OLIG2 Inhibitor CT-179 for Recurrent and Newly-diagnosed Glioblastoma

ConditionsRecurrent Glioblastoma Newly Diagnosed MGMT Unmethylated Glioblastoma

Trial statusNot yet recruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

Age18-75

SponsorOlivia Newton-John Cancer Research Institute

About this trial

This is a first-in-human Phase 1 two-part, open-label, multi-center, dose escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and maximum tolerated dose (MTD) of CT-179 in patients with recurrent glioblastoma and newly diagnosed MGMT-unmethylated glioblastoma who are eligible to receive radiation therapy following surgery, and to establish the recommended Phase 2 dose.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Male or female aged ≥ 18 years at the time of signing informed consent

Supratentorial, histologically confirmed diagnosis of primary GBM that meets the current diagnostic classification: 2021 WHO Classification of Tumors of the Central Nervous System

KPS score ≥ 70

Adequate organ function

Disqualifiers

Treatment with an investigational agent within the last 30 days excluding 5- aminolevulinic acid (5-ALA)

Placement of Gliadel wafers or similar local therapy at time of surgery

Receive bevacizumab

Evidence of intracranial or intra-tumoral hemorrhage

Trial design

Design model

Sequential

Treatments tested in this trial

CT-179
Drug
Daily administration of CT-179

Treatment groups

54 Participants

are divided into 2 treatment groups

Group A: Treatment Arm 1 (TA1) (recurrent GBM)Experimental treatment 1 intervention

Group B: Treatment Arm 2 (TA2) (newly diagnosed MGMT-unmethylated GBM)Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

Determine Maximum Tolerated Dose (MTD) in TA1 in patients with rGBM

The MTD will be the highest tested dose of CT-179 at which protocol specified number of patients experience a DLT or the MAD at the highest administered dose in the absence of a DLT.

Time frame

From first dose of CT-179 through the end of the 28-day DLT assessment period (Day 28) for each cohort.

Determine MTD/RP2D in TA2 in patients with newly diagnosed MGMT-unmethylated GBM

The MTD will be the highest dose of CT-179 at which protocol specified number of patients experience a DLT or the MAD at the highest administered dose in the absence of a DLT.

Time frame

From first dose of CT-179 through 4 weeks after completion of radiotherapy (up to 12 weeks).

Secondary outcomes

Incidence of Adverse Events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0

Rate of patients reporting adverse events or serious adverse events

Time frame

From first dose of CT-179 through 28 days after the last dose of study treatment, assessed for up to 24 months.

Pharmacokinetic parameters Tmax

Time to maximum concentration (Tmax)

Time frame

From first dose of CT-179 through the end of treatment, assessed for up to 24 months.

Overall response rate (ORR)

Per RANO 2.0 (Response Assessment in Neuro-Oncology)

Time frame

From first dose of CT-179 until documented disease progression or withdrawal, assessed for up to 24 months.

Progression-Free Survival (PFS)

Per RANO 2.0 (Response Assessment in Neuro-Oncology)

Time frame

From first dose of CT-179 to first documented disease progression, assessed for up to 24 months.

Other outcomes

Effects of CT-179 on tumour metabolism

By fluoroethyl-L-tyrosine-positron emission tomography (FET-PET)

Time frame

Baseline, Day 29 (±7 days), and Day 57 (±7 days).

Determine intra-tumoral drug concentrations

Subset of rGBM patients treated at MTD

Time frame

At the time of surgery following 7-14 days of CT-179 treatment.

Predictive biomarkers of efficacy

OLIG1 and/or OLIG2 tumor expression levels, mutational status of TERT, TP53, EGFR, EGFRvIII, and PTEN

Time frame

From baseline through disease progression or withdrawal, assessed for up to 24 months.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Olivia Newton-John Cancer Research Institute

Lead sponsor

Curtana Pharmaceuticals, Inc.

Collaborator

Source ClinicalTrials.gov

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