Clinical trial NCT04191460: Fluorescence-guided Surgery Using cRGD-ZW800-1 in Oral Cancer
Official title: Guided by Light: Optimizing Surgical Excision of Oral Cancer Using Real-time Fluorescence Imaging
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Squamous Cell Carcinoma of the Head and Neck
Oral Cancer
Squamous Cell Carcinoma of the Oral Cavity
Keywords: cRGD-ZW800-1
fluorescence-guided surgery
image-guided surgery
fluorescence imaging
cancer
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
First posted: 2019-12-09
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: DIAGNOSTIC

Brief summary: This is a two-staged clinical trial to investigate the feasibility of intraoperative Fluorescence Imaging (FLI) to adequately assess tumor margins in patients with oral cancer using cRGD-ZW800-1.

Detailed description: Work package I:

In WP-I, the preferred dose of the agent for imaging of margins in oral cancer will be determined. The signal-to-noise ratio will be determined in dose group A (n=7), which will receive 0.05 mg/kg of the tracer, 16-20 hours before surgery. After an interim evaluation of this ratio, the second dose group B (n=7) will receive either a higher or a lower dosage (to be determined) of the tracer. After inclusion of all patients (n=14), the dose with the highest intraoperative signal-to-noise ratio will be selected.

Work package II:

In WP-II, an expansion cohort (n=14) will be added to the group of patients that had received the selected dose in WP-I. In this group of 21 patients, it will be determined if FLI can improve the rate of adequate surgical resection margins. As secondary research questions, the following aspects will be assessed:

* sensitivity, specificity, positive and negative predictive values of FLI;
* colocalization with immunohistochemistry;
* change in surgical management; incremental operation time;
* FLI of excised cervical lymph nodes.

Eligibility criteria: Inclusion Criteria:

1. Patients with biopsy-proven squamous cell carcinoma of the oral cavity, eligible for surgical resection of the primary tumor;
2. ≥ 18 years of age;
3. Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations;
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.

Exclusion Criteria:

1. Previous surgery, chemotherapy or radiotherapy to the oral cavity;
2. History of a clinically significant allergy or anaphylactic reactions to any of the components of the agent.
3. Patients pregnant or breastfeeding, lack of effective contraception in male or female patients with reproductive potential;
4. Patients with renal insufficiency (eGFR\<60);
5. Patients with a previous kidney transplantation in the medical history;
6. Immuno-compromised 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;
7. Any condition that the investigator considers to be potentially jeopardizing the patient's well-being or the study objectives.

Primary outcomes:
measure: WP-I: (Highest) mean tumor-to-background ratio (TBR)
timeFrame: up to 48 ours post-dose
measure: WP-II: Rate of adequate (i.e. >5mm clear) tumor resection margins.
timeFrame: through histopathology, up to max 4 weeks post-op
Secondary outcomes:
measure: WP-II: Sensitivity, specificity, positive and negative predictive values
timeFrame: through histopathology, up to max 4 weeks post-op
measure: WP-II: Co-localization of FLI with immunohistochemistry on pathology slides
timeFrame: through histopathology, up to max 4 weeks post-op
measure: WP-II: Percentage of extra tissue resection based on FLI-driven frozen sections
timeFrame: through histopathology, up to max 4 weeks post-op
measure: WP-II: Operation time
timeFrame: through histopathology, up to max 4 weeks post-op
measure: WP-II: FLI of lymph node metastases after neck dissection
timeFrame: through histopathology, up to max 4 weeks post-op
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Center
state: Zuid-Holland
Study officials:
References: