Phase I/II Study of Zotiraciclib for Recurrent Gliomas with IDH1 or IDH2 Mutations
This study is testing zotiraciclib, a drug that works by blocking certain signals (a kinase inhibitor), for people with recurrent diffuse gliomas. These are brain tumors that have come back and have specific genetic changes called IDH1 or IDH2 mutations. The study aims to find the best dose of zotiraciclib and see if it can help people live longer without their tumor growing (progression-free survival) compared to existing information. You may be able to join if you are 15 or older, have a diffuse glioma that has returned, and your tumor has IDH1 or IDH2 mutations. The study is currently unclear on its recruitment status and plans to enroll 96 participants.
- Study design
- This is a Phase I/II interventional study. It will determine the recommended dose and then assess how well zotiraciclib works.
- What's involved
- You will take zotiraciclib by mouth on specific days over 28-day cycles for up to 18 cycles. You will have physical exams, blood and urine tests, heart function tests, and brain MRIs. A new biopsy might be needed.
- Compensation
- Not stated in the trial record.
- Follow-up
- The study will measure progression-free survival at 12 months after treatment.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT05588141
A Phase I/II Study of Zotiraciclib for Recurrent Malignant Gliomas With Isocitrate Dehydrogenase 1 or 2 (IDH1 or IDH2) Mutations
Recruiting
PHASE1Ages 15+InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~96 participants
Updated 2026-08-28 on ClinicalTrials.gov
What's tested:Zotiraciclib
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
To determine 12 months PFS in participants w/ recurrent glioma, IDH1/2-mutant, WHO grade 3 treated w/ zotiraciclib in comparison w/ the established brain tumor database matched for tumor molecular characteristics and clinical prognostic factors
Measured over 12 Months
+1 more outcome measured
Conditions
Where it's being run
1 sites across 1 statesMaryland1
Study leadership
- Jing Wu, M.D. · PRINCIPAL_INVESTIGATOR · National Cancer Institute (NCI)
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Participants must have diffuse glioma, WHO grades 2-4, histologically confirmed by Laboratory of Pathology, NCI.
IDH1 or IDH2 mutation status confirmed by TruSight(TM) Oncology 500 performed in LP, NCI or prior documentation of IDH1 or IDH2 mutation status
Participants must have received prior treatment (e.g., radiation, conventional chemotherapy, or vorasidenib) prior to disease progression.
Participants must have recurrent disease, proven histologically or by imaging studies
Participants who have undergone prior surgical resection are eligible for enrollment to cohorts 1-4.
Age \>15 years
Karnofsky \>70%
Participants must have adequate organ and marrow function as defined below:
leukocytes \>=3,000/microliter
absolute neutrophil count (ANC) \>=1,500/microliter
platelets \>100,000/microliter
total bilirubin \<=2x ULN (ULN 1.3 mg/dl) except for participants with Gilbert Syndrome
AST \< 3x ULN (ULN 34U/L)
ALT \< 3x ULN (ULN 55U/L)
serum creatinine \< 1.5 mg/dL
calculated creatinine clearance by CKD-EPI equation \> 60 cc/min
Participants must have recovered from the adverse effects of prior therapy to grade 2 or less (per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0)
Individuals of child-bearing potential (IOCBP) and men must agree to use highly effective contraception (hormonal, intrauterine device (IUD), abstinence, tube ligation, partner has had a previous vasectomy) at the study entry, for the duration of study treatment, and up to 3 months after the last dose of zotiraciclib
Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 3 months after study treatment discontinuation
Participants must be scheduled for brain tumor biopsy or surgical resection at NIH (Cohort 5 only)
The ability of a participant, parent or legal guardian of minor participant to understand and the willingness to sign a written informed consent document. No Legally Authorized Representative can provide initial consent.
Exclusion
More than one disease relapse in those with initial diagnosis of WHO grade 3-4, or more than two disease relapses in those with initial diagnosis of WHO grade 2 for Phase II. For Phase I enrollment, there are no limits on the number of prior recurrences.
Prior therapy with:
any investigational agent (including IDH mutant inhibitor) and/or standard of care cytotoxic therapy within 28 days prior to treatment initiation
vincristine within 14 days prior to treatment initiation
nitrosoureas within 42 days prior to treatment initiation
procarbazine within 21 days prior to treatment initiation
non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, within 7 days prior to treatment initiation
surgery within 14 days prior to treatment initiation
radiation therapy within 30 days prior to treatment initiation
bevacizumab for tumor treatment. Note: participants who received bevacizumab for symptom management, including but not limited to cerebral edema, or pseudo progression can be enrolled
Prolonged QTc \>470ms as calculated by correction formula on screening electrocardiogram (ECG) (QTCf can be used; QTCb can be used for participants with sinus bradycardia)
Prior invasive malignancies within the past 3 years prior to study treatment initiation (with the exception of non-melanoma skin cancers, carcinoma in situ of the cervix, melanoma in situ, or any localized cancer for whom the systemic standard of care therapy is not required)
History of allergic reactions attributed to compounds of similar chemical composition to zotiraciclib, such as flavopiridol
Pregnancy (confirmed with beta-HCG serum or urine pregnancy test performed at screening)
Uncontrolled intercurrent illness or social situations that would limit compliance with study requirements
Uncontrolled primary diabetes mellitus
What this trial measures
- To determine 12 months PFS in participants w/ recurrent glioma, IDH1/2-mutant, WHO grade 3 treated w/ zotiraciclib in comparison w/ the established brain tumor database matched for tumor molecular characteristics and clinical prognostic factors12 Months
Proportion of patients that have progressive disease after 12 months
- To estimate recommended phase II dose (RP2D) of zotiraciclib28 days
Number of DLTs within the DLT Period