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

Running, not enrolling · Phase 2

Conditions studied: Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm, NF1 Mutation Positive Malignant Peripheral Nerve Sheath Tumor, Unresectable Malignant Solid Neoplasm

In brief

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.

Key facts

Study ID

NCT03872427

Run by

National Cancer Institute (NCI)

People needed

54

Starts

2019-12-14

Expected to finish

2027-04-16

Last updated by the study team

2026-07-31

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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
• 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

You may not qualify if…

• 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
• 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

Where it is running

• 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

Full record on ClinicalTrials.gov

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