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Advanced Malignant Solid NeoplasmPhase 2NCT03872427

Testing Whether Cancers With Specific Mutations Respond Better to Glutaminase Inhibitor, Telaglenastat Hydrochloride, Anti-Cancer Treatment, BeGIN Study

A Phase 2 study testing Biospecimen Collection, Computed Tomography and Magnetic Resonance Imaging in people with Advanced Malignant Solid Neoplasm and Metastatic Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 31 sites in United States.

Active, not recruiting

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

Official record
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Trial summary

This phase II trial studies how well glutaminase inhibitor telaglenastat hydrochloride (CB-839 HCl) works in treating patients with specific genetic mutations and solid tumors or malignant peripheral nerve sheath tumors that have spread to other places in the body (metastatic) or cannot be removed by surgery… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Computed Tomography and Magnetic Resonance Imaging
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
31 sitesUnited States
Study dates
14 Dec 2019to 16 Apr 2027
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically confirmed malignancy that is metastatic or unresectable
  • Patient must have histopathologic confirmation of advanced solid tumor with NF1 mutation, NF1 mutant MPNST, KEAP1/NRF2 mutant and STK11/LKB1 mutant tumors (molecular profiling performed in any Clinical Laboratory Improvement Act [CLIA] certified lab [including tumor and circulating cell-free (cf)DNA], e.g. Caris, FoundationOne, FoundationAct, Oncomine, Guardant etc.)
  • NOTE: For all cohorts annotation for actionability will be performed by the PRECISION ONCOLOGY DECISION SUPPORT (PODS) TEAM SHEIKH KHALIFA BIN ZAYED AL NAHYAN INSTITUTE FOR PERSONALIZED CANCER THERAPY (IPCT) THE UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER 6565 MD ANDERSON BLVD, HOUSTON, TX 77030
  • Patient must have no standard therapies available
  • Patient must be aged greater than 18 years old for all cohorts
  • Patients for NF1 mutant MPNST and NF1 mutant non-MPNST cohorts must be >= 40 kg
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  • Patient must be at least 4 weeks since any prior surgery or radiotherapy
  • Females of childbearing potential must have a negative serum pregnancy test (=< 14 days) prior to start of trial treatment
  • Response Evaluation Criteria in Solid Tumors (RECIST) measurable disease and biopsiable targetable lesion
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) by chest x-ray or as >= 10 mm (>= 1 cm) with CT scan, magnetic resonance imaging (MRI), or calipers by clinical exam
  • Patients with treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after central nervous system (CNS)-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,000/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) and up to 3 ml/dL for patients with Gilbert's disease
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN and =< 5 x institutional ULN for patients with liver metastases
  • Creatinine =< institutional ULN, as age appropriate OR
  • Glomerular filtration rate (GFR) >= 30 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • The effects of telaglenastat (CB-839) HCl on the developing human fetus are unknown. For this reason and because anti-metabolic agents like telaglenastat (CB-839) HCl 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

Who cannot join

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
  • Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1)
  • 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
  • Patients with glioma will be excluded
  • Patients with active or prior history of hepatitis B or C will be excluded
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  • Telaglenastat (CB-839) HCl is a weak in vitro inhibitor of CYP2C9. Therefore, patients receiving any medications or substances that are substrates of CYP2C9 are eligible, but should use caution with substrates that have a narrow therapeutic index. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because telaglenastat (CB-839) HCl is anti-metabolic agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events 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

Trial locations and contacts

31 sites in 1 country.

31 sites in 1 country

United States31 sites

  • UM Sylvester Comprehensive Cancer Center at Aventura

    Aventura, Florida, 33180

  • National Cancer Institute Developmental Therapeutics Clinic

    Bethesda, Maryland, 20892

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Northwestern University

    Chicago, Illinois, 60611

  • Wake Forest University at Clemmons

    Clemmons, North Carolina, 27012

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida, 33146

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

  • University of Kansas Clinical Research Center

    Fairway, Kansas, 66205

  • HaysMed

    Hays, Kansas, 67601

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • University Health Truman Medical Center

    Kansas City, Missouri, 64108

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • UM Sylvester Comprehensive Cancer Center at Kendall

    Miami, Florida, 33176

  • 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

  • The University of Kansas Cancer Center - Olathe

    Olathe, Kansas, 66061

  • Mercy Hospital Pittsburg

    Pittsburg, Kansas, 66762

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • UM Sylvester Comprehensive Cancer Center at Plantation

    Plantation, Florida, 33324

  • Salina Regional Health Center

    Salina, Kansas, 67401

  • Moffitt Cancer Center-International Plaza

    Tampa, Florida, 33607

  • Moffitt Cancer Center - McKinley Campus

    Tampa, Florida, 33612

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • University of Kansas Health System Saint Francis Campus

    Topeka, Kansas, 66606

  • University of Kansas Hospital-Westwood Cancer Center

    Westwood, Kansas, 66205

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: A Phase II Basket Trial of Glutaminase Inhibitor (BEGIN) Telaglenastat (CB-839) HCL in Patients With NF1 Aberrations, NF1 Mutant Malignant Peripheral Nerve Sheath Tumors (MPNST), KEAP1/NRF2 and LKB1 Aberrant Tumors

This phase II trial studies how well glutaminase inhibitor telaglenastat hydrochloride (CB-839 HCl) works in treating patients with specific genetic mutations and solid tumors or malignant peripheral nerve sheath tumors that have spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Glutaminase converts an amino acid (building block of proteins) called glutamine to glutamate, which can support several cellular pathways. Telaglenastat hydrochloride works by blocking glutamine activity needed for the growth of cells. When this activity is blocked, the growth of cancer cells may stop and the cancer cells may then die. Cancer is caused by changes (mutations) to genes that control the way cells function and uncontrolled cell growth may result in tumor formation. Specific genetic mutations studied in this clinical trial are NF1 mutation for malignant peripheral nerve sheath tumors, and NF1, KEAP1/NRF2, or STK11/LKB1 mutation for other solid tumors. Telaglenastat hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To assess the best overall response rate (BORR) achieved by 6 months of telaglenastat (CB-839) hydrochloride (HCl) treatment in specific pathway aberrant tumors (MPNST, NF1, KEAP1/NRF2 \& STK11/ LKB1).

SECONDARY OBJECTIVES:

  1. To determine the safety, progression-free survival (PFS), time to progression (TTP) and overall survival (OS).

II. To determine the overall response rate (ORR) (highest objective response achieved between start of therapy and progression), time to response (TTR) and clinical benefit rate (CBR) of telaglenastat (CB-839)HCl.

III. To assess pharmacodynamic changes and adaptive responses and correlate with response to treatment as well as disease progression (correlative objective).

EXPLORATORY OBJECTIVES:

  1. Correlate fludeoxyglucose F-18 (18-F FDG) positron emission tomography (PET)/computed tomography (CT) pre-therapy and 8-weeks post-therapy response to telaglenastat (CB-839) HCl therapy.

II. Evaluate changes in level of circulating tumor deoxyribonucleic acid (DNA) at baseline, one month on-treatment and time of progression (Molecular Characterization Laboratory [MoCHA Labs]) to treatment response.

III. Quantify the peripheral blood concentrations of the metabolites: aspartate, glutamate, glutamine and arginine (@Mayo clinic Oncometabolomics core) and correlate with response.

IV. Evaluate the pharmacodynamic (PD) effect of telaglenastat (CB-839) HCl on systemic levels of the tricarboxylic acid (TCA) cycle metabolites in peripheral blood (baseline and one month) as part of the protocol.

  1. Evaluate tumor by reverse phase protein array (@core facility at MD Anderson) and ribonucleic acid (RNA) sequencing (seq) to evaluate changes from pre-treatment, during treatment and post treatment specimens.

VI. Perform patient-derived tumor xenograft (PDX) modelling-co-clinical trials (@Dr. Funda Meric-Bernstam's lab MD Anderson) to understand response/resistance mechanisms and also evaluate combination therapies for future development.

OUTLINE:

Patients receive telaglenastat hydrochloride orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, magnetic resonance imaging (MRI), or PET/CT during screening and on study, and collection of blood samples during screening and on study.

After completion of study treatment, patients are followed up every 3 months thereafter.

Being tested
Biospecimen Collection, Computed Tomography, Magnetic Resonance Imaging, Pharmacodynamic Study, Positron Emission Tomography
Medical subject headings
Neoplasm Metastasis

What participants receive

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

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT or PET/CT

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Pharmacodynamic StudyOther

    Also called PHARMACODYNAMIC, Pharmacodynamic (PD) study

    Correlative studies

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET/CT

  • Telaglenastat HydrochlorideDrug

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

    Given PO

Study groups in NCT03872427
Study groupRoleWhat they receive
Treatment (telaglenastat hydrochloride)ExperimentalPatients receive telaglenastat hydrochloride PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, or PET/CT during screening and on study, and collection of blood samples during screening and on study.
Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Other: Pharmacodynamic Study; Procedure: Positron Emission Tomography; Drug: Telaglenastat Hydrochloride

What is being measured

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

  1. Best Overall Response Rate by 6 Months

    Best overall response rate (BORR) based on RECIST V1.1 achieved by 6 months of CB-839 HCl treatment

    Measured: Up to 6 months from treatment start date

Secondary outcomes (6)

  1. Incidence of Adverse Events

    Will be assessed by Common Terminology Criteria for Adverse Events version 5.0. Will tabulate toxicity by cohort, type, severity and attribution.

    Measured: Up to 2 years from treatment start date

  2. Progression-free Survival

    Will estimate using the Kaplan-Meier method with time zero set to cycle 1, day 1 (C1D1). Will estimate the medians and select probabilities along with 95% confidence intervals. If more than a handful of patients die without progression, will use Aalen-Johansen estimates to adjust for the competing risk of death.

    Measured: Time to progression or death whichever comes first, assessed up to 2 years from treatment start date

  3. Time to Progression

    Will estimate the medians and select probabilities along with 95% confidence intervals. If more than a handful of patients die without progression, will use Aalen-Johansen estimates to adjust for the competing risk of death.

    Measured: Time to progression starting at C1D1, assessed up to 2 years from treatment start date

  4. Overall Survival

    Will estimate using the Kaplan-Meier method with time zero set to C1D1. Will estimate the medians and select probabilities along with 95% confidence intervals. If more than a handful of patients die without progression, will use Aalen-Johansen estimates to adjust for the competing risk of death.

    Measured: Time to death from any cause, assessed up to 2 years from treatment start date

  5. Overall Response Rate

    Measured: From start of treatment until disease progression/recurrence, assessed up to 2 years

  6. Clinical Benefit Rate

    Measured: Up to 2 years from treatment start date

Timeline

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

  1. First posted13 Mar 2019
  2. Study start14 Dec 2019
  3. Primary completion30 Oct 2023
  4. Study completion16 Apr 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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03872427
Sponsor's protocol ID
NCI-2019-01365
Other IDs
NCI-2019-01365, NCI10220, 10220, 10220, UM1CA186688
Status last verified
Apr 2026
First submitted
12 Mar 2019
Last updated
31 Jul 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biospecimen Collection, Computed Tomography and Magnetic Resonance Imaging in people with Advanced Malignant Solid Neoplasm and Metastatic Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 31 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 22 inclusion and 9 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 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Best Overall Response Rate by 6 Months (time frame: Up to 6 months from treatment start date). 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 NCT03872427.

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 31 Jul 2026.

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