To assess the feasibility of cRGD-ZW800-1 to visualize tumors in real-time using dedicated NIR fluorescence imaging systems
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint
To determine the sensitivity of NIR fluorescence imaging with cRGD-ZW800-1
Secondary outcome
Secondary endpoints
To define the optimal dose of cRGD-ZW800-1 for intraoperative near-infrared
fluorescence imaging of tumors.
To assess safety and tolerability of single doses of cRGD-ZW800-1.
Background summary
Accurate and real-time detection of tumors during surgery remains challenging.
Sensitivity of available imaging modalities is often
inadequate with respect to margin or metastasis detection. Following SPECT and
PET agents, tumor targeted ligands can also be
conjugated to NIR (near-infrared, 700-900 nm) fluorophores and being visualized
using specific intraoperative near-infrared imaging
systems. Traditionally, NIR fluorophores have been developed for a variety of
preclinical applications, including labeling to specific
ligands, and can be used to understand the fate of intravenously administered
anticancer therapeutics, in determining biodistribution,
tissue penetration and cellular localization. Currently, NIR fluorescent
labeled vehicles are also being used as a diagnostic tool for
accurate localization of cancer cells in real-time during surgery.
Here we study cRGD-ZW800-1, a cyclic pentapeptide (cRGD) conjugated to the 800
nm NIR fluorophore ZW800-1. The cyclic
3-amino acid sequence (RGD) is clinically a well-known peptide that binds to
various integrins (αvβ1, αVβ3, αvβ5, αvβ6, αvβ8, α5β1,
α8β1 and αIIbβ3), mostly associated with neoangiogenesis. Tumors larger than
1-2 mm depend on the formation of new blood
vessels to acquire sufficient amounts of oxygen and nutrients. Some of these
integrins are therefore overexpressed on malignant
cells and in tumor stroma, for example in breast, colorectal, pancreas and lung
cancer. RGD based molecules have already been
investigated in various phase I and phase II imaging studies using PET and
SPECT and in a phase III study as an anticancer therapy
(cilengitide).
Extensive preliminary work on the cRGD-ZW800-1 agent has been performed by our
group and showed clear delineation of
melanomas and colorectal, liver, pancreatic, lung, and head and neck tumors in
xenograft mouse models while due to its renal
clearance route also ureters could be recognized.
Study objective
To assess the feasibility of cRGD-ZW800-1 to visualize tumors in real-time
using dedicated NIR fluorescence imaging systems
Study design
This is an exploratory study to evaluate the diagnostic value of fluorescent
imaging using cRGD-ZW800-1 in patients with primary rectal and sigmoid cancer
undergoing a low anterior resection at the Leiden University Medical Center.
The study will consist of 18 patients, spread out over 4 cohorts where three
different doses of cRGD-ZW800-1 will be explored to select the optimal dose for
surgery. The selected doses are based on the pre-clinical and phase I results.
cRGD-ZW800-1 will be administered in a bolus injection at least two hours prior
to surgery as follows:
Cohort 1 (up to 4 patients): 0.005 mg/kg cRGD-ZW800-1
Cohort 2 (up to 4 patients): 0.015 mg/kg cRGD-ZW800-1
Cohort 3 (up to 4 patients): 0.050 mg/kg cRGD-ZW800-1
Cohort 4 (up to 6 patients): 0.050 mg/kg cRGD-ZW800-1 (optimal dose)
Study burden and risks
The risks to subjects related to cRGD-ZW800-1 are not completly known yet. In
the phase 1 study, 11 healthy volunteers were administered cRGD-ZW800-1 without
signs of acute or chronic toxicity.
Other risks to subjects mainly relate to the i.v. injection and venous blood
sampling. Intravenous injection and the use of cannulas (1 cannula for i.v.
injection and 1 cannula for venous blood sampling) are known to carry a small
risk of infection and hematoma. Based on consistent observations in the
preclinical efficacy and safety pharmacology studies, it is expected that
discoloration of the skin and urine may occur. Based on experience with other
fluorescent probes, it cannot be excluded that hypersensitivity reactions may
occur, although there are no indications for cRGD-ZW800-1.
There are no expected direct benefits to subjects who participate in this
trial. Participants may help others prospectively by contributing to the
knowledge base for designing future studies to evaluate the use of cRGD-ZW800-1
administration in patients undergoing oncologic surgery.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
1) Patients > 18 years old;
2) Patients scheduled and eligible for resection because of colorectal
carcinoma without any other clinically significant co-morbidity that can
potentially jeopardize the patient well-being (judged by principal
investigator);
3) Patients should be capable and willing to give informed consent before study
specific procedures;
4) Screening ECG and clinical laboratory test results are within normal limits,
or if any are outside of normal limits they are considered to be clinically
insignificant;
5) The patient has a normal or clinically acceptable medical history, physical
examination, and vital signs findings at screening;
6) Absence 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.
Exclusion criteria
1) History of a clinically significant allergy or anaphylactic reactions;
2) Patients pregnant or breastfeeding, lack of effective contraception in male
or female patients with reproductive potential;
3) Patients with renal insufficiency (eGFR<60)
4) Patients with a previous kidney transplantation in the medical history
5) Immunocompromised patients who do not have the ability to respond normally
to an infection due to an impaired on weakened immune system, caused by either
a pre-existing disease or concomitant medications.
6) Any condition that the investigator considers to be potentially jeopardizing
the patients well-being or the study objectives.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-002772-60-NL |
| CCMO | NL62508.058.17 |