Safety and Efficacy Study in Recurrent or Progressive Grade III or IV IDH1 Mutated Glioma

Glioblastoma Multiforme Clinical Trial

Official title:

An Open-Label, Phase 1/2A Dose Escalation Study of Safety and Efficacy of NEO100 in Recurrent or Progressive Grade III or Grade IV Gliomas With IDH1 Mutation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02704858
• Other study ID #: NEO100-01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 8, 2016
• Est. completion date: December 2024

Study information

• Verified date: February 2024
• Source: Neonc Technologies, Inc.
• Contact: Christopher Beardmore
• Phone: 224-218-2408
• Email: chris[@]anovaevidence.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This multi-site, Phase 1/2a clinical trial is an open label study to identify the safety, pharmacokinetics, and efficacy of a repeated dose regimen of NEO100 (perillyl alcohol) for the treatment of patients with radiographically-confirmed progression of Grade IV glioma or recurrent primary or secondary Grade IV glioma or patients with progressed or recurrent Grade III glioma. The study will have two phases, Phase 1 and Phase 2a. Phase 1 is a standard cohort dose escalation 3+3 design used to determine the maximum tolerated dose (MTD) for Phase 2a. Fifteen (15) patients were enrolled into the Phase I portion of the clinical trial. The MTD for NEO100 was not reached in humans. As a result the NEO100 dose for Cohort 4 (288 mg/dose - 1152 mg/day) was carried into the Phase 2a portion of the clinical trial. Four (4) patients were enrolled into this study prior to implementation of implementation of version 10 of the clinical trial restricting the Phase 2a population to patients with progressive or recurrent primary or secondary Grade IV gliomas expressing IDH1 mutations or progressive or recurrent primary or secondary Grade IV gliomas expressing IDH1 mutations. None of the four (4) patients expressed IDH1 mutations. There will be 28 patients with progressive or recurrent primary or secondary Grade IV gliomas expressing IDH1 mutations or progressive or recurrent primary or secondary Grade IV gliomas expressing IDH1 mutations enrolled in Phase 2a of the clinical trial. Prior to implementing v10 of this protocol, four (4) patients were enrolled. These patients met the inclusion/exclusion criteria for v9 of the protocol and had wild type IDH1 status. For both phases of the study, NEO100 will be self-administered four times daily for a 28-day treatment cycle up to six treatment cycles until disease progression or death, whichever occurs first. At the completion of cycle six, patients will be given the option to continue receiving compassionate use treatment cycles.

Description:

Perillyl alcohol has previously been tested in 15 clinical studies in > 600 subjects This includes 13 studies in 255 subjects using oral administration sponsored by the National Cancer Institute and two studies in > 350 subjects using intranasal administration in Brazil. NEO100 is a highly purified (>99%) form of perillyl alcohol. Studies in Brazil suggest improved survival for patients with recurrent glioblastoma. Doses of 96 mg qid, 144mg qid, 192mg qid, and 288 mg qid administered intranasally to patients with recurrent GBM for up to 6 months, disease progression or death. From 3 to 6 patients will be evaluated after first cycle (28 days) until MTD is reached. MRI with gadolinium will be at base line, and at the beginning of even cycles. A total of 25 patients will be treated at the MTD. PK studies will be conducted during Phase 1 at first dosing, and after first dose of 3rd cycle.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 49
• Est. completion date: December 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have radiographically-confirmed progression of, or recurrent, primary or secondary Grade IV glioma, including infratentorial (brainstem, cerebellar) glioma (confirmed by biopsy) and subcortical glioma.; or

• Have radiographically-confirmed progression of, recurrent, primary or secondary Grade III astrocytoma.

• All patients must be on a stable or decreasing dose of steroids for at least five days prior to the date of informed consent.

• Must have failed previous radiation treatment or combined treatment with temozolomide and radiation.

• If progression of disease occurs within three months of conformal radiation, it must be outside of the radiation field or proven by biopsy/resection.

• Must have an ECOG performance status of 0 - 2, or KPS = 60.

• Must have an expected survival of at least three months.

• Must be willing to provide blood samples for pharmacokinetic study

• Must have adequate organ and marrow function

• Female patients of child-bearing potential and male patients must agree to use adequate contraception

• Must have the ability to understand, and the willingness to sign, a written informed consent.

• Phase 2a: Patient must have a confirmed IDH1 mutation reverse transcription polymerase chain reaction (rtPCR) or immunohistochemistry (unless continuing into the Phase 2a portion of the study from the Phase I portion of the study).

Exclusion Criteria:

• The size of the tumor is multi-focal and > 30mm in size, as assessed at the baseline (pre-study) MRI evaluation.

• Patient has completed chemo-radiation within the last three months, unless new contrast enhancement is outside of radiation field, or there is tissue proven recurrence or progression.

• Patient has had surgery within seven days prior to the date of informed consent.

• Patient has had chemotherapy within 28 days prior to first administration of study drug.

• Patient has not recovered from adverse events due to chemotherapy, immunotherapy, or radiation therapy administered more than 28 days prior to first administration of study drug.

• Patient has had prior treatment with bevacizumab, a chemotherapy wafer implant (Gliadel), or any other FDA- approved chemotherapy except temozolomide.

• Patient has had more than one recurrence or progression of their tumors.

• Patient is receiving any other investigational agents.

• Patient has a history of allergic reactions attributed to perillyl alcohol.

• Patient has uncontrolled intercurrent illness

• Patient has a history of new diagnosis or treatment of cancer other than malignant glioma within five years prior to start of the study, except for basal cell carcinoma or squamous cell carcinoma.

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

Drug:
• Perillyl alcohol
Intranasal administration

Locations

Country	Name	City	State
United States	Cleveland Clinic	Cleveland	Ohio
United States	Baylor Scott & White Health	Dallas	Texas
United States	University of Southern California	Los Angeles	California
United States	Ochsner Health	New Orleans	Louisiana
United States	Northwell Health	New York	New York
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Neonc Technologies, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1 Primary Outcome: Number of Participants with Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment		Up to 6 months
Primary	Phase 2 Primary Outcome: Number of Participants Who Are Alive Each Month For 6 Months		Up to 6 months
Primary	Phase 2 Primary Outcome: Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related To Treatment		6 months