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

NCT03872427 | Active Not Recruiting Phase 2 Results FDA Drug

• 4 other identifiers: NCI-2019-01365NCI1022010220UM1CA186688
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 31

Brief 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 (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.

Conditions

Advanced Malignant Solid Neoplasm; Metastatic Malignant Solid Neoplasm; NF1 Mutation Positive Malignant Peripheral Nerve Sheath Tumor; Unresectable Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (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

  Up to 6 months from treatment start date

Secondary Outcomes (6)

• Incidence of Adverse Events

  Up to 2 years from treatment start date

• Progression-free Survival

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

• Time to Progression

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

• Overall Survival

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

• Overall Response Rate

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

Other Outcomes (3)

• Pharmacodynamic (PD) Tumor Oncometabolite Levels of Glutamine

  Baseline up to between 0-8 hours post-glutaminase inhibitor CB-839 hydrochloride dose

• PD Tumor Oncometabolite Levels of Glutamate

  Baseline up to between 0-8 hours post-glutaminase inhibitor CB-839 hydrochloride dose

• PD Tumor Oncometabolite Levels of Aspartate

  Baseline up to between 0-8 hours post-glutaminase inhibitor CB-839 hydrochloride dose

Study Arms (1)

Treatment (telaglenastat hydrochloride)

EXPERIMENTAL

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.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Other: Pharmacodynamic Study; Procedure: Positron Emission Tomography; Drug: Telaglenastat Hydrochloride

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (telaglenastat hydrochloride)

Computed Tomography PROCEDURE

Undergo CT or PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (telaglenastat hydrochloride)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (telaglenastat hydrochloride)

Pharmacodynamic Study OTHER

Correlative studies

Also known as: PHARMACODYNAMIC, Pharmacodynamic (PD) study

Treatment (telaglenastat hydrochloride)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Treatment (telaglenastat hydrochloride)

Telaglenastat Hydrochloride DRUG

Given PO

Also known as: CB-839 HCl, Glutaminase Inhibitor CB-839 Hydrochloride

Treatment (telaglenastat hydrochloride)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (31)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

UM Sylvester Comprehensive Cancer Center at Aventura

Aventura, Florida, 33180, United States

Location

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, 33146, United States

Location

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, 33442, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

UM Sylvester Comprehensive Cancer Center at Kendall

Miami, Florida, 33176, United States

Location

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, 33324, United States

Location

Moffitt Cancer Center-International Plaza

Tampa, Florida, 33607, United States

Location

Moffitt Cancer Center - McKinley Campus

Tampa, Florida, 33612, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Kansas Clinical Research Center

Fairway, Kansas, 66205, United States

Location

HaysMed

Hays, Kansas, 67601, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

The University of Kansas Cancer Center - Olathe

Olathe, Kansas, 66061, United States

Location

Mercy Hospital Pittsburg

Pittsburg, Kansas, 66762, United States

Location

Salina Regional Health Center

Salina, Kansas, 67401, United States

Location

University of Kansas Health System Saint Francis Campus

Topeka, Kansas, 66606, United States

Location

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205, United States

Location

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

National Cancer Institute Developmental Therapeutics Clinic

Bethesda, Maryland, 20892, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University Health Truman Medical Center

Kansas City, Missouri, 64108, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

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

New York, New York, 10032, United States

Location

Wake Forest University at Clemmons

Clemmons, North Carolina, 27012, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Specimen Handling; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Results Point of Contact

• Title: Dr. Funda Meric-Bernstam
• Organization: The University of Texas MD Anderson Cancer Center

fmeric@mdanderson.org

(713) 794-1226

Study Officials

• Funda Meric-Bernstam

  University of Texas MD Anderson Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2019
• First Posted: March 13, 2019
• Study Start: December 14, 2019
• Primary Completion: October 30, 2023
• Study Completion (Estimated): April 16, 2027
• Last Updated: May 4, 2026
• Results First Posted: July 1, 2025

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (31)