Telaglenastat With Radiation Therapy and Temozolomide in Treating Patients With IDH-Mutated Diffuse Astrocytoma or Anaplastic Astrocytoma
A Phase 1b Trial of Telaglenastat (CB-839) HCI in Combination With Radiation Therapy and Temozolomide in Patients With IDH-Mutated Diffuse Astrocytoma and Anaplastic Astrocytoma
4 other identifiers
interventional
40
1 country
25
Brief Summary
This phase 1b trial studies the side effects and best dose of telaglenastat in combination with radiation therapy and temozolomide in treating patients with IDH-mutated diffuse or anaplastic astrocytoma. Telaglenastat 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 telaglenastat 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started May 2019
Longer than P75 for phase_1
25 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 17, 2018
CompletedFirst Posted
Study publicly available on registry
May 18, 2018
CompletedStudy Start
First participant enrolled
May 1, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 8, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 8, 2026
April 13, 2026
January 1, 2026
7 years
May 17, 2018
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D)
MTD is defined as the dose level below the lowest dose that induces dose limiting toxicity (DLT) in at least 2 patients (out of 6). A total of 6 patients must be treated at the MTD. It is possible that the MTD will be unknown after this study (e.g., if the highest tested dose has fewer than 2 patients with DLT, out of 6). In this case, the highest dose is defined as the RP2D. A 3 + 3 cohort expansion design to determine toxicity-based dose escalation of telaglenastat (CB-839) hydrochloride (HCl) and external beam fractionated radiation therapy (RT) with concurrent temozolomide (TMZ) among patients with IDH-mutated diffuse astrocytoma (DA) or anaplastic astrocytoma (AA).
Up to 6.5 weeks
Secondary Outcomes (10)
Objective response rate (ORR) as defined by Response Assessment in Neuro-Oncology (RANO) criteria
Up to 6 months from the start of study treatment
Clinical benefit rate (CBR) as defined by RANO criteria
Up to 6 months from the start of study treatment
Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE)
Up to 2 years
Progression-free survival (PFS2) as defined by response assessment in neuro-oncology (RANO) criteria
Up to 2 years
Overall survival (OS2) as defined by RANO criteria
Up to 2 years
- +5 more secondary outcomes
Study Arms (1)
Treatment (telaglenastat, temozolomide, RT)
EXPERIMENTALPatients receive telaglenastat PO BID 7 days a week, temozolomide PO QD 7 days a week, and undergo RT 5 days a week for up to 5.5 weeks (diffuse astrocytoma) or 6.5 weeks (anaplastic astrocytoma) in the absence of disease progression or unacceptable toxicity.
Interventions
Given PO
Undergo RT
Given PO
Eligibility Criteria
You may qualify if:
- 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 (within 14 days prior to registration)
- Leukocytes \>= 3.0 x 10\^9/L (within 14 days prior to registration)
- Absolute neutrophil count \>= 1.5 x 10\^9/L (within 14 days prior to registration)
- Platelets \>= 100 x 10\^9/L (within 14 days prior to registration)
- International normalized ratio (INR) =\< 1.5 x upper limit of normal (ULN) (within 14 days prior to registration)
- Partial thromboplastin time (PTT) or activated partial thromboplastin time (APTT) =\< 1.5 x ULN (within 14 days prior to registration)
- 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 (within 14 days prior to registration)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) \& alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN (within 14 days prior to registration)
- 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.
- +10 more criteria
You may not qualify if:
- 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 telaglenastat (CB-839) HCl 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 telaglenastat (CB-839) HCl 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 telaglenastat (CB-839) HCl, breastfeeding should be discontinued if the mother is treated with telaglenastat (CB-839) HCl. 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (25)
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054, United States
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259, United States
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sani H Kizilbash
Mayo Clinic Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 17, 2018
First Posted
May 18, 2018
Study Start
May 1, 2019
Primary Completion (Estimated)
May 8, 2026
Study Completion (Estimated)
May 8, 2026
Last Updated
April 13, 2026
Record last verified: 2026-01