Clinical Study
Our technology has been validated in study after study and we continue to pursue active research to further new formulation development and confirm benefit in disease indices where we can have a positive impact.
NEO100-02 Meningioma Study
NeOnc has begun its open-label Phase 2 study focusing on NEO100’s ability to have a therapeutic impact on residual, progressive, and recurrent high-grade instances of meningioma, the most common form of primary brain tumors. The study is currently recruiting candidates and will be working to determine the impact of NEO-100 on the trial candidates’ progression-free- and overall-survival rates.
The Impact of Meningioma
Meningiomas are a type of tumor that originates in the meninges, the layers of tissue covering the brain and spinal cord. These tumors are generally slow-growing and usually benign, meaning they are not cancerous. However, in some cases, they can be aggressive or malignant. Survival and treatment for those with malignant and recurring meningioma brain tumors are very poor. Currently, meningioma accounts for 40% of all primary brain tumors. More than 170,000 people are diagnosed with meningioma annually in the U.S., and 97 out of every 100,000 people will be diagnosed with meningioma during their lifetime. Incidence increases with age, mostly in adults 65 and older, and the five-year relative survival rate is only 67%. Treatment for malignant meningiomas is generally attempted through surgery, although complete surgical removal can be difficult due to the infiltrative nature of these tumors. In addition, residual cells may contribute to recurrence. Radiation and chemotherapy are often considered to be adjuvant treatments to target any remaining tumor cells.
The Study Protocol
OBJECTIVES:
The primary objective of the NEO100-02 clinical study is to determine the six-month progression-free survival rate of the participants with secondary objectives being to examine the pharmacokinetics of NEO100 in the serum, the radiographic response by Response Assessment in Neuro-Oncology (RANO) criteria, to study any adverse events characterized by type, frequency, severity, as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v. 5.0), seriousness and relationship to study therapy NEO100, and to correlate changes from baseline in vital signs and clinical laboratory parameters (hematology and chemistry) as well as ECOG performance.
DESIGN:
The Phase 2 clinical trial is an open-label study to identify the safety, pharmacokinetics, and efficacy of a repeated dose regimen of intranasally delivered NEO100 (perillyl alcohol) for the treatment of patients with radiographically-confirmed residual, progressive, or recurrent high-grade meningioma. There will be up to 30 patients enrolled in the study to enroll 28 evaluable patients. NEO100 will be self-administered four times daily for a 28-day treatment cycle up to twelve treatment cycles until disease progression or death, whichever occurs first. After cycle twelve, patients will be given the option to continue receiving compassionate use treatment cycles.
Patients will be 12 years of age or older and have radiologically confirmed residual, progressive, or recurrent high-grade meningioma with an expected survival of at least three months. Patients must have measurable residual disease following at least minimally safe resection and radiation therapy, progressive disease or recurrent disease, must be on a stable or decreasing dose of steroids for at least five days before the date of the informed consent, and must have ECOG performance status of 0 –2 or KPS ≥ 60.
Sites selected for the study will be numbered using a two-digit system starting with 01. At each site, patients
will be numbered sequentially using a three-digit system starting with 101. For example, the second patient at the first site will be 01-102.
Each participant in the study will undergo a 12-cycle administration of NEO100 with each cycle lasting 28 days with four administrations of intranasal NEO100 every four hours. On day 1, cycle 1, the first treatment and P.K. sampling dose will be performed under close observation by adequately trained study personnel at the site. The trained study personnel should observe each patient closely for the duration of the drug administration to ensure the participant understands how to use the intranasal delivery mask, how to fit the mask properly, and how to inhale the formulation for maximum effect during the nebulized delivery. After the first administration, the participant will be given a NEO100 administration package with supplies sufficient for four daily doses during the 28-day cycle (+ up to 7 days). In addition, they will also be given a diary to record daily nasal delivery time, duration of the study drug administration, drug dosage, missed doses, and any adverse effects.
All patients must remain at least 75% compliant within a treatment cycle to remain in the study, for example, at least 84 of the 112 doses administered in a 28-day treatment cycle.
Patients will be followed every four weeks with a clinic visit that will look at the patient’s:
- Physical exam including:
- General Appearance
- Skin
- HEENT
- Chest
- Cardiovascular
- Abdomen
- Lymph nodes
- Extremities/back
- Musculoskeletal
- Neurological
- Review of concomitant medications and procedures
- Vital signs, including:
- Weight (pre-dose only)
- Pre-dose and post-dose in conjunction with PK study:
- Temperature
- Heart rate
- Respiratory rate
- Blood pressure
- Performance status: ECOG and KPS
- Safety evaluations: AEs and DLTs
- Hematology, including:
- Hemoglobin
- Hematocrit
- RBC count
- WBC count
- ANC
- Lymphocytes
- Monocytes
- Eosinophils
- Basophils
- Reticulocytes
- Platelet counts
- PT
- PTT
- INR
- Urinalysis, including protein, glucose, ketones, blood, specific gravity, bilirubin, and pH, as well as microscopic urinalysis (RBC, WBC, epithelial cells, bacteria).
- Serum chemistry: comprehensive metabolic panel (CMP) to include: albumin, alkaline phosphatase, ALT/SGPT, AST/SGOT, BUN, creatinine, electrolytes (sodium, potassium, calcium, chloride, bicarbonate, magnesium, phosphorous), glucose, and total bilirubin.
- Serum pregnancy test (for females of child-bearing potential
At the end of Cycles 2, 4 and 6 (Day 28 +7 days) these tests will be expanded to include any applicable USV such as a MRI of the brain with gadolinium and tumor assessment by Central Reader.
END of STUDY:
The End of Study/Early Discontinuation will occur after Cycle 12 or when disease progression is determined or consent is withdrawn, whichever occurs first. During this visit, patients who have completed Cycle 6 can confirm their consent to receiving further compassionate use treatment cycles under the standard of care by the investigator. The final in-office exam will consist of the examination and tests listed above. After the last dose of study medication, patients will be followed for PFS-6, PFS, and OS with visits or phone calls every three months until death or the start of another anti-cancer therapy and until the study analysis is performed, which will be after all patients have reached the six-month time point from their first dose.
Study Assessment:
After each patient’s participation in the study has been completed, an assessment of the treatment will be compiled and analyzed to form the basis for the clinical trial’s impact conclusions. The assessment will focus on determining the tumor response/progression, the progression of the disease, and the patient safety impact.
For analysis of tumor response and progression to the NEO100 treatment, the NeOnc clinical trial team will work in concert with the site sponsor to examine post-treatment MRI scans compared to the screening MRI scan, and tumor response will be assessed using the RANO response criteria for high-grade meningioma, which considers radiologic imaging, neurological status, and steroid dosing. For the MRI component of endpoint and efficacy analysis, the central MRI reports will be used. The final assessment of tumor response/progression will be made by the study site investigator in consultation with the sponsor with the following RANO criteria:
- Complete response (CR) requires all of the following:
- Complete disappearance of all enhancing measurable and nonmeasurable
disease sustained for at least eight weeks; - No new lesions;
- Stable or improved non-enhancing (T2/FLAIR) lesions;
- Patients must be off corticosteroids (or on physiologic replacement doses only);
- The patient is stable or has improved clinically.
- Complete disappearance of all enhancing measurable and nonmeasurable
- Partial response (PR) requires all of the following:
- A 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least eight weeks;
- No progression of non-measurable disease;
- No new lesions;
- Stable or improved non-enhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan;
- The corticosteroid dose at the time of the scan evaluation should be no greater than the dose at the time of the baseline scan;
- The patient is stable or has improved clinically.
- Stable disease (SD) requires all of the following:
- Does not qualify for complete response, partial response, or progression;
- Stable non-enhancing (T2/FLAIR) lesions on the same or lower dose of corticosteroids compared with baseline scan. If the corticosteroid dose was increased for new symptoms and signs without confirmation of disease progression on neuroimaging, and subsequent follow-up imaging shows that this increase in corticosteroids was required because of disease progression, the last scan considered to show stable disease will be the scan obtained when the corticosteroid dose was equivalent to the baseline dose.
Conclusion:
NeOnc anticipates that the data from the study will show that intranasal-delivery NEO100 will benefit meningioma tumor progression as good as or better than the results seen in its NEO100-01 trial on GBM. If the study results indicate a positive impact, NeOnc will submit its findings to the FDA for approval of a Phase 3 clinical trial. The study results will be published upon completion in a nationally recognized peer-reviewed publication.