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Astrocytoma, IDH-Mutant, Grade 2Phase 1NCT03528642

Telaglenastat With Radiation Therapy and Temozolomide in Treating Patients With IDH-Mutated Diffuse Astrocytoma or Anaplastic Astrocytoma

A Phase 1 study testing Questionnaire Administration, Radiation Therapy and Telaglenastat Hydrochloride in people with Astrocytoma, IDH-Mutant, Grade 2 and Astrocytoma, IDH-Mutant, Grade 3, run by National Cancer Institute (NCI) at 25 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This phase 1b trial studies the side effects and best dose of telaglenastat in combination with radiation therapy and temozolomide in treating patients with IDH-mutated diffuse or anaplastic astrocytoma. Telaglenastat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 16 years and older
What is being tested?
Questionnaire Administration, Radiation Therapy and Telaglenastat Hydrochloride
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
25 sitesUnited States
Study dates
1 May 2019to 18 Sep 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patients must have histopathologic or molecular confirmation of either IDH-mutant DA or IDH-mutant AA. Acceptable IDH mutations for study eligibility include any IDH1 mutation at codon 132 or any IDH2 mutation at codon 172.
  • Age >= 16 years. The intended neurocognitive tests have not been validated in children below the age of 16.
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%).
  • Hemoglobin > 9.0 g/dL (within 14 days prior to registration)
  • Leukocytes >= 3.0 x 10^9/L (within 14 days prior to registration)
  • Absolute neutrophil count >= 1.5 x 10^9/L (within 14 days prior to registration)
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  • Platelets >= 100 x 10^9/L (within 14 days prior to registration)
  • International normalized ratio (INR) =< 1.5 x upper limit of normal (ULN) (within 14 days prior to registration)
  • Partial thromboplastin time (PTT) or activated partial thromboplastin time (APTT) =< 1.5 x ULN (within 14 days prior to registration)
  • Patients on a stable dose of anti-coagulation therapy will be allowed to participate if they have no signs of bleeding or clotting and the INR/PT and PTT/aPTT results are compatible with an acceptable risk-benefit ratio as per the investigator's discretion.
  • Total bilirubin =< 1.5 x institutional ULN and < 3 mg/dL for patients with Gilbert's disease (within 14 days prior to registration)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) \& alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN (within 14 days prior to registration)
  • Creatinine =< 1.5 x institutional ULN or creatinine clearance >= 60 mL/minute
  • If there is history of human immunodeficiency virus (HIV) infection, patients must be on effective antiretroviral therapy and HIV viral load must be undetectable within 6 months of study enrollment.
  • If there is history of chronic hepatitis B virus (HBV) infection, patients must have either been treated or are on suppressive therapy (as indicated), and HBV viral load must be undetectable.
  • If there is history of hepatitis C virus (HCV) infection, patients must have been treated and HCV viral load must be undetectable.
  • Patient must have measurable disease by RANO criteria (dose expansion cohort only).
  • Patient must be at least 7 days beyond stereotactic biopsy and/or at least 14 days beyond open craniotomy at the time of registration.
  • Patients must have been on a stable or decreasing dose of corticosteroids over the last 7 days at the time of registration.
  • Patients must have been on a stable or decreasing dose of antiepileptic therapy over the last 14 days at the time of registration.
  • Females of childbearing potential must have a negative pregnancy test (=< 14 days) prior to start of trial treatment. The effects of telaglenastat (CB-839) HCl on the developing human fetus are unknown. For this reason and because alkylating agents as well as TMZ are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of telaglenastat (CB-839) HCl administration.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification. To be eligible for this trial, patients should be class 2B or better.
  • Availability of archival FFPE tumor tissue collected within 12 months prior to registration.

Who cannot join

  • Patients must not have received prior chemotherapy to treat the glioma.
  • Patients who are receiving any other investigational agents.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to telaglenastat (CB-839) HCl or TMZ.
  • Patient must not have received prior radiation therapy to the brain. Prior radiation therapy to the head and neck is also excluded if radiation fields overlap.
  • No prior use of Gliadel wafers.
  • Patient must have no evidence of either infratentorial or spinal involvement with tumor.
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  • Patients who are unable to swallow tablets.
  • Patients who are at risk for impaired absorption of oral medication including, but not limited to, refractory vomiting, gastric resection/bypass, and duodenal/jejunal resection.
  • Patients with uncontrolled intercurrent illness.
  • Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for more than 3 years.
  • Pregnant women are excluded from this study because telaglenastat (CB-839) HCl is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with telaglenastat (CB-839) HCl, breastfeeding should be discontinued if the mother is treated with telaglenastat (CB-839) HCl. These potential risks may also apply to TMZ.
  • Adolescent patients who require sedation for magnetic resonance imaging (MRI) or magnetic resonance spectroscopy (MRS).
  • Patients with psychiatric illness/social situations that would limit compliance with study requirements.
  • The primary language of communication for the patient must be English (dose expansion cohort only). The intended neurocognitive tests have not been validated in patients who do not primarily speak English.

Trial locations and contacts

25 sites in 1 country.

25 sites in 1 country

United States25 sites

  • University of Michigan Rogel Cancer Center

    Ann Arbor, Michigan, 48109

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona, 85054

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

  • Siteman Cancer Center at Christian Hospital

    St Louis, Missouri, 63136

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • Sibley Memorial Hospital

    Washington D.C., District of Columbia, 20016

Other trials in United States

About this study

Official title: A Phase 1b Trial of Telaglenastat (CB-839) HCI in Combination With Radiation Therapy and Temozolomide in Patients With IDH-Mutated Diffuse Astrocytoma and Anaplastic Astrocytoma

This phase 1b trial studies the side effects and best dose of telaglenastat in combination with radiation therapy and temozolomide in treating patients with IDH-mutated diffuse or anaplastic astrocytoma. Telaglenastat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Chemotherapy drugs, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving telaglenastat with radiation therapy and temozolomide may work better than surgery, radiation therapy, and temozolomide in treating patients with IDH-mutated diffuse astrocytoma or anaplastic astrocytoma.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Determine the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D) of telaglenastat (CB-839) hydrochloride (HCl) when combined with radiation therapy (RT) and temozolomide (TMZ) in patients with newly diagnosed IDH-mutated diffuse astrocytoma (DA) and anaplastic astrocytoma (AA).

SECONDARY OBJECTIVES:

  1. To observe and record anti-tumor activity. II. Determine the safety and tolerability of RT/TMZ/telaglenastat (CB-839) HCl in patients based on physician reported adverse event (AE) data.

III. Estimate the 2-year progression-free survival (PFS2) of RT/TMZ/telaglenastat (CB-839) HCl in patients with IDH-mutated glioma based on the Response Assessment in Neuro-Oncology (RANO) criteria.

IV. Estimate the 2-year overall survival (OS2) of RT/TMZ/telaglenastat (CB-839) HCl in patients with IDH-mutated glioma based on RANO criteria.

CORRELATIVE OBJECTIVES:

  1. Determine the minor response rate (MRR) and clinical benefit rate (CBR) for the combination of telaglenastat (CB-839) HCl and RT/TMZ in IDH-mutated glioma based on RANO criteria.

II. Determine the patient-reported tolerability of RT/TMZ/telaglenastat (CB-839) HCl using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) instrument to measure self-reported symptom severity and interference with daily activities.

II. Determine the neurocognitive impact of telaglenastat (CB-839) HCl when used in combination with RT/TMZ.

III. Determine the effect of telaglenastat (CB-839) HCl/RT/TMZ on plasma oncometabolite levels of glutamine, glutamate, aspartate, asparagine, and 2-hydroxyglutarate (2-HG) in patients with IDH-mutated glioma and associate the changes with disease response.

IV. Determine the effect of telaglenastat (CB-839) HCl/RT/TMZ on tumor glutamine and glutamate MRS signals in patients with IDH-mutated glioma and associate the signal with disease response.

  1. Determine the pharmacokinetics (PK) of telaglenastat (CB-839) HCl when used alone and in combination with TMZ.

VI. To perform molecular profiling assays on archived tumor tissue and peripheral blood, including, but not limited to, low-pass whole genome sequencing (WGS), whole exome sequencing (WES), and messenger ribonucleic acid (RNA) sequencing (RNA-Seq) in order to VIa. Identify potential predictive and prognostic biomarkers beyond any genomic alteration by which treatment may be assigned.

VIb. Identify resistance mechanisms using genomic deoxyribonucleic acid (DNA)- and RNA-based assessment platforms.

VII. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research; specimens will be annotated with key clinical data, including presentation, diagnosis, staging, summary treatment, and if possible, outcome.

VIII. To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood (for cell-free DNA analysis), and nucleic acids obtained from patients at the Experimental Therapeutics Clinical Trials Network (ETCTN) Biorepository at Nationwide Children's Hospital.

OUTLINE: This is a dose escalation study of telaglenastat.

Patients receive telaglenastat orally (PO) twice daily (BID) 7 days a week, temozolomide PO once daily (QD) 7 days a week, and undergo RT 5 days a week for up to 5.5 weeks (diffuse astrocytoma) or 6.5 weeks (anaplastic astrocytoma) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 2 years.

Being tested
Questionnaire Administration, Radiation Therapy, Telaglenastat Hydrochloride, Temozolomide
Medical subject headings
Astrocytoma, Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Questionnaire AdministrationOther

    Ancillary studies

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate

    Undergo RT

  • Telaglenastat HydrochlorideDrug

    Also called CB-839 HCl, Glutaminase Inhibitor CB-839 Hydrochloride

    Given PO

  • TemozolomideDrug

    Also called CCRG-81045, Gliotem, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831

    Given PO

Study groups in NCT03528642
Study groupRoleWhat they receive
Treatment (telaglenastat, temozolomide, RT)ExperimentalPatients receive telaglenastat PO BID 7 days a week, temozolomide PO QD 7 days a week, and undergo RT 5 days a week for up to 5.5 weeks (diffuse astrocytoma) or 6.5 weeks (anaplastic astrocytoma) in the absence of disease progression or unacceptable toxicity.
Receives: Other: Questionnaire Administration; Radiation: Radiation Therapy; Drug: Telaglenastat Hydrochloride; Drug: Temozolomide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D)

    MTD is defined as the dose level below the lowest dose that induces dose limiting toxicity (DLT) in at least 2 patients (out of 6). A total of 6 patients must be treated at the MTD. It is possible that the MTD will be unknown after this study (e.g., if the highest tested dose has fewer than 2 patients with DLT, out of 6). In this case, the highest dose is defined as the RP2D. A 3 + 3 cohort expansion design to determine toxicity-based dose escalation of telaglenastat (CB-839) hydrochloride (HCl) and external beam fractionated radiation therapy (RT) with concurrent temozolomide (TMZ) among patients with IDH-mutated diffuse astrocytoma (DA) or anaplastic astrocytoma (AA).

    Measured: Up to 6.5 weeks

Secondary outcomes (10)

  1. Objective response rate (ORR) as defined by Response Assessment in Neuro-Oncology (RANO) criteria

    ORR is defined as the rate of either complete response (CR), partial response (PR), or minor response (MR) by RANO criteria for low-grade gliomas at 6 months after initiation of RT/TMZ/telaglenastat (CB-839) HCl therapy. The ORR will be estimated using properties of the binomial distribution. 95% exact confidence intervals will also be calculated.

    Measured: Up to 6 months from the start of study treatment

  2. Clinical benefit rate (CBR) as defined by RANO criteria

    CBR is defined as the rate of either CR, PR, MR, or stable disease (SD) by RANO criteria for low-grade gliomas at 6 months after initiation of RT/TMZ/telaglenastat (CB-839) HCl therapy. The CBR will be estimated using properties of the binomial distribution. 95% exact confidence intervals will also be calculated.

    Measured: Up to 6 months from the start of study treatment

  3. Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE)

    The safety and tolerability of RT/TMZ/telaglenastat (CB-839) HCl in patients is based on physician reported adverse event (AE) data.

    Measured: Up to 2 years

  4. Progression-free survival (PFS2) as defined by response assessment in neuro-oncology (RANO) criteria

    PFS2 rate will be estimated using properties of the binomial distribution. 95% exact confidence intervals will also be calculated.

    Measured: Up to 2 years

  5. Overall survival (OS2) as defined by RANO criteria

    OS2 rate will be estimated using properties of the binomial distribution. 95% exact confidence intervals will also be calculated.

    Measured: Up to 2 years

  6. Assessment of pharmacokinetic (PK) parameters

    The PK of telaglenastat (CB-839) HCl will also be summarized using descriptive statistics and will be compared to historical data. Measurement of plasma concentrations of telaglenastat (CB-839) HCl and its metabolites (if authentic standards are available) will be performed using validated liquid chromatography-tandem mass spectrometry (LC/MS/MS) assays. The plasma concentration-time data will be analyzed by standard noncompartmental analysis using the program Phoenix WinNonlin 6.4 to determine apparent total clearance of the drug from plasma after oral administration (Cl/F), area under the plasma concentration-time curve from time zero to time t (AUCt), area under the plasma concentration-time curve from time zero to infinity, Cmax, time to reach maximum plasma concentration following drug administration (Tmax), t1/2, and accumulation.

    Measured: Pre-dose, 0.5, 1, 2, 4, and 8 hours post-dose on days -7, 1, and 15

  7. Assessment of self-reported symptoms as measured by MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) instrument

    MDASI-BT instrument is used to measure self-reported symptom severity and interference with daily activities. The study will use descriptive statistics to describe how patients rate symptom severity and interference with function at each time point. Compliance rates will be calculated as the number of received valid forms over the number of expected forms. Differences between groups in compliance will be tested by use of Fisher's exact test at every time point.

    Measured: Up to 2 years

  8. Assessment of neurocognitive impact

    For each test in the battery, a standard error of measurement will be used to derive the Reliable Change Index (RCI) which will be used to represent the 90% confidence interval for the difference in raw scores from baseline to follow-up assessment will be coded as 1 (deterioration), 2 (no change), and 3 (improved) according to the RCI. Percentage of patients in each dose cohort who show meaningful losses or gains in the various tests or test domains over the course of the study will be provided by frequency tables. Dose cohort differences will be compared using chi-squared analysis. Time-to-progressions will be estimated by Kaplan-Meier method and analyzed by Cox regression model adjusting all stratification factors.

    Measured: Baseline up to 2 years

  9. Assessment of plasma oncometabolites

    Plasma oncometabolites (asparagine, aspartate, glutamine, glutamate, and 2-HG) will be compared using changes in values after treatment with the patient's individual baseline values using either the paired t-test or the Mann-Whitney nonparametric U-test as needed. A significant change is defined as a 10% change from baseline.

    Measured: Baseline up to day 71

  10. Assessment of tumor oncometabolites as measured by magnetic resonance spectroscopy (MRS)

    Tumor oncometabolites (2-HG, glutamine, and glutamate, as measured by MRS) will be compared using changes in values after treatment with the patient's individual baseline values using either the paired t-test or the Mann-Whitney nonparametric U-test as needed. A significant change is defined as a 10% change from baseline.

    Measured: Baseline up to day 45

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 May 2018
  2. Study start1 May 2019
  3. Primary completion10 Dec 2024
  4. Study completion18 Sep 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03528642
Sponsor's protocol ID
NCI-2018-00876
Other IDs
NCI-2018-00876, 10218, 10218, UM1CA186686, UM1CA186709
Status last verified
Sep 2026
First submitted
17 May 2018
Last updated
22 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Questionnaire Administration, Radiation Therapy and Telaglenastat Hydrochloride in people with Astrocytoma, IDH-Mutant, Grade 2 and Astrocytoma, IDH-Mutant, Grade 3, run by National Cancer Institute (NCI) at 25 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 22 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) (time frame: Up to 6.5 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03528642.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2026.

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