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Protocol Details

A Phase I/II Study of Zotiraciclib for Recurrent High-Grade Gliomas with Isocitrate Dehydrogenase 1 or 2 (IDH1 or IDH2) Mutations

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18 Years
Max Age: N/A

Referral Letter Required


Population Exclusion(s)

Pregnant Women;


Brain Tumor;
Idh Mutation;
Recurrent Disease

Recruitment Keyword(s)



Brain Tumor;

Investigational Drug(s)


Investigational Device(s)



Drug: Zotiraciclib

Supporting Site

National Cancer Institute


Diffuse gliomas are tumors that affect the brain and spinal cord. Gliomas that develop in people with certain gene mutations (IDH1 or IDH2) are especially aggressive. Better treatments are needed.


To see if a study drug (zotiraciclib) is effective in people with recurrent diffuse gliomas who have IDH1 or IDH2 mutations.


People aged 18 years and older with diffuse gliomas that returned after treatment. They must also have mutations in the IDH1 or IDH2 genes.


Participants will be screened. They will have a physical exam with blood and urine tests. They will have tests of their heart function. They will have an MRI of their brain. A new biopsy may be needed if previous results are not available.

Zotiraciclib is a capsule taken by mouth with a glass of water. Participants will take the drug at home on days 1, 4, 8, 11, 15, and 18 of a 28-day cycle. They may also be given medications to prevent side effects of the study drug. The schedule for taking the study drug may vary for participants who will undergo surgery.

Participants will be given a medication diary for each cycle. They will write down the date and time of each dose of the study drug.

Participants will visit the clinic about once a month. They will have a physical exam, blood tests, and tests to evaluate their heart function. An MRI of the brain will be repeated every 8 weeks.

Participants may remain in the study for up to 18 cycles (1.5 years).

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-Participants must have diffuse glioma, WHO grades 2-4, histologically confirmed by Laboratory of Pathology, NCI

-IDH1 or IDH2 mutation status confirmed by TSO500 performed in LP, NCI

-Participants must have received prior treatment (e.g., radiation, conventional chemotherapy) 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 >=18 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

-Women of child-bearing potential (WOCBP) and men must agree to use highly effective contraception (hormonal, intrauterine device (IUD), abstinence, tube ligation, partner has had the 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 to understand and the willingness to sign a written informed consent document. No Legally Authorized Representative can provide initial consent.


More than one prior disease relapse (WHO grade 3-4) or more than two prior disease relapses (WHO grade 2)

-Prior therapy with:

--any investigational agent 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 Fridericia s correction formula on screening electrocardiogram (ECG)

-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 <=-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

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Yuan Y, Hess KR, Hilsenbeck SG, Gilbert MR. Bayesian Optimal Interval Design: A Simple and Well-Performing Design for Phase I Oncology Trials. Clin Cancer Res. 2016 Sep 1;22(17):4291-301. doi: 10.1158/1078-0432.CCR-16-0592. Epub 2016 Jul 12. PMID: 27407096; PMCID: PMC5047439.

Miller JJ, Loebel F, Juratli TA, Tummala SS, Williams EA, Batchelor TT, Arrillaga-Romany I, Cahill DP. Accelerated progression of IDH mutant glioma after first recurrence. Neuro Oncol. 2019 May 6;21(5):669-677. doi: 10.1093/neuonc/noz016. PMID: 30668823; PMCID: PMC6502499.

Wu J, Yuan Y, Long Priel DA, Fink D, Peer CJ, Sissung TM, Su YT, Pang Y, Yu G, Butler MK, Mendoza TR, Vera E, Ahmad S, Bryla C, Lindsley M, Grajkowska E, Mentges K, Boris L, Antony R, Garren N, Siegel C, Lollo N, Cordova C, Aboud O, Theeler BJ, Burton EM, Penas-Prado M, Leeper H, Gonzales J, Armstrong TS, Calvo KR, Figg WD, Kuhns DB, Gallin JI, Gilbert MR. Phase I Study of Zotiraciclib in Combination with Temozolomide for Patients with Recurrent High-grade Astrocytomas. Clin Cancer Res. 2021 Jun 15;27(12):3298-3306. doi: 10.1158/1078-0432.CCR-20-4730. Epub 2021 Mar 30. PMID: 33785481; PMCID: PMC8197750.

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Principal Investigator

Referral Contact

For more information:

Jing Wu, M.D.
National Cancer Institute (NCI)
NIHBC 37 BG RM 1142A
(240) 760-6036

NCI NOB Referral Group
National Cancer Institute (NCI)

(866) 251-9686

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office

Clinical Trials Number:


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