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

February 13, 2024 updated by: Neonc Technologies, Inc.

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

49

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90033
        • Recruiting
        • University of Southern California
        • Contact:
        • Principal Investigator:
          • Frances Chow, MD
    • Louisiana
    • New York
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
    • Ohio
      • Cleveland, Ohio, United States, 44333
        • Recruiting
        • Cleveland Clinic
        • Contact:
        • Principal Investigator:
          • David Peereboom, MD
    • Texas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NEO100 Phase 1
Intranasal delivery of NEO100 (perillyl alcohol) four times a day, escalation up to four different doses to determine maximum tolerated dose.
Drug: Perillyl alcohol
Intranasal administration
Other Names:
  • NEO100
Experimental: NEO100 Phase 2A
Intranasal delivery of NEO100 (perillyl alcohol) four times a day. Treatment of total of 25 patients at maximum tolerated dose.
Drug: Perillyl alcohol
Intranasal administration
Other Names:
  • NEO100

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Neonc Technologies, Inc.

Investigators

  • Study Chair: Tom Chen, MD, PhD, NeOnc Technologies
  • Study Director: Vincent F Simmon, PhD, NeOnc Technologies
  • Study Director: Patrick Walters, NeOnc Technologies

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 8, 2016

Primary Completion (Estimated)

June 1, 2024

Study Completion (Estimated)

December 1, 2024

Study Registration Dates

First Submitted

January 27, 2016

First Submitted That Met QC Criteria

March 5, 2016

First Posted (Estimated)

March 10, 2016

Study Record Updates

Last Update Posted (Actual)

February 15, 2024

Last Update Submitted That Met QC Criteria

February 13, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NEO100-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Glioblastoma Multiforme

Clinical Trials on Perillyl alcohol

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Taiwan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe