This study has been transitioned to CTIS with ID 2024-519750-36-00 check the CTIS register for the current data. The primary aim of this study is to determine the feasibility of using intraoperative fluorescence-imaging (FLI) to identify laryngeal…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
- Head and neck therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary study endpoint of WP-1 is the tumor-to-background ratio (TBR) of
laryngeal or pharyngeal tumours with fluorescence imaging after cRGD-ZW800-1
administration. The primary endpoint of WP-II is the number of clear resection
margins.
Secondary outcome
1. Sensitivity, specificity and positive predictive value of FLI;
2. The intraoperative change in surgical management based on FLI;
3. FLI of excised cervical lymph nodes;
4. Influence of previous radiotherapy on the FLI performance;
5. Adverse events and toxicity after intravenous injection with cRGD-ZW800-1;
Background summary
Head and neck cancer (HNC) is the 9th most common tumor worldwide. Thirty-five
percent of these tumors arise in the larynx or hypopharynx. Depending on the
(anticipated) remaining organ function, advanced staged (stage III/IV)
laryngeal- or hypopharyngeal cancer (LHC) is treated with concomitant
chemoradiotherapy or a total laryng-(opharyng)ectomy (TL(P)). A complete
resection of these tumors is the most important surrogate marker for survival.
Clear tumor margins increase survival, lower local tumor recurrence rates and
reduce the need for burdensome adjuvant therapies (addition of chemotherapy to
postoperative radiotherapy). Moreover, precise margin delineation is imperative
in the delicate head and neck region where wider resections inevitably lead to
increased morbidity and loss of functionality.
Unpublished data from our medical centre showed positive resection margins in
42% (larynx) and 58% (hypopharynx) after TL(P) in patients treated between 2000
and 2019. These data clearly illustrate the need for new intraoperative
visualization techniques to assess tumor margins in real-time and to guide
surgical removal of LHC with clear surgical margins while retaining maximal
functionality.
Study objective
This study has been transitioned to CTIS with ID 2024-519750-36-00 check the CTIS register for the current data.
The primary aim of this study is to determine the feasibility of using
intraoperative fluorescence-imaging (FLI) to identify laryngeal and
hypopharyngeal cancer during TL(P).
Study design
This is an open-label, single-dose, prospective clinical trial. The study
comprises 2 work packages. The main objective of work package I (WP-1) is to
assess feasibility of FLI during TL(P) and to assess the optimal dose of the
fluorescent tracer. Work package II (WP-II) is designed to assess whether FLI
can detect and decrease tumor positive margins after a TL(P).
Intervention
Patients will receive an intravenous injection of cRGD-ZW800-1 at least 2h
prior to surgery. Standard surgical procedure will be performed. After surgery,
FLI will be performed on the wound bed and specimen. Wound bed tissue with
fluorescence positive signal will additionally resected if the surgeon decides
it is *clinical suspect* for malignant tissue. When fluorescent tissue would be
clinically unsuspected for malignancy, biopsies or frozen sections will be
taken. Clinically unsuspected tissue will only be biopsied if it does not
causes any harm to the patient.
Study burden and risks
The risks of participation for patients in the trial include adverse
(hypersensitivity) reactions. These risks are deemed minimal. In the rare case
that hypersensitivity occurs, the effects are generally well manageable.
cRGD-ZW800-1 is extensively tested preclinically as well as in healthy
volunteers. Next, it was found to be safe in the first clinical trial with
colorectal cancer patients (section 6). Finally, the first work package of the
*Guided by Light*-trial, a clinical study using this tracer in oral cancer
patients (n=14) at the Erasmus MC, was completed very recently. In this study,
no adverse events occurred that were related to the drug, nor did any toxicity
or hypersensitivity reactions occur. Nevertheless, precautionary measures are
in place, including supervised administration by qualified staff and
availability of medical treatment to treat hypersensitivity reactions. Patients
will undergo additional measurements of vital functions, ECG and laboratory
testing after administration.
The benefits for study participants include a potentially higher chance of
clear tumor margins. Clear tumor margins increase survival, lower local tumor
recurrence rates, and may reduce the need for burdensome adjuvant therapies
(chemotherapy and radiotherapy).
Doctor Molewaterplein 14
Rotterdam 3015GD
NL
Doctor Molewaterplein 14
Rotterdam 3015GD
NL
Listed location countries
Age
Inclusion criteria
- Patients with biopsy-proven squamous cell LHC, eligible for surgical
resection of the tumor by TL(P);
- >= 18 years of age;
- Written informed consent must be obtained;
- Sufficient knowledge of the Dutch language to understand the informed consent
form;
Exclusion criteria
- History of a clinically significant allergy or anaphylactic reactions to any
of the components of the agent;
- Other synchronous biopsy proven malignancies currently active, except for
adequately treated in situ carcinomaof cervix and basal or squamous cell skin
carcinoma;
- Patients pregnant or breastfeeding, lack of effective contraception in male
or female patients with reproductivepotential;
- Patients with renal insufficiency (defined as eGFR<60);
- Patients with previous kidney transplantation or a solitary functioning kidney
- Immuno-compromised patients who do not have the ability to respond normally
to an infection due to an impairedor weakened immune system, caused by either a
pre-existing disease or concomitant medications;
- Patients using medications that may significantly impair renal function (i.e.
NSAIDs, particularly COX-2inhibitors), that cannot be paused during the course
of the study;
- Patients with ASA classification of 4 or higher;
- Patients with measured QTc of 500 ms or higher at screening;
- Patients with laboratory abnormalities defined as:
o Aspartate AminoTransferase, Alanine AminoTransferase, Gamma Glutamyl
Transferase) or AlkalinePhosphatase levels above 5 times the ULN or;
o Total bilirubin above 3 times the ULN or;
o Platelet count below 100 x 109/L or;
o Hemoglobin below 4 mmol/L (females) or below 5 mmol/l (males).
- Incapacitated subjects
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EU-CTR | CTIS2024-519750-36-00 |
| EudraCT | EUCTR2020-003474-45-NL |
| CCMO | NL74742.078.21 |