Clinical Trials

Inclusion Criteria:

• At least 12 years of age.
• Weigh at least 40 kg.
• Be able to understand and willing to sign informed consent or assent as determined by local requirements and willing to comply with scheduled visits, treatment plans, procedures, and laboratory tests, including serial peripheral blood sampling and urine sampling, during the study. A legally authorized representative may consent on behalf of a subject who is otherwise unable to provide informed consent, if acceptable to and approved by the site and/or site’s institutional review board (IRB)/independent ethics committee (IEC). A parent or legal guardian must sign informed consent for adolescent subjects who sign assent.
  • Note: Subjects who do not read and/or speak one of the languages in which the HRQoL instruments are provided will be permitted to enroll and not complete these HRQoL outcome instruments, assuming all other eligibility criteria are met.
  • Be able to understand and willing to sign informed consent or assent as determined by local requirements and willing to comply with scheduled visits, treatment plans, procedures, and laboratory tests, including serial peripheral blood sampling and urine sampling, during the study. A legally authorized representative may consent on behalf of a subject who is otherwise unable to provide informed consent, if acceptable to and approved by the site and/or site’s institutional review board (IRB)/independent ethics committee (IEC). A parent or legal guardian must sign informed consent for adolescent subjects who sign assent.
  • Note: Subjects who do not read and/or speak one of the languages in which the HRQoL instruments are provided will be permitted to enroll and not complete these HRQoL outcome instruments, assuming all other eligibility criteria are met.
• Have Grade 2 oligodendroglioma or astrocytoma per WHO 2016 criteria. 
• Have had at least 1 prior surgery for glioma (biopsy, sub-total resection, gross-total resection), with the most recent surgery having occurred at least 1 year (-1 month) and not more than 5 years (+3 months) before the date of  randomization, and no other prior anticancer therapy, including chemotherapy and radiotherapy, and not be in need of immediate chemotherapy or radiotherapy in the opinion of the Investigator. (Note: Subjects undergoing biopsy solely to obtain tissue for central confirmation of IDH mutation status [eg, tissue from previous surgery was exhausted or not available] will be considered an exception and will not need to wait an additional year from biopsy to be eligible.) 
• Have confirmed IDH1 (IDH1 R132H/C/G/S/L mutation variants tested) or IDH2 (IDH2 R172K/M/W/S/G mutation variants tested) gene mutation status disease by central laboratory testing during the Prescreening period and available 1p19q status by local testing (eg, fluorescence in situ hybridization [FISH], comparative genomic hybridization [CGH] array, sequencing) using an accredited laboratory.
• Have MRI-evaluable, measurable, non-enhancing disease, as confirmed by the BIRC, assessed at Screening on 2D T2-weighted or 2D T2-weighted fluid-attenuated inversion recovery (FLAIR) MRI with ≤4 mm slice thickness and no interslice gap. Measurable non-enhancing disease is defined as at least 1 target lesion measuring ≥1 cm × ≥1 cm (bidimensional). Enhancement that is centrally confirmed by the BIRC to be minimal, non-nodular, and non-measurable and that has not changed between the 2 most recent scans (including screening scan) will be permitted. 
• Have a Karnofsky Performance Scale (KPS) (Appendix 11.8) score (for subjects ≥16 years of age) or Lansky Play Performance Scale (LPPS) (Appendix 11.7) score (for subjects <16 years of age) of ≥80%.
• Have expected survival of ≥12 months.
• Have adequate bone marrow function as evidenced by:
  • Absolute neutrophil count ≥ 1,500 mm^3 or ≥1.5 × 10^9/L
  • Hemoglobin ≥ 9 g/dL
  • Platelets ≥ 100,000 mm^3 or ≥ 100 × 10^9/L.
• Have adequate hepatic function as evidenced by:
  • Serum total bilirubin ≤1.5 × upper limit of normal (ULN) unless considered due to Gilbert’s disease after approval by the Medical Monitor; and
  • AST at or below ULN and ALT at or below ULN; and
  • Alkaline phosphatase (ALP) ≤2.5 × ULN.
• Have adequate renal function as evidenced by:
  • Serum creatinine ≤ 2.0 × ULN; OR
  • Creatinine clearance > 40 mL/min based on the Cockcroft-Gault glomerular filtration rate estimation: (140 – Age) × (Weight in kg) × (0.85 if female) / 72 × Serum Creatinine (for subjects ≥ 18 years of age). For subjects < 18 years of age, the Bedside Schwartz method (Schwartz and Work, 2009) is to be used: 0.413 × (Height in cm / Serum Creatinine in mg/dL).
• Have recovered from any clinically relevant toxicities associated with any prior surgery for the treatment of glioma unless stabilized under medical management.
• Female subjects of childbearing potential must have a negative serum pregnancy test before the start of therapy. Women of childbearing potential are defined as having had onset of their first menstrual period and have not undergone a hysterectomy or bilateral oophorectomy or are not naturally postmenopausal (ie, have not menstruated at all in the preceding 24 consecutive months). Women of childbearing potential as well as fertile men with partners who are women of childbearing potential must agree to abstain from sexual intercourse or to use 2 highly effective forms of contraception, at least one of which must be a barrier method, from the time of giving informed consent or assent, throughout the study, and for 90 days after the last dose of vorasidenib. Abstinence is acceptable only as true abstinence when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception. Highly effective forms of contraception are defined as hormonal oral contraceptives, injectables, patches, intrauterine devices, intrauterine hormone release systems, bilateral tubal ligation, condoms with spermicide, or male partner sterilization.

Exclusion Criteria:

• Have had any prior anticancer therapy other than surgery (biopsy, sub-total resection, gross-total resection) for treatment of glioma including systemic chemotherapy, radiotherapy, vaccines, small-molecules, IDH inhibitors, investigational agents, laser ablation, etc. 
• Have features assessed as high-risk by the Investigator, including brainstem involvement either as primary location or by tumor extension, clinically relevant functional or neurocognitive deficits due to the tumor in the opinion of the Investigator (deficits resulting from surgery are allowed), or uncontrolled seizures (defined as persistent seizures interfering with activities of daily life AND failed 3 lines of antiepileptic drug regimens including at least 1 combination regimen).
• Concurrent active malignancy except for:
  • curatively resected nonmelanoma skin cancer; or
  • curatively treated carcinoma in situ. Subjects with previously treated malignancies are eligible provided they have been disease-free for 3 years at Screening.
• Are pregnant or breastfeeding.
• Have an active infection that requires systemic anti-infective therapy or with an unexplained fever > 38.5°C within 7 days of C1D1.
• Have a known hypersensitivity to any of the components of vorasidenib.
• Have significant active cardiac disease within 6 months before the start of study treatment, including New York Heart Association Class III or IV congestive heart failure, myocardial infarction, unstable angina, and/or stroke.
• Have LVEF < 40% by echocardiogram (ECHO) (or by other methods according to institutional practice) obtained within 28 days before the start of study treatment.
• Have a heart-rate corrected QT interval using Fridericia’s formula (QTcF) ≥ 450 msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome). Subjects with bundle branch block and prolonged QTcF are permitted with approval of the Medical Monitor.
• Are taking therapeutic doses of steroids for signs/symptoms of glioma. Subjects taking physiologic doses (defined as equivalent of ≤ 10 mg prednisone daily) for medical conditions not related to glioma will be permitted.
• Are taking any medications that are cytochrome P450 (CYP) 2C8, CYP2C9, CYP2C19, or CYP3A substrates with a narrow therapeutic index. (Subjects should be transferred to other medications before receiving the first dose of study drug.)
• Have known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, known positive human immunodeficiency virus antibody results, or AIDS-related illness. Subjects with a sustained viral response to HCV treatment or immunity to prior HBV infection will be permitted. Subjects with chronic HBV that is adequately suppressed by institutional practice will be permitted.
• Have known active inflammatory gastrointestinal disease, chronic diarrhea, previous gastric resection or lap band dysphagia, short-gut syndrome, gastroparesis, or other condition that limits the ingestion or gastrointestinal absorption of drugs administered orally. Gastroesophageal reflux disease under medical treatment is allowed (assuming no drug interaction potential).
• Have any other acute or chronic medical or psychiatric condition, including recent (within 12 months of C1D1) or active suicidal ideation or behavior, or a laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.

Eligibility last updated 8/11/21.  Questions regarding updates should be directed to the study team contact.