Overview

CB-839 With Radiation Therapy and Temozolomide in Treating Patients With IDH-Mutated Diffuse Astrocytoma or Anaplastic Astrocytoma

Status:
Recruiting
Trial end date:
2022-12-05
Target enrollment:
0
Participant gender:
All
Summary
This phase 1b trial studies the side effects and best dose of glutaminase inhibitor CB-839 hydrochloride (CB-839) in combination with radiation therapy and temozolomide in treating patients with IDH-mutated diffuse or anaplastic astrocytoma. CB-839 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Chemotherapy drugs, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving CB-839 with radiation therapy and temozolomide may work better than surgery, radiation therapy, and temozolomide in treating patients with IDH-mutated diffuse astrocytoma or anaplastic astrocytoma.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
National Cancer Institute (NCI)
Treatments:
Dacarbazine
Temozolomide
Criteria
Inclusion Criteria:

- Patients must have histopathologic or molecular confirmation of either IDH-mutant DA
or IDH-mutant AA. Acceptable IDH mutations for study eligibility include any IDH1
mutation at codon 132 or any IDH2 mutation at codon 172.

- Age >= 16 years. The intended neurocognitive tests have not been validated in children
below the age of 16.

- Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%).

- Hemoglobin > 9.0 g/dL

- Leukocytes >= 3.0 x 10^9/L

- Absolute neutrophil count >= 1.5 x 10^9/L

- Platelets >= 100 x 10^9/L

- International normalized ratio (INR) =< 1.5 x upper limit of normal (ULN)

- Partial thromboplastin time (PTT) or activated partial thromboplastin time (APTT) =<
1.5 x ULN

- Patients on a stable dose of anti-coagulation therapy will be allowed to participate
if they have no signs of bleeding or clotting and the INR/PT and PTT/aPTT results are
compatible with an acceptable risk-benefit ratio as per the investigator's discretion.

- Total bilirubin =< 1.5 x institutional ULN and < 3 mg/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

- Creatinine =< 1.5 x institutional ULN or creatinine clearance >= 60 mL/minute

- If there is history of human immunodeficiency virus (HIV) infection, patients must be
on effective antiretroviral therapy and HIV viral load must be undetectable within 6
months of study enrollment.

- If there is history of chronic hepatitis B virus (HBV) infection, patients must have
either been treated or are on suppressive therapy (as indicated), and HBV viral load
must be undetectable.

- If there is history of hepatitis C virus (HCV) infection, patients must have been
treated and HCV viral load must be undetectable.

- Patient must have measurable disease by RANO criteria (dose expansion cohort only).

- Patient must be at least 7 days beyond stereotactic biopsy and/or at least 14 days
beyond open craniotomy at the time of registration.

- Patients must have been on a stable or decreasing dose of corticosteroids over the
last 7 days at the time of registration.

- Patients must have been on a stable or decreasing dose of antiepileptic therapy over
the last 14 days at the time of registration.

- Females of childbearing potential must have a negative pregnancy test (=< 14 days)
prior to start of trial treatment. The effects of CB-839 HCl on the developing human
fetus are unknown. For this reason and because alkylating agents as well as TMZ 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 CB-839 HCl
(telaglenastat) administration.

- Ability to understand and the willingness to sign a written informed consent document.

- Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial.

- Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association functional classification. To be
eligible for this trial, patients should be class 2B or better.

- Availability of archival FFPE tumor tissue collected within 12 months prior to
registration.

Exclusion Criteria:

- Patients must not have received prior chemotherapy to treat the glioma.

- Patients who are receiving any other investigational agents.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to CB-839 HCl (telaglenastat) or TMZ.

- Patient must not have received prior radiation therapy to the brain. Prior radiation
therapy to the head and neck is also excluded if radiation fields overlap.

- No prior use of Gliadel wafers.

- Patient must have no evidence of either infratentorial or spinal involvement with
tumor.

- Patients who are unable to swallow tablets.

- Patients who are at risk for impaired absorption of oral medication including, but not
limited to, refractory vomiting, gastric resection/bypass, and duodenal/jejunal
resection.

- Patients with uncontrolled intercurrent illness.

- Patients with a "currently active" second malignancy other than non-melanoma skin
cancers. Patients are not considered to have a "currently active" malignancy if they
have completed therapy and are free of disease for more than 3 years.

- Pregnant women are excluded from this study because CB-839 HCl (telaglenastat) is an
agent with the potential for teratogenic or abortifacient effects. Because there is an
unknown but potential risk for AEs in nursing infants secondary to treatment of the
mother with CB-839 HCl (telaglenastat), breastfeeding should be discontinued if the
mother is treated with CB-839 HCl (telaglenastat). These potential risks may also
apply to TMZ.

- Adolescent patients who require sedation for magnetic resonance imaging (MRI) or
magnetic resonance spectroscopy (MRS).

- Patients with psychiatric illness/social situations that would limit compliance with
study requirements.

- The primary language of communication for the patient must be English (dose expansion
cohort only). The intended neurocognitive tests have not been validated in patients
who do not primarily speak English.