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Clinical Trial 19956

Cancer Type: Neurologic Oncology
Interventions:CB-839; Temodal (Temozolomide); Temozolomide

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • Solmaz Sahebjam

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

A Phase 1b Trial of CB-839 in Combination with Radiation Therapy and Temozolomide in Patients with IDH-mutated Diffuse Astrocytoma and Anaplastic Astrocytoma

Summary

Objective

Primary Objective 1.1.1 Determine the MTD and/or the recommended Phase 2 dose (RP2D) of CB-839 HCl when combined with RT and TMZ in patients with newly diagnosed IDH-mutated diffuse DA and AA. Secondary Objectives 1.2.1 To observe and record anti-tumor activity. Although the clinical benefit of these drugs has not yet been established, the intent of offering this treatment is to provide a possible therapeutic benefit, and thus the patient will be carefully monitored for tumor response and symptom relief in addition to safety and tolerability. - The anti-tumor activity will be estimated by the objective response rate (ORR) and the clinical benefit rate (CBR) for the combination of CB-839 HCl and RT/TMZ in IDH-mutated glioma based on Response Assessment in Neuro-Oncology (RANO) criteria. 1.2.2 Determine the safety and tolerability of RT/TMZ/CB-839 HCl in patients based on physician reported adverse event (AE) data. Determine the safety and tolerability of RT/TMZ/CB-839 HCl in patients based on physician reported adverse event (AE) data. 1.2.3 Estimate the 2-year progression-free survival (PFS2) of RT/TMZ/CB-839 HCl in patients with IDH-mutated glioma based on RANO criteria. 1.2.4 Estimate the 2-year overall survival (OS2) of RT/TMZ/CB-839 HCl in patients with IDH-mutated glioma based on RANO 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.
  • Adequate organ & bone marrow function
  • 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.
  • 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 (=> 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.