OLIG2 Inhibitor CT-179 for Recurrent and Newly-diagnosed Glioblastoma
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: CT-179.
- Who it may be relevant to
- Registry conditions: Recurrent Glioblastoma, Newly Diagnosed MGMT Unmethylated Glioblastoma. Basic parameters: 18 years — 75 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Australia
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
A Phase 1, Two-Part, Accelerated Dose Titration Trial of CT-179 as Monotherapy in the Treatment of Recurrent Glioblastoma and in Combination With Radiation Therapy in the Treatment of Newly Diagnosed MGMT-Unmethylated Glioblastoma
Overview
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.
Detailed description
The OPAL trial is a Phase 1, multi-center, open-label study designed to evaluate the safety and tolerability of CT-179. CT-179 is an orally administered small molecule that modulates the oligodendrocyte transcription factor 2 (OLIG2). The study will enroll up to 54 adult patients with isocitrate dehydrogenase (IDH)-wild type Glioblastoma (GBM).
To evaluate the drug across different stages of the disease, the trial is structured into distinct treatment groups:
* Treatment Arm 1 (Recurrent GBM): In Treatment Arm 1, patients will receive a daily oral dose of CT-179 for a 28-day Dose-Limiting Toxicity (DLT) assessment period. Dose escalation begins at 0.65 mg/kg and may proceed up to 10.4 mg/kg across six planned cohorts. The first three cohorts will use an Accelerated Titration design (one patient per cohort) before reverting to a standard 3+3 dose-escalation design if specific moderate or dose-limiting toxicities are observed. * Treatment Arm 2 (Newly Diagnosed MGMT-Unmethylated GBM):
Enrollment in Arm 2 will only begin after the sixth cohort in Arm 1 successfully clears its 28-day DLT period. These patients will receive CT-179 for a one-week lead-in, followed by six weeks of CT-179 administered concurrently with standard radiation therapy (60 Gy). The DLT observation period for this arm lasts up to 12 weeks and uses a standard 3+3 dose-escalation design.
* Intra-Tumoral Drug Concentration (IDC) Sub-Study: Once the Maximum Tolerated Dose (MTD) is established in Arm 1, a sub-study will evaluate how well CT-179 penetrates tumor tissue. Patients will receive CT-179 for 7 to 14 days before their scheduled tumor resection so that intra-tumoral drug concentrations can be measured from the resected tissue. * Study Objectives: The primary objective across all cohorts is to determine the MTD and the Recommended Phase 2 Dose (RP2D) for CT-179. Secondary and exploratory measures include tracking pharmacokinetics (PK), assessing preliminary efficacy via Overall Response Rate (ORR) and Progression-Free Survival (PFS) using RANO 2.0 criteria, and evaluating changes in tumor metabolism via FET-PET imaging.
Interventions
- Drug CT-179
Daily administration of CT-179
Primary outcome measures
- Determine Maximum Tolerated Dose (MTD) in TA1 in patients with rGBM [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 [Time frame: From first dose of CT-179 through 4 weeks after completion of radiotherapy (up to 12 weeks).]
Secondary outcome measures (7)
- Incidence of Adverse Events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 [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 frame: From first dose of CT-179 through the end of treatment, assessed for up to 24 months.]
- Overall response rate (ORR) [Time frame: From first dose of CT-179 until documented disease progression or withdrawal, assessed for up to 24 months.]
- Progression-Free Survival (PFS) [Time frame: From first dose of CT-179 to first documented disease progression, assessed for up to 24 months.]
- Pharmacokinetic parameters Cmax [Time frame: From first dose of CT-179 through the end of treatment, assessed for up to 24 months.]
- Pharmacokinetic parameters T1/2 [Time frame: From first dose of CT-179 through the end of treatment, assessed for up to 24 months.]
- Pharmacokinetic parameters AUC [Time frame: From first dose of CT-179 through the end of treatment, assessed for up to 24 months.]
Eligibility criteria
Inclusion criteria
- 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
- Contraception during study participation, as applicable
- Able to swallow tablets
Exclusion criteria
- 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
- Significant concomitant disorder or serious intercurrent illness
- History of prior malignancy, except adequately treated non-melanoma skin cancer, carcinoma in-situ of the cervix, or disease-free for more than 5 years
- Treatment for HIV, hepatitis B, or hepatitis C
- Any gastrointestinal disorder that could result in reduced absorption of CT-179
- Any psychiatric illness or social situation that would limit compliance with study requirements
- Dose of dexamethasone higher than 4 mg/day within 1 week of the first dose of study medication
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Non-randomized
- Model
- Sequential
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Australia · 2 centers
- Royal Brisbane and Women's Hospital — Herston
- Austin Health — Heidelberg
Identifiers
NCT: NCT07739017 · CT-179-102