Testing Whether Cancers With Specific Mutations Respond Better to Glutaminase Inhibitor, Telaglenastat Hydrochloride, Anti-Cancer Treatment, BeGIN Study
NCT ID: NCT03872427
Last Updated: 2025-11-14
Study Results
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View full resultsBasic Information
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ACTIVE_NOT_RECRUITING
PHASE2
54 participants
INTERVENTIONAL
2019-12-14
2026-04-16
Brief Summary
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Detailed Description
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I. 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:
I. 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:
I. 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.
V. 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.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment (telaglenastat hydrochloride)
Patients 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.
Biospecimen Collection
Undergo collection of blood
Computed Tomography
Undergo CT or PET/CT
Magnetic Resonance Imaging
Undergo MRI
Pharmacodynamic Study
Correlative studies
Positron Emission Tomography
Undergo PET/CT
Telaglenastat Hydrochloride
Given PO
Interventions
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Biospecimen Collection
Undergo collection of blood
Computed Tomography
Undergo CT or PET/CT
Magnetic Resonance Imaging
Undergo MRI
Pharmacodynamic Study
Correlative studies
Positron Emission Tomography
Undergo PET/CT
Telaglenastat Hydrochloride
Given PO
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
Exclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Funda Meric-Bernstam
Role: PRINCIPAL_INVESTIGATOR
University of Texas MD Anderson Cancer Center LAO
Locations
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University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, United States
Moffitt Cancer Center-International Plaza
Tampa, Florida, United States
Moffitt Cancer Center - McKinley Campus
Tampa, Florida, United States
Moffitt Cancer Center
Tampa, Florida, United States
Northwestern University
Chicago, Illinois, United States
University of Kansas Clinical Research Center
Fairway, Kansas, United States
HaysMed
Hays, Kansas, United States
University of Kansas Cancer Center
Kansas City, Kansas, United States
The University of Kansas Cancer Center - Olathe
Olathe, Kansas, United States
Mercy Hospital Pittsburg
Pittsburg, Kansas, United States
Salina Regional Health Center
Salina, Kansas, United States
University of Kansas Health System Saint Francis Campus
Topeka, Kansas, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States
National Cancer Institute Developmental Therapeutics Clinic
Bethesda, Maryland, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
University Health Truman Medical Center
Kansas City, Missouri, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, United States
Wake Forest University at Clemmons
Clemmons, North Carolina, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States
M D Anderson Cancer Center
Houston, Texas, United States
Countries
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Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Document Type: Informed Consent Form
Other Identifiers
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NCI-2019-01365
Identifier Type: REGISTRY
Identifier Source: secondary_id
NCI10220
Identifier Type: -
Identifier Source: secondary_id
10220
Identifier Type: OTHER
Identifier Source: secondary_id
10220
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2019-01365
Identifier Type: -
Identifier Source: org_study_id
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