Brain and Neurologic Cancer

See protocol for full list:
Inclusion Parts 2 and 3 - - (KPS) score 60 or greater.
Inclusion Criteria Part 2
- Expected survival of 6 months or more
- IDH-mutant Grade 2, Grade 3, or Grade 4 astrocytoma
- IDH1 mutation
- Pts w/ Grade 2 or 3 astrocytoma must have 1 or more of the following risk factors: a) Unequivocal contrast enhancement on any MRI prior to resection b) Min 1×1 cm of residual tumor after resection, measurable. A pre-operative scan, if available and ideally taken within 48 hours prior to surgery, and a scan taken after the most recent surgery but prior to the start of radiotherapy, must be submitted to BICR for confirmation. c) A hemizygous deletion of, or known/predicted pathogenic mutation in CDKN2A/B. d) An amplification of PDGFRA, CCND2, CDK4, CDK6, MYC, or MYCN. e) A methylation profile congruent with a high-risk/high-grade IDH-mutant astrocytoma based on a validated methylation classifier
- at least 1 resection and/or biopsy. Re-resection is permitted only if it precedes the use of chemotherapy or radiotherapy.
-Must not have tumor recurrence or progression between first day of radiotherapy and randomization by local assessment
- completed radiation therapy with a min of 80% of planned treatment completed (with or without concurrent temozolomide) and between 6 and 12 cycles of adjuvant temozolomide, without any breaks between doses of temozolomide greater than 60 days.
Inclusion Part 3 Only
- Expected survival greater / equal to12 months at the time of signing the ICF.
- had at least 1 prior surgery for glioma (biopsy, sub-total resection, or gross total resection), with the most recent surgery having occurred at least 90 days and no longer than 5 years before the date of enrollment, have not had any other prior anticancer therapy, including chemotherapy and radiotherapy, and are not in need of immediate chemotherapy or radiotherapy in the opinion of the Investigator.
- histologically confirmed Grade 3 IDH-mutant oligodendroglioma according to WHO 2021 criteria
- residual or recurrent measurable disease
- IDH1 mutation (R132H/C/G/S/L). The presence of 1p19q co-deletion must also be confirmed. Exclusion (Parts 2 and 3)
-prior or anticipated treatment with anti-angiogenic agents such as Avastin (bevacizumab), agents known to target IDH1 or IDH2, or investigational agents for glioma are excluded.
Exclusion Criteria for Part 2
- Participants may not have received any anticancer treatments other than surgery, radiation, concurrent/adjuvant temozolomide, and tumor-treating fields. Tumor-treating fields (TTFs) must be discontinued prior to randomization.
Exclusion Criteria for Part 3
- Participants may not have had any prior anticancer therapy other than surgery (biopsy, sub-total, or gross total resection) for treatment of glioma, including radiotherapy

Inclusion
1. histologically, molecularly, or cytologically confirmed recurrent astrocytic tumors including:
• GBM or variants, IDH-wildtype, grade 2-4 (standard curative measures available or not)
• Astrocytoma, IDH-mutant, grade 2-4 (standard curative measures available or not)
• Diffuse midline gliomas, including pediatric-type H3K G34 or E3 K27 mutant tumors
2. Tumors ≤6 cm in maximal diameter.
3. At least a 6-month break from last dose of radiation therapy.
4. ECOG performance status ≤2 (Karnofsky ≥60%)

Exclusion:
1. Actively taking medications that are known to induce methemoglobinemia (e.g. sulfonamides, nitrofurans, anti-malarials [primaquine, chloroquine], cyclophophsamide, and ifosfamide).
2. History of allergic reactions attributed to compounds of similar chemical or biologic composition to triapine.
3. Known G6PD deficiency. Testing for G6PD deficiency is not required

Presumed diagnosis of glioblastoma IDH-wt (as per the 2021 WHO Classification of CNS Tumors) deemed to be potentially resectable and deemed to be a good candidate for post-operative standard of care temozolomide and radiation therapy.

--Surgical objective is for gross total resection (GTR)/near-total resection (NTR) de-fined as  95% of contrast enhancing (CE) tumor removed plus  1 cm3 residual CE tumor. Patients with subtotal resection will still be eligible if at least 70% of the CE tumor is resected.

--Eligibility will be confirmed after surgery when diagnosis of glioblastoma IDH-wt confirmed prior to randomization. Randomization can occur with only IDH1 im-munohistochemistry and when additional molecular testing is available, if glioblastoma IDH-wt is not confirmed, the participant will be deemed a screen failure and replaced.

--Patients with prior biopsy or subtotal resection are eligible if no other anti-cancer treatment received for glioblastoma and additional resection indicated