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

NCT02704858 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: NEO100-01
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 12

Brief 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. 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 for Phase 2a. There will be up to 24 patients enrolled in Phase 1. There will be 25 patients enrolled in Phase 2a. For both phases of the study, NEO100 will be self-administered four times daily for a 28-day treatment cycles until disease progression, death or patient withdraw from study for any reason, whichever occurs first. Version 10 of the protocol changed the inclusion criteria for Phase 2a to limit inclusion to those patients with progressive or recurrent primary or secondary Grade IV gliomas expressing IDH1 mutations. Prior to the protocol amendment, 4 patients were enrolled who were IDH1 wild-type. Therefore, an additional 28 patients will be recruited for a total of 32 patients enrolled into Phase 2a of this study to have 35 evaluable cases. Version 12 of the protocol expanded the inclusion criteria for Phase 2a to include those patients with progressive or recurrent Grade III Astrocytoma expressing IDH1 mutations. Review of the literature specific to these patients found the same expected time to progression and death. As a result, the number of patients to enroll remains 32 to have 35 evaluable cases.

Conditions

Glioblastoma Multiforme

Keywords

recurrent glioblastoma; recurrent GBM

Outcome Measures

Primary Outcomes (3)

• Phase 1 Primary Outcome: Number of Participants with Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment

  Up to 6 months

• Phase 2 Primary Outcome: Number of Participants Who Are Alive Each Month For 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

  6 months

Study Arms (2)

NEO100 Phase 1

EXPERIMENTAL

Intranasal delivery of NEO100 (perillyl alcohol) four times a day, escalation up to four different doses to determine maximum tolerated dose.

Drug: Perillyl alcohol

NEO100 Phase 2A

EXPERIMENTAL

Intranasal delivery of NEO100 (perillyl alcohol) four times a day. Treatment of total of 25 patients at maximum tolerated dose.

Drug: Perillyl alcohol

Interventions

Perillyl alcohol DRUG

Intranasal administration

Also known as: NEO100

NEO100 Phase 1; NEO100 Phase 2A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must have radiographically-confirmed progression of, or recurrent, primary or secondary Grade IV glioma, including infratentorial (brainstem, cerebellar) glioma (confirmed by biopsy) and subcortical glioma.
• Patient must 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.
• Patient must have failed previous radiation treatment or combined treatment with temozolomide and radiation.
• If progression of disease occurs within 90 days of conformal radiation, the progression/recurrence must be outside of the radiation field or proven by biopsy/resection.
• Patient must be ≥ 18 years of age.
• Patient must have an ECOG performance status of 0-2 or KPS ≥ 60 (the latter for Phase 1 only).
• Patient must have an expected survival of at least three months.
• Patient must have a baseline MRI with gadolinium within 14 days of first administration of study drug.
• Patient must be willing to provide blood samples for pharmacokinetic study.
• If patient suffers from seizures, (s)he must be controlled on a stable dose of anti- epileptics for 14 days prior to the date of informed consent.
• Patient must have adequate organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Total bilirubin within normal institutional limits

You may not qualify if:

• If the patient meets any of the following criteria, the patient must not be enrolled:
• The size of the tumor is \> 30mm (length x width), as assessed at the baseline (pre- study) MRI evaluation.
• The tumor is multi-focal, as assessed at the baseline (pre-study) MRI evaluation.
• Patient has completed chemo-radiation within the last 90 days prior to first administration of study drug, 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 any form of anti-cancer therapy or treatment 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 anti-cancer therapy or treatment except temozolomide.
• Patient has had more than one recurrence or progression of his/her tumors.
• Patient has received any other investigational agents within 28 days prior to the first administration of study drug.
• Patient has had prior treatment with perillyl alcohol, administered either intravenously or intranasally.
• Patient has a history of allergic reactions attributed to perillyl alcohol.
• Patient has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patient must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Patient has a history of new diagnosis or treatment of cancer other than malignant glioma within five years prior to the date of informed consent, except for basal cell carcinoma or squamous cell carcinoma of the skin.

Sponsors & Collaborators

• Neonc Technologies, Inc.: lead

Study Sites (12)

University of Southern California

Los Angeles, California, 90033, United States

RECRUITING

Saint John Cancer Institute

Santa Monica, California, 90404, United States

RECRUITING

Georgia Cancer Center (Augusta University)

Augusta, Georgia, 30912, United States

RECRUITING

Ochsner Health

New Orleans, Louisiana, 70121, United States

RECRUITING

Atlantic Health (Overlook Medical Center)

Summit, New Jersey, 07901, United States

RECRUITING

Northwell Health

New York, New York, 10016, United States

RECRUITING

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44333, United States

RECRUITING

Baylor Scott & White Health

Dallas, Texas, 75061, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75235, United States

RECRUITING

University of Washington Medical Center

Seattle, Washington, 98105, United States

NOT YET RECRUITING

University of Wisconsin Hospital and Clinic

Madison, Wisconsin, 53792, United States

NOT YET RECRUITING

Related Publications (1)

• Schonthal AH, Peereboom DM, Wagle N, Lai R, Mathew AJ, Hurth KM, Simmon VF, Howard SP, Taylor LP, Chow F, da Fonseca CO, Chen TC. Phase I trial of intranasal NEO100, highly purified perillyl alcohol, in adult patients with recurrent glioblastoma. Neurooncol Adv. 2021 Feb 12;3(1):vdab005. doi: 10.1093/noajnl/vdab005. eCollection 2021 Jan-Dec.

  PMID: 33604574 RESULT

MeSH Terms

Conditions

Glioblastoma

Interventions

perillyl alcohol

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Thomas Chen, MD, PhD

  NeOnc Technologies Holdings, Inc.

  STUDY CHAIR

• Josh Neman, PhD

  NeOnc Technologies Holdings, Inc.

  STUDY DIRECTOR

Central Study Contacts

Christopher Beardmore

CONTACT

224-218-2408; chris@anovaevidence.com

Chloe Richmond

CONTACT

224 218 2408; chloe@anovaevidence.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2016
• First Posted: March 10, 2016
• Study Start: August 1, 2017
• Primary Completion: March 30, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: March 2, 2026

Record last verified: 2026-02

Locations

US (12)