A Study to Evaluate CB-839 With Radiation Therapy and Temozolomide in Treating Participants With IDH-Mutated Diffuse Astrocytoma or Anaplastic Astrocytoma

Overview

  • Study type

    Interventional
  • Study phase

    I
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Jacksonville, Florida: 18-011454
    • Rochester, Minnesota: 18-011454
    • Scottsdale/Phoenix, Arizona: 18-011454
    NCT ID: NCT03528642
    Sponsor Protocol Number: NCI-2018-00876

About this study

The purpose of this study is to evaluate the side effects and best dose of  CB-839 hydrochloride (CB-839) in combination with radiation therapy and temozolomide in treating participants 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. Drugs used in chemotherapy, 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 stopping them from spreading. Giving CB-839 with radiation therapy and temozolomide may work better in treating participants with IDH-mutated diffuse astrocytoma or anaplastic astrocytoma.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility 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.
  • Patients must have been on a stable or decreasing dose of corticosteroids over the last 7 days.
  • Patients must have been on a stable or decreasing dose of antiepileptic therapy over the last 14 days. 
  • 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 administration.
  • Ability to understand and the willingness to sign a written informed consent document.

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 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. 
  • 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. 
  • 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 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, breastfeeding should be discontinued if the mother is treated with CB-839 HCl. These potential risks may also apply to TMZ.

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Kurt Jaeckle, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Sani Kizilbash, M.D., M.P.H.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Maciej Mrugala, M.D., Ph.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20461642

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