Head and Neck Cancer, Head and Neck Disorder
Conditions
Keywords
vocal fold immobility, electromyographic (EMG) monitoring, thyroidectomy, intraoperative nerve visualization
Brief summary
Bevonescein (ALM-488) is a novel fluorescein-containing peptide that is intended as a visualization adjunct for the real-time enhanced structural delineation of major nerves during Head and Neck surgery to potentially improve patient outcomes.
Detailed description
Patients with thyroid disease undergoing thyroidectomy will receive systemic administration of bevonescein pre-operatively for intraoperative visualization of nerves. The voice outcomes of these patients will be assessed pre-operatively and post-operatively using patient questionnaires. This study aims to show that improved nerve visualization with bevonescein will be associated with clinically meaningful improvement in voice outcomes compared to a previously published studies.
Interventions
DRUGBevonescein (ALM 488) Infusion
Bevonescein is a synthetic peptide of 17 amino acids conjugated to a fluorescein derivative (5-carboxyfluorescein \[FAM\]) and can be visualized using instruments suitable for visualizing fluorescein. Bevonescein selectively binds to extracellular matrix of nerve tissue, increasing nerve visibility and enhancing structure delineation of nerve tissue, potentially reducing the time needed for surgeons to identify nerve tissue and reducing likelihood of nerve injury during thyroidectomy surgery.
Sponsors
Matthew Spector
Alume Biosciences, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Scheduled to undergo hemi thyroidectomy or total thyroidectomy for thyroid disease, including neoplasm 2. Must be a minimum of 18 years old or older 3. Must be able to give documented informed consent to participate in this study 4. Must be a surgical candidate according to standard of care practices, as determined by the clinical judgement of the investigator 5. Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception prior to study entry and during the course of the study. An additional contraceptive method, such as a barrier method (e.g., condom), is required. In addition, men must agree not to donate sperm and women must agree not to donate eggs (ova, oocyte) for the purpose of reproduction during these same periods. 6. Female subjects of childbearing potential must not be pregnant or breastfeeding at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met: o Permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \> 45 years-of-age in the absence of other biological or physiological causes). Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff. 7. Willing and able to comply with all study procedures
Exclusion criteria
1. Previous history of surgery and/or radiation to the head, neck, or shoulder 2. Abnormal cardiac rhythm not controlled with medication 3. The patient has a history of drug-related anaphylactic or severe allergic reactions (CTCAE grade 3+), at the discretion of the treating investigator 4. Presence or history of any hypersensitivity to bevonescein (or fluorescein) or its excipients that, in the judgment of the investigator, places the patient at increased risk for adverse effects 5. Presence of a concurrent disease or condition that may interfere with study participation including recent (within 6 months of screening) NYHA Class III or IV heart failure, myocardial infarction (MI) or cerebrovascular accident (CVA) 6. Presence or history of any condition that, in the view of the Investigator, places the patient at high risk of poor treatment compliance or of not completing the study 7. Use of any Investigational Product or investigational medical device within 30 days prior to surgery date, or requirement for any investigational agent prior to completion of all scheduled study assessments 8. The subject has current evidence of renal disease defined as glomerular filtration rate (GFR) \< 60 mL/min/1.73 m2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Voice Handicap Index (VHI) scores | At baseline (before surgery) and at 28 days post-surgery | Mean change in Voice Handicap Index (VHI) scores pre-operatively and post-operatively. Voice Handicap Index (VHI) is a 30-item self-administered questionnaire divided equally into three subscales designed to measure a patient's perceived handicap related to their voice disorder across functional, physical, and emotional domains. Functional (F) subscale (10 items) evaluates how voice problems affect daily activities, work, and social interactions (difficulty being understood on the phone or professional duty limitations). Physical (P) subscale (10 items) addresses physical sensations or characteristics of the voice problem (vocal fatigue, strain, or pitch changes). Emotional (E) subscale (10 items) assesses the emotional impact of a voice disorder (frustration, embarrassment, or anxiety) related to voice use. Item scores range from 0 (never) to 4 (always), with higher scores indicating a greater perceived handicap. Total VHI score: 0 to 120 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to nerve identification In Thyroid Surgery | Day of Surgery | Time to nerve identification after the superior pole vessels are taken down, which starts once the superior pole of the thyroid lobe is taken down and stops once the nerve is visualized and confirmed via nerve monitoring device per surgeon preference. In thyroidectomy, the superior pole vessels (typically the superior thyroid artery and its branches) are often dissected and mobilized before proceeding to the superior laryngeal nerve (SLN) identification. The SLN runs in close proximity to the superior thyroid artery, and thus removing the vessel can help expose the nerve and reduce the risk of injury. Earlier identification allows for protection of the nerve before further dissection. |
| Visualization Scoring System (VSS) scores | Day of Surgery | Visualization Scoring System (VSS) is completed during the surgery based on the surgeon's visual assessment using the REVEAL 475 system when viewing the surgical field and the recurrent laryngeal nerve. The REVEAL device and supportive illumination system consists of the TriBeam light source (designed to create a 3-inch spot of white or blue light) and filter-modified surgical loupes. The VSS assessment comprises of a 4-point Likert scale for Nerve Conspicuity (NC) and Branching Delineation of the nerve as compared to its surrounding tissue. NC scores: 1- 'None', 2- 'Weak', 3- 'Clear' and 4- 'Clear and Bright'. Branching Delineation scores: 1- 'None', 2- 'Poorly visible', 3- 'Sufficiently visible' Clear' and 4- 'Excellent visibility'. Total scores: 1 to 32. Higher scores mean better visualization. |
| NERVE Questionnaire for Surgeons | Day of Surgery | The NERVE questionnaire, consisting of 9 qualitative questions will be completed at the end of the surgical procedure by the surgeon. The questions measure the surgeon's perceived Confidence, Branching (ability to assess the nerve during the procedure), Discrimination (nerve distinction), Trajectory (ability to assess the nerve trajectory), Depth of penetration (ability to assess the nerve as it goes beyond the surgical surface) Convenience, Ease of use (of Bevonescein), Added value (added benefit/value towards nerve identification and/or localization for this patient) and Satisfaction overall. Possible responses to each question: Very satisfied, Satisfied, Somewhat satisfied, Neither satisfied nor dissatisfied, Somewhat dissatisfied, Dissatisfied, Very dissatisfied. No numerical scoring scale. |
Countries
United States
Contacts
CONTACTJennifer Ruth
CONTACTMel J Mendez, BS, BS
PRINCIPAL_INVESTIGATORMatthew E Spector
UPMC Hillman Cancer Center
Outcome results
None listed