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Clinical Trial 20347

Cancer Type: Sarcoma
Study Type: Treatment
NCT#: NCT03872427

Phase: Phase II
Prinicipal Investigator:

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Overview

Study Title

A phase 2 basket trial of glutaminase inhibitor (BeGIN) CB-839 HCl in patients with NF1 Aberrations, NF1 mutant malignant peripheral nerve sheath tumors (MPNST), KEAP1/NRF2 and LKB1 Aberrant tumors

Summary

This phase II trial studies how well glutaminase inhibitor CB-839 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. CB-839 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. CB-839 HCl may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Objective

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

Treatments

Therapies

Medications

CB-839 HCl ()

Inclusion Criteria

  • Participants must have histologically confirmed malignancy that is metastatic or unresectable
  • Participant 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.)
  • Participant must have no standard therapies available
  • Participants for NF1 mutant MPNST and NF1 mutant non-MPNST cohorts must be >= 40 kg
  • Participant must be at least 4 weeks since any prior surgery or radiotherapy
  • Females of childbearing potential must have a negative serum pregnancy test (=> RECIST measurable disease and biopsiable targetable lesion
  • Participants 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
  • Participants 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 Participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • Eastern Cooperative Oncology Group (ECOG) performance status == 60%)
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,000/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin => Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) => Creatinine => Glomerular filtration rate (GFR) >= 30 mL/min/1.73 m^2 for Participants with creatinine levels above institutional normal

  • Exclusion Criteria

  • Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
  • Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1)
  • Participants who are receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to CB-839 HCl
  • Participants with glioma will be excluded
  • Participants with active or prior history of hepatitis B or C will be excluded
  • CB-839 HCl is a weak in vitro inhibitor of CYP2C9. Therefore, Participants 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 Participant 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 Participant 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 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 CB-839 HCl, breastfeeding should be discontinued if the mother is treated with CB-839 HCl

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