Study of Niacin in Glioblastoma

October 13, 2023 updated by: AHS Cancer Control Alberta

A Phase I-II Study of Niacin in Patients With Newly Diagnosed Glioblastoma Receiving Concurrent Radiotherapy and Temozolomide Followed by Monthly Temozolomide

This is a single institution Phase I-II study to evaluate the tolerability and Maximum Tolerated Dose (MTD) (Phase I) and efficacy (Phase II) of adding Niacin CRT™ to standard first line treatment (concurrent Radiation Therapy (RT) and Temozolomide (TMZ) following by monthly TMZ - AKA Stupp protocol) in patients with newly diagnosed glioblastoma isocitrate dehydrogenase (IDH) wild type.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

During the Phase I stage Niacin CRT™ dose will be escalated every 4 weeks until the maximum tolerated dose (MTD) is determined. The MTD dose will be prescribed to patients during the Phase II stage.

During the Phase I study a sample of blood at baseline, at each level dose of Niacin CRT™, and every two months during the maintenance phase while on Niacin CRTTM will be sent to a lab to evaluate the peripheral activity of Niacin CRT™ in innate immune system cells. These samples will be taken at the time of routine standard of care lab work.

Based on prior clinical trials evaluating niacin extended release formulation for the management of dyslipidaemias there is vast experience on dose escalation of niacin. One of the main side effects is flushing that is ameliorated by escalating doses in intervals no shorter than 4 weeks and usually decreases with time.

Following this schema, there is no increase in dose coinciding with TMZ while administered in a 5/28 days schedule (given daily for 5 days of each 28-day cycle). This will not only improve tolerance but also will allow us to differentiate potential adverse events from chemotherapy from the ones from Niacin CRT™.

Study Type

Interventional

Enrollment (Estimated)

59

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

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 to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adults, 18 years old to 75 years old inclusive.
  • New diagnoses of glioblastoma IDH wild type.
  • ECOG 0-2 (Appendix I).
  • Candidates for concurrent standard first line treatment according to their Neuro-Oncologist and Radiotherapy Oncologist after maximal safe debulking neurosurgery. Patients that only had biopsy are included as long as pathology confirms the diagnoses and it is considered the maximal safe procedure for that patient.
  • Adequate hematological, renal and hepatic function (see details in Section 4.1 of the protocol).
  • Absence of known human immunodeficiency virus (HIV) infection, chronic hepatitis B or hepatitis C infection.
  • Absence of any other serious medical condition according to the medical judgment of the Qualified Investigator prior to registration.
  • Absence of any medical condition, which could interfere with oral medication intake.
  • Signed informed consent.
  • Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre.
  • Women/men of childbearing potential must have agreed to use a highly effective contraceptive method.

Exclusion Criteria:

  • Glioblastoma, IDH-mutant.
  • Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years. Additionally, any low grade or low risk malignancy not requiring treatment will not exclude a patient from participation in the trial.
  • Known hypersensitivity to niacin.
  • Inability to provide informed consent.
  • Active liver disease or unexplained persistent elevations of serum transaminases.
  • Active peptic ulcer or active gastrointestinal bleeding.
  • Unstable angina or myocardial infarction within 6 months.
  • Symptomatic gout.
  • Patients on 3-hydroxy-3-methylglutaryl-coenzyme (HMG-COA reductase) inhibitors that cannot discontinue them at least 2 weeks before starting Niacin CRT™.
  • Any prior systemic treatment for glioblastoma (standard, evidence based or experimental) or radiotherapy/radiosurgery.
  • Individuals with MRI non-compatible metal in the body, or unable to undergo MRI procedures including allergy to gadolinium.
  • Patients unfit for any treatment component, including contraindications for radiotherapy or Connective Tissue Disease.
  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
  • Has known psychiatric or substance abuse disorders that would interfere with compliance with the requirements of the trial.
  • Pregnant, breast-feeding, unable and/or unwilling to use contraception methods.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Niacin

Niacin controlled release technology (CRT):

Niacin CRT™ is to be started 7 days before concurrent Radiation Therapy (RT)- Temozolomide (TMZ) treatment.

Chemo/Radiation Therapy:

For all patients, regardless of the phase of the study, concurrent RT and TMZ for 6 weeks followed by 6-12 cycles of monthly TMZ will be given.

Concurrent Temozolomide:

TMZ will be administered from the first to the last day of RT at 75 mg/m2 orally (PO) for a maximum of 49 days.

Monthly Temozolomide:

Cycles of chemotherapy Day 1 to Day 5 every 28 days will start 28 days (+/- 2 days) after the end of RT-TMZ. First cycle of TMZ is administered at 150 mg/m2 Day 1-Day 5 by mouth (PO) and increased to 200 mg/m2 Day 1-Day 5 PO from cycle 2 onwards if well tolerated. While 6 cycles are standard of care, the Neuro-Oncologist may continue up to 12 cycles if clinically appropriate.
Drug: Niacin CRT
A controlled release technology (CRT) tablet of Niacin
Other Names:
  • Nicotinic acid
  • Vitamin B3

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determining the Maximum Tolerated Dose
Time Frame: Up to 24 weeks after registration onto the study
To evaluate and determine maximum tolerated dose (MTD) of Niacin CRT added to concurrent radiotherapy (RT) and temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GB).
Up to 24 weeks after registration onto the study
Evaluating if Niacin CRT Improves Glioblastoma Survival Rates
Time Frame: 6 months after determining the maximum tolerated dose which can last up to 24 weeks after registration onto the study
To evaluate if adding Niacin CRT to current standard first line treatment of GB improves progression free survival (PFS) at 6 months.
6 months after determining the maximum tolerated dose which can last up to 24 weeks after registration onto the study

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect of Niacin CRT in Peripheral Monocytes
Time Frame: From date of registration until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 5 years.
To evaluate the effect of Niacin CRT in peripheral monocytes by comparing control monocytoid cells to those that have been treated with Niacin.
From date of registration until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 5 years.
Response Rate Associated with Niacin
Time Frame: From date of registration until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 5 years.
To determine the response rate associated with the investigational regimen.
From date of registration until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 5 years.
Overall Survival Rate Associated with Niacin
Time Frame: From date of registration until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 5 years.
To determine the overall survival (OS) associated with the investigational regimen.
From date of registration until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 5 years.
Quality of Life While on Study using EORTC QLQ-C30 Questionnaires
Time Frame: From date of registration until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 5 years.
To determine Quality of Life (QOL) that will be evaluated throughout the study using EORTC QLQ-C30 questionnaires.
From date of registration until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 5 years.
Quality of Life While on Study using EORTC BN-20 Questionnaires
Time Frame: From date of registration until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 5 years.
To determine Quality of Life (QOL) that will be evaluated throughout the study using EORTC BN-20 questionnaires.
From date of registration until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 5 years.

Collaborators and Investigators

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

Sponsor

AHS Cancer Control Alberta

Collaborators

Tom Baker Cancer Centre

Investigators

  • Principal Investigator: Gloria Roldan Urgoiti, MD, Tom Baker Cancer Centre

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)

March 18, 2021

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

January 1, 2026

Study Registration Dates

First Submitted

December 3, 2020

First Submitted That Met QC Criteria

December 15, 2020

First Posted (Actual)

December 21, 2020

Study Record Updates

Last Update Posted (Actual)

October 16, 2023

Last Update Submitted That Met QC Criteria

October 13, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NiacinCNS2020

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

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.

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