Phase 1 safety and dose-finding of GLIX1 for adults with recurrent or progressive high-grade glioma

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This open-label, multicenter Phase 1 dose-escalation and expansion trial gives adults with recurrent or progressive grade 3–4 glioma daily oral GLIX1 until disease progression or unacceptable toxicity. The dose-escalation phase will identify the optimal tolerable dose using safety, tolerability, pharmacokinetics, and preliminary clinical activity, followed by a dose-expansion cohort. GLIX1 is a small-molecule TET2 agonist that increases DNA oxidation at 5-methylcytosine, producing clustered single-strand breaks that can convert to lethal double-strand breaks in cancer cells. Enrollment requires predefined washout periods and recovery from prior treatment toxicities, with treatment continuing until progression or intolerable side effects.

Why it matters

Who can join: the full rules

Main Inclusion Criteria:

* Adult patients aged ≥18 years at the time of informed consent
* Participants must have histologically confirmed Grade 3 or Grade 4 glioma
* Recurrent or progressive disease
* A maximum of two prior treatment lines
* Interval of at least 3 months since the last day off of radiotherapy, unless tumor progression and index lesion is outside the prior radiation field.
* Interval since last dose of systemic therapy and Baseline MRI of ≥28 days, except:

  * for nitrosoureas (e.g., lomustine, carmustine, fotemustine): 42 days (6 weeks)
  * for monoclonal antibodies: 42 days (6 weeks)
  * for small molecules, 4 weeks or at least 5 half-lives (whatever is longer)
* Recovered from all toxicities from prior treatments to Grade 1 or less by NCI CTCAE v6.0:
* Participants receiving corticosteroids must be on a stable or decreasing dose of ≤6 mg daily dexamethasone (or ≤40 mg prednisone) for the 7 days prior to the start of study treatment.
* Participants with seizures must be adequately controlled on a stable regimen of anti-epileptic drugs.
* Adequate performance status: Eastern Cooperative Oncology Group (ECOG) 0 or 1.
* Ability to swallow tablets or capsules.
* Adequate hematological, liver and renal function.
* Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to first dosing. Women must use a highly effective form of contraception (with Pearl Index \<1%) for the duration of the study and for at least 3 months after the last dose of study medication.
* Men with partners of childbearing potential must be willing to use condoms in combination with a second effective method of contraception by the partner during the study and for at least 3 months after the last dose of study medication.

Main Exclusion Criteria:

* Known contraindication for gadolinium (Gd) based, contrast-enhanced MRI
* Prior history of another invasive malignancy unless a complete remission was achieved at least 3 years prior to enrolment AND no additional therapy is required during the study period, except for anti-estrogen or androgen therapy and/or bisphosphonates or denosumab.
* Participants with known active or uncontrolled infection, and/or unexplained fever \>38°C in the 3 days prior to the start of study treatment.
* Major non-tumor related surgical procedure or significant traumatic injury within 28 days prior to signing of consent.
* Receiving any investigational products (defined as treatment for which there is currently no regulatory authority-approved indication) within 4 weeks or 5 half-lives (whichever is the longest) prior to Baseline MRI.

Where it's running

• Stanford University
  Palo Alto, California, United States Recruiting
• Moffitt Cancer Center
  Tampa, Florida, United States Recruiting
• Northwestern Medicine
  Chicago, Illinois, United States Recruiting
• NYU Langone Health
  New York, New York, United States Recruiting

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.