Neoplasm, Skull Base Neoplasm
Conditions
Keywords
head and neck tumor, skull base tumor, neoplasm
Brief summary
This study allows head and neck cancer surgeons to specifically visualize cancerous cells apart from normal healthy tissue. 5-aminolevulinic acid (5-ALA) is a safe and effective FDA-approved agent successfully used by neurosurgeons for FGS of different brain tumors is given to the patients preoperatively. Using specific wavelengths of light as well as specialized magnified lenses the surgeons use this technique to assist in tumor resection.
Detailed description
Treatment for many head and neck cancer involves surgical resection, or removal, of the tumor. A potential outcome of surgery is subtotal resection, in which some cancerous material fails to be removed resulting in tumor recurrence and lower overall survival. Achieving total resection without interfering with normal tissue is a challenge due the critical anatomical structures of the head and neck. Fluorescent-guided surgery (FGS) is a new method of intraoperative imaging that can be used to clearly visualize cancerous tissue aprt from normal tissue during surgery in real-time. Before surgery, an agent that preferentially enters tumor cells is given to the patient. Tumor cells then glow brightly when exposed to specific wavelengths of light during surgery, allowing the surgeon to easily distinguish between healthy and cancerous tissue. 5-aminolevulinic acid (5-ALA) is a safe and effective FDA approved agent successfully used by neurosurgeons for FGS of different brain tumors which has not been assessed for use in head and neck cancers. The aim of the study is to determine if 5-ALA can be effectively used in FGS for different types of head and neck cancers, and if it will improve survival, tumor regrowth, and other outcomes for patients. 23 patients will be enrolled from the Mount Sinai Hospital, New York Eye and Ear Infirmary and Mount Sinai Union Square Faculty Practices over a 1 year period and will be completed by December 2022.
Interventions
The closure consists of colorless glass vial (Type II, Ph Eur) and bromobutyl-rubber stopper ø 20 mm (Type I, Ph Eur) and flip cap. The powder for oral solution is intended for single (partial) use. To prepare the ready-to-use solution the content of one vial is dissolved in 50 ml of water or apple juice. The concentration of the reconstituted solution is 3%. Gleolan® is administered orally to patients prior to tumor removal by surgery (20 mg/kg BW). The reconstituted solution may be prepared up to 24 hours prior to use if protected from light. It should be given 3 hours (range 3-5 hours) prior to planned induction of anesthesia for surgery, although its effect is present for up to 8-12 hours. This step is critical for an optimal visualization of tumor tissue due to pharmacokinetic properties of Gleolan®.
Sponsors
NX Development Corp
Icahn School of Medicine at Mount Sinai
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Subjects included in this trial must have had documentation of a new or recurrent head and neck or skull base tumor for which surgical resection is indicated and has been planned. These patients will include those with newly diagnosed or recurrent malignancies. * Age 18-80 * Karnofsky score \>60% * Subjects must have normal organ and marrow function as defined below: * leukocytes ≥ 3,000/mcL * absolute neutrophil count ≥ 1,500/mcL * platelets ≥ 100,000/mcl * total bilirubin within normal institutional limits * AST(SGOT)/ALT(SPGT) ≤ 2.5 X institutional upper limit of normal * creatinine within normal institutional limits OR Creatinine clearance \>60 mL/min/1.73m2 for patients with creatinine levels above institutional normal as defined per institution. * The effects of Gleolan® (5-ALA) on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. A pregnancy test will be performed for all women of childbearing ability prior to surgery (see
Exclusion criteria
below). Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * Ability to understand and the willingness to sign a written informed consent. * all upper aerodigestive head and neck cancers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Positive Test Result of PPIX Tissue Fluorescence | Through completion of surgery, up to 24 hours | The feasibility of using oral Gleolan® as an adjunct diagnostic imaging tool for malignant tumor tissue fluorescence will be primarily assessed by computing sensitivity of intraoperative Gleolan® induced PPIX tissue fluorescence. PPIX tissue fluorescence will be defined categorically as no (score 0), low (score 1), medium (score 2), and high (score 3) by operative surgeon, and images will be recorded. For purposes of computing measures of diagnostic performance a score of 0 will be considered a negative test result and a score of 1, 2 or 3 will be considered a positive test result. |
Countries
United States
Participant flow
Recruitment details
Enrollment was opened on 9/14/2021 and study was actively recruiting through Jan 14, 2025. The date of the last study visit was Dec 25, 2022. On Jan 14, 2025, the sponsor contacted the study team regarding closing the study. The study was officially closed on Feb 25, 2025.
Participants by arm
| Arm | Count |
|---|---|
| 5-aminolevulinic Acid Hydrochloride (Gleolan®) Gleolan® is available in colorless glass vials containing 1.5 g 5-aminolevulinic acid hydrochloride (Gleolan®) Gleolan® is administered orally to patients prior to tumor removal by surgery (20 mg/kg BW).
5-Aminolevulinic acid Hydrochloride: The closure consists of colorless glass vial (Type II, Ph Eur) and bromobutyl-rubber stopper ø 20 mm (Type I, Ph Eur) and flip cap. The powder for oral solution is intended for single (partial) use. To prepare the ready-to-use solution the content of one vial is dissolved in 50 ml of water or apple juice. The concentration of the reconstituted solution is 3%. Gleolan® is administered orally to patients prior to tumor removal by surgery (20 mg/kg BW). The reconstituted solution may be prepared up to 24 hours prior to use if protected from light. It should be given 3 hours (range 3-5 hours) prior to planned induction of anesthesia for surgery, although its effect is present for up to 8-12 hours. This step is critical for an optimal visualization of tumor tissue due to pharmacokinetic properties of Gleolan®. | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | 5-aminolevulinic Acid Hydrochloride (Gleolan®) |
|---|---|
| Age, Continuous | 60 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 2 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
Number of Participants With Positive Test Result of PPIX Tissue Fluorescence
The feasibility of using oral Gleolan® as an adjunct diagnostic imaging tool for malignant tumor tissue fluorescence will be primarily assessed by computing sensitivity of intraoperative Gleolan® induced PPIX tissue fluorescence. PPIX tissue fluorescence will be defined categorically as no (score 0), low (score 1), medium (score 2), and high (score 3) by operative surgeon, and images will be recorded. For purposes of computing measures of diagnostic performance a score of 0 will be considered a negative test result and a score of 1, 2 or 3 will be considered a positive test result.
Time frame: Through completion of surgery, up to 24 hours
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 5-aminolevulinic Acid Hydrochloride (Gleolan®) | Number of Participants With Positive Test Result of PPIX Tissue Fluorescence | 0 | 1 Participants |
| 5-aminolevulinic Acid Hydrochloride (Gleolan®) | Number of Participants With Positive Test Result of PPIX Tissue Fluorescence | 1 | 0 Participants |
| 5-aminolevulinic Acid Hydrochloride (Gleolan®) | Number of Participants With Positive Test Result of PPIX Tissue Fluorescence | 2 | 0 Participants |
| 5-aminolevulinic Acid Hydrochloride (Gleolan®) | Number of Participants With Positive Test Result of PPIX Tissue Fluorescence | 3 | 6 Participants |