is detectable during the surgical procedure.

Florescent Imaging Cetuximab is a chimeric (mouse/human) monoclonal antibody that targets the epidermal growth factor (EGF) receptor (EGFR). EGFR is highly-expressed in pancreatic ductal adenocarcinoma (PDAC) and is a good target for antibody-mediated imaging, due to its transmembrane position. Cetuximab-IRDye 800CW is cetuximab labeled with IRDye800, an N-hydroxysuccinimide (NHS) ester infrared dye. IRDye800 has very similar properties compared to indocyanine green, and indocyanine green is readily detectable with a number of imaging systems. This study evaluates the Cetuximab-IRDye 800CW as a intraoperative labeling agent.

Patients receive Cetuximab-IRDye 800CW intravenously (IV) at 50 mg or 100 mg over 30 minutes to 1 hour on day 0. Within 2 to 5 days, patients undergo surgery with intraoperative imaging. Cetuximab-IRDye 800CW is used as part of a tumor-targeted molecular imaging procedure operating on the principles of differential accumulation of the antibody-dye conjugate in pancreatic tumor tissue vs normal pancreatic tissue vs pancreatitis tissue.

Excised tissues are prepared as formalin-fixed paraffin-embedded (FFPE) blocks for assessment of fluorescent intensity.

Photoacoustic imaging (PAI) For purposes of non-quantitative comparison, photoacoustic imaging (PAI) of the tumor lesions is also conducted. PAI refers to a non-invasive evaluation by ultrasound of the area of the resected tumor and surrounding tissue. PAI may have special utility for detecting tumors within 5 to 7 mm of depth, with a high degree of spatial resolution, which might be useful to enhance generation of tumor-free surgical margins. PAI does not utilize ionizing radiation, and should complement and conform to the findings from the fluorescent imaging.

PRIMARY OBJECTIVE:

Determine the efficacy of cetuximab-IRDye800 in intraoperatively identifying pancreatic cancer compared to surrounding normal pancreatic and extrapancreatic tissue, as measured by tumor-to-background ratio.

SECONDARY OBJECTIVE:

Determine the tolerability of the cetuximab IRDye800 as an imaging agent in patients undergoing resection of pancreatic cancer.

Conditions

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Pancreatic Adenocarcinoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Cetuximab IRDye800, 50 mg

On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 50 mg, followed by surgery with intraoperative imaging within 2 to 5 days.

Group Type EXPERIMENTAL

Cetuximab-IRDye800

Intervention Type DRUG

Administered intravenously (IV) at 50 or 100 mg

Cetuximab

Intervention Type DRUG

Administered as a 100 mg IV loading dose

Cetuximab IRDye800, 100 mg

On day 0, participants receive a 100 mg cetuximab loading dose by intravenous infusion (IV), followed 1 hour later by cetuximab-IRDye 800CW IV at 100 mg, followed by surgery with intraoperative imaging within 2 to 5 days.

Group Type EXPERIMENTAL

Cetuximab-IRDye800

Intervention Type DRUG

Administered intravenously (IV) at 50 or 100 mg

Cetuximab

Intervention Type DRUG

Administered as a 100 mg IV loading dose

Interventions

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Cetuximab-IRDye800

Administered intravenously (IV) at 50 or 100 mg

Intervention Type DRUG

Cetuximab

Administered as a 100 mg IV loading dose

Intervention Type DRUG

Other Intervention Names

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Cetuximab-IRDye 800CW Erbitux C225

Eligibility Criteria

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Inclusion Criteria

* Clinically suspected or biopsy confirmed diagnosis of pancreatic adenocarcinoma
* Planned standard of care surgery with curative intent for pancreatic adenocarcinoma
* ≥ 19 years of age
* Life expectancy of more than 12 weeks
* EITHER

* Karnofsky performance status of at least 70%, OR
* Eastern Cooperative Oncology Group (ECOG)/Zubrod level 1
* Hemoglobin ≥ 9 gm/dL
* Platelet count ≥ 100,000/mm\^3
* Magnesium \> the lower limit of normal (LLN) per institution normal lab values
* Potassium \> LLN
* Calcium \> LLN
* Thyroid-stimulating hormone (TSH) \< 13 micro International units/mL

Exclusion Criteria

* Received an investigational drug within 30 days prior to first dose of cetuximab IRDye800
* Myocardial infarction (MI); cerebrovascular accident (CVA); uncontrolled congestive heart failure (CHF); or unstable angina within 6 months prior to enrollment
* History of infusion reactions to cetuximab or other monoclonal antibody therapies
* Pregnant or breastfeeding
* Evidence of QT prolongation on pretreatment electrocardiography (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
Minimum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Eben Rosenthal

OTHER

Sponsor Role lead

Responsible Party

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Eben Rosenthal

Professor of Otolaryngology

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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George Poultsides, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

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Stanford University School of Medicine

Stanford, California, United States

Site Status

Countries

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United States

References

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Rosenthal EL, Kulbersh BD, King T, Chaudhuri TR, Zinn KR. Use of fluorescent labeled anti-epidermal growth factor receptor antibody to image head and neck squamous cell carcinoma xenografts. Mol Cancer Ther. 2007 Apr;6(4):1230-8. doi: 10.1158/1535-7163.MCT-06-0741.

Reference Type BACKGROUND
PMID: 17431103 (View on PubMed)

Rosenthal EL, Kulbersh BD, Duncan RD, Zhang W, Magnuson JS, Carroll WR, Zinn K. In vivo detection of head and neck cancer orthotopic xenografts by immunofluorescence. Laryngoscope. 2006 Sep;116(9):1636-41. doi: 10.1097/01.mlg.0000232513.19873.da.

Reference Type BACKGROUND
PMID: 16954995 (View on PubMed)

Tummers WS, Miller SE, Teraphongphom NT, Gomez A, Steinberg I, Huland DM, Hong S, Kothapalli SR, Hasan A, Ertsey R, Bonsing BA, Vahrmeijer AL, Swijnenburg RJ, Longacre TA, Fisher GA, Gambhir SS, Poultsides GA, Rosenthal EL. Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging. Ann Surg Oncol. 2018 Jul;25(7):1880-1888. doi: 10.1245/s10434-018-6453-2. Epub 2018 Apr 17.

Reference Type RESULT
PMID: 29667116 (View on PubMed)

Lwin TM, Hoffman RM, Bouvet M. The future of tumour-specific fluorescence-guided surgery for pancreatic cancer. Lancet Gastroenterol Hepatol. 2020 Aug;5(8):715-717. doi: 10.1016/S2468-1253(20)30123-0. Epub 2020 May 14. No abstract available.

Reference Type DERIVED
PMID: 32416765 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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NCI-2016-00433

Identifier Type: REGISTRY

Identifier Source: secondary_id

PANC0024

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA124435

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB-35789

Identifier Type: -

Identifier Source: org_study_id

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