FLUOPANC-trial - Fluorescence-guided Surgery of Pancreatic and Bileduct Tumors Using cRGD-ZW800-1

NCT05518071 | Completed Phase 2 DMC FDA Device

• 3 other identifiers: P21.1282019-004217-14NL 71219.058.22
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Pancreas as well as Cholangiocarcinoma have a dismal prognosis at time of diagnosis, due to late onset of clinical symptoms, patients present with advance disease. Complete surgical resection is the only potential curative treatment, however only a small percentage is eligible for upfront total surgical resection due to extension into anatomical related important vascular structures. Neoadjuvant chemo(radio)therapy has become the standard treatment modality for non-primary resectable disease (borderline resectable and locally advanced pancreatic cancer (LAPC)), where subsequent downstaging can make identification of the primary tumor more challenging during surgery. Near-infrared (NIR) fluorescence imaging can aid surgeons by providing real-time visualization of tumors, suspect lymph nodes and vital structures during surgery. Additional intra-operative feedback could possibly reduce the frequency of positive resection margins and increase complete removal of locally spread tumor and involved lymph nodes and could thereby improve patient outcomes as well as overall survival. cRGD-ZW800-1 is a targeted NIR-fluorophore, with specific binding capacity for integrins (αvβ3, αvβ5, αvβ6) which are overexpressed on tumor cells and tumor-associated vascular endothelium associated with neoangiogenesis.

Conditions

Pancreas Adenocarcinoma; Cholangiocarcinoma

Keywords

Fluorescence Guided Surgery; Pancreatic Ductal Adenocarcinoma; Extrahepatic cholangiocarcinoma; Near-Infrared (NIR) Fluorescence imaging; Novel fluorescent probe; cRGD-ZW800-1

Outcome Measures

Primary Outcomes (1)

• Visualization of the primary tumor using cRGD-ZW800-1 and dedicated NIR-Fluorescence imaging system.

  Visualization is measured using the tumor-to-background ratio (TBR) in in-vivo and ex-vivo setting. A tumor-to-background ratio (TBR) of at least ≥1.5 provides sufficient contrast for adequate visualization/delineation and will therefore be used as cut-off value.

  Surgery

Secondary Outcomes (5)

• Number and grade of treatment-emergent (serious) adverse events ((S)AEs).

  Enrollment - EOS

• Concordance between clinical assessment, histopathologic examination and NIR-Fluorescence imaging assessment of the resected tumor, lymph nodes and/or metastatic lesions and their histopathologic result.

  Surgery

• Define the optimal dose and dose interval of a single intravenous bolus injection of cRGD-ZW800-1.

  Enrollment - EOS

• Tumor positive margins detected with NIR fluorescence imaging using cRGD-ZW800-1, referenced to histopathology.

  Surgery

• Number of tumor-positive lymph nodes and metastases detected by NIR fluorescence imaging using cRGD-ZW800-1, referenced to histopathology.

  Surgery

Other Outcomes (1)

• Exploratory endpoint

  Surgery

Study Arms (5)

Cohort 1 - N=4 (0.05mg/kg, 2-4h before intervention)

EXPERIMENTAL

Drug: CRGD-ZW800-1; Device: Intraoperative near-infrared fluorescence imaging

Cohort 2 - N=4 (0.05mg/kg, 14-24h before intervention)

EXPERIMENTAL

Drug: CRGD-ZW800-1; Device: Intraoperative near-infrared fluorescence imaging

Cohort 3 - N=4 (0.025mg/kg, 2-4h before intervention)

EXPERIMENTAL

Drug: CRGD-ZW800-1; Device: Intraoperative near-infrared fluorescence imaging

Cohort 4 - N=4 (0.025mg/kg, 14-24h before intervention)

EXPERIMENTAL

Drug: CRGD-ZW800-1; Device: Intraoperative near-infrared fluorescence imaging

Expansion cohort - N=4 (optimal dose, optimal dose-interval)

EXPERIMENTAL

Drug: CRGD-ZW800-1; Device: Intraoperative near-infrared fluorescence imaging

Interventions

CRGD-ZW800-1 DRUG

Intravenous single bolus injection of the targeted NIR fluorophore cRGD-ZW800-1. This targeted 800nm zwitterionic fluorophore developed by the Hospital Pharmacy Department of LUMC consists of the fluorophore ZW800-1 conjugated to the cRGD peptide

Cohort 1 - N=4 (0.05mg/kg, 2-4h before intervention); Cohort 2 - N=4 (0.05mg/kg, 14-24h before intervention); Cohort 3 - N=4 (0.025mg/kg, 2-4h before intervention); Cohort 4 - N=4 (0.025mg/kg, 14-24h before intervention); Expansion cohort - N=4 (optimal dose, optimal dose-interval)

Intraoperative near-infrared fluorescence imaging DEVICE

Intraoperative imaging will be performed with at least one of the following CE-marked near-infrared (NIR) fluorescence imaging systems: Quest Spectrum imaging platform (v2/3.0) for open-procedures, the Olympus or Karl-Storz system for the diagnostic laparoscopy or the Intuitive Surgical Da Vinci Xi (Firefly-mode) for minimally invasive robot-assisted procedures. With a NIR-imaging system a potential fluorescent signal of the tumor can be evaluated. Furthermore, the Quest Spectrum platform will also be used for evaluation of ex-vivo fluorescence of resected tissue on the back table (Back table imaging) and pathology department (ex-vivo imaging), which shall be performed during and after every procedure.

Cohort 1 - N=4 (0.05mg/kg, 2-4h before intervention); Cohort 2 - N=4 (0.05mg/kg, 14-24h before intervention); Cohort 3 - N=4 (0.025mg/kg, 2-4h before intervention); Cohort 4 - N=4 (0.025mg/kg, 14-24h before intervention); Expansion cohort - N=4 (optimal dose, optimal dose-interval)

Eligibility Criteria

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

You may qualify if:

• Patients \> 18 years old;
• Patients scheduled and eligible for open/robotic resection because of (histologically proven) pancreatic carcinoma with or without neoadjuvant treatment. As well as patients scheduled and eligible for resection because of (histologically proven) distal or perihilar cholangiocarcinoma with or without neoadjuvant treatment.
• All women of childbearing potential and all males must practice effective contraception during the study and be willing and able to continue contraception for at least 30 days after their last dose of study treatment.
• Patients should be capable and willing to give informed consent before study specific procedures;

You may not qualify if:

• History of a clinically significant allergy or anaphylactic reactions;
• Patients with renal insufficiency (eGFR\<60 ml/min/1,73 m2);
• Patients with a previous kidney transplantation in the medical history;
• Pregnant women, or women giving breast feeding;
• Patients who are immunocompromised and do not have the ability to respond normally to an infection due to an impaired or weakened immune system, caused by either a pre-existing disease or concomitant medications (excluding intended neoadjuvant treatment);
• Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial;
• Any condition that the investigator considers to be potentially jeopardizing the patients well-being or the study objectives.

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (1)

Leiden University Medical Center

Leiden, 2300RC, Netherlands

Location

Related Publications (2)

• de Valk KS, Deken MM, Handgraaf HJM, Bhairosingh SS, Bijlstra OD, van Esdonk MJ, Terwisscha van Scheltinga AGT, Valentijn ARPM, March TL, Vuijk J, Peeters KCMJ, Holman FA, Hilling DE, Mieog JSD, Frangioni JV, Burggraaf J, Vahrmeijer AL. First-in-Human Assessment of cRGD-ZW800-1, a Zwitterionic, Integrin-Targeted, Near-Infrared Fluorescent Peptide in Colon Carcinoma. Clin Cancer Res. 2020 Aug 1;26(15):3990-3998. doi: 10.1158/1078-0432.CCR-19-4156. Epub 2020 Apr 28.

  PMID: 32345649 BACKGROUND

• Handgraaf HJM, Boonstra MC, Prevoo HAJM, Kuil J, Bordo MW, Boogerd LSF, Sibinga Mulder BG, Sier CFM, Vinkenburg-van Slooten ML, Valentijn ARPM, Burggraaf J, van de Velde CJH, Frangioni JV, Vahrmeijer AL. Real-time near-infrared fluorescence imaging using cRGD-ZW800-1 for intraoperative visualization of multiple cancer types. Oncotarget. 2017 Mar 28;8(13):21054-21066. doi: 10.18632/oncotarget.15486.

  PMID: 28416744 BACKGROUND

MeSH Terms

Conditions

Cholangiocarcinoma

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: dr. A.L. Vahrmeijer, MD, PhD

Study Record Dates

• First Submitted: August 24, 2022
• First Posted: August 26, 2022
• Study Start: November 9, 2022
• Primary Completion: May 23, 2024
• Study Completion: May 23, 2024
• Last Updated: June 24, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)