Comparing 3 approaches for high grade glioma

Inclusion

• +For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2/3 of the pons, and histopathology consistent with diffuse WHO Grade 2-4 glioma.
• +Patients whose tumors harbor other alterations in addition to IDH1 mutation will potentially be eligible following consensus recommendation by the international multidisciplinary molecular screeningScreeningThe checks done before joining, to see whether a study fits.Read more → committee.
• +Patients with IDH2 mutations are not eligible.
• +Inclusion criteriaInclusion criteriaThe things you must have or be for a study to consider you.Read more → already met to enroll on TarGeT-SCR (central molecular and histopathologic screening) based on:
• +Age: patients must be ≥12 years and ≤39 years of age at the time of enrollmentEnrolmentThe number of participants a study plans to include, or has included.Read more → on TarGeT-SCR 1.2) Diagnosis:
• +Patients with a newly-diagnosed IDH1-mutant HGG including DIPG are eligible. All patients must have tumor tissue from diagnostic biopsy or resection, without exceptions. The diagnosis of HGG, including DIPG, must have been confirmed through TarGeT-SCR.
• +All other HGG must be WHO Grade 3 or 4.
• +Disease status: There are no disease status requirements for enrollment
• +Measurable disease is not required. Patients without measurable disease are eligible.
• +Primary spinal tumor: Patients with a primary spinal HGG are eligible.
• +Patient must not have metastatic disease.
• +Inclusion criteria for assignment to TarGeT-D, for all strata:
• +Presence of at Least One Relevant Actionable Somatic Mutation in IDH1 Gene, Detailed Here:
• +R132H, R132C, R132S, R132G or R132L.
• +Patients with oligodendroglioma, IDH-mutant and 1p/19q-codeleted are not eligible.
• +Weight: Patients must weigh ≥35 Kg (77 lbs) at the time of enrollment on TarGeT-D.
• +Performance Level: Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• +Patients in pre-maintenance phase must enroll and start treatment no later than 21 calendar days post-completion of RT.
• +Patients not in pre-maintenance phase must enroll and start treatment no later than 35 calendar days post-completion of RT.
• +Organ Function Requirements 2.5.1 Adequate Bone Marrow Function Defined as:
• +Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3.
• +Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
• +Hemoglobin \> 8 g/dL (may be transfused). 2.5.2 Adequate Renal Function Defined as
• +Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 OR
• +Maximum serum creatinine based on age/gender as follows: 10 to \< 13 yrs=1.2 mg/dL for males and females. 13 to \< 16 yrs=1.5 mg/dL for males and 1.4 mg/dL for females.
• +Adequate Liver Function Defined as:
• +Total bilirubin must be ≤ 1.5 × institutional ULN.
• +AST(SGOT)/ALT(SGPT) \< 3 × institutional ULN.
• +Alkaline Phosphatase \< 3 × institutional ULN. 2.5.4 Adequate Neurologic Function Defined as:
• +Patients with seizure disorder may be enrolled if well-controlled on anticonvulsants that are not a strong inducer or inhibitor of CYP3A4/5.
• +Patients must be able to swallow oral medications to be eligible for study enrollment.
• +Informed consentInformed consentThe process of being told what taking part involves, then choosing freely.Read more →: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
• +Prior Therapy 2.4.1 Surgery, radiation, and/or dexamethasone are permissible. Temozolomide administered concurrently with radiotherapy is permissible. Prior administration of bevacizumab is allowed, given at least 42-day washout periodWashout periodA gap with no treatment, so the previous one clears your system.Read more → is completed prior to beginning treatment on TarGeT-D. No other prior anticancer therapy for HGG will be allowed.
• +Radiation therapy requirements: RT, delivered via photon or proton beam, must have been administered at a standard dose including 54 Gy in 30 fractions for DIPG, 55-59.4 Gy in 30-33 fractions for other HGG or 45-54 Gy for primary spinal cord HGG. Any variances in the radiotherapy dose within 10% of the standard doses outlined above will be discussed with the Study Chair to confirm eligibilityEligibility criteriaThe full list of requirements for taking part in a study.Read more → prior to study enrollment.
• +Timing between diagnosis and start of RT: Patients must have started RT \< 42 calendar days of initial diagnosis defined as the date of diagnostic biopsy or resection; if a patient underwent two upfront surgeries (e.g., biopsy then resection or debulking), this is the date of the second surgery.