Zotiraciclib (TG02) Plus Dose-Dense or Metronomic Temozolomide Followed by Randomized Phase II Trial of Zotiraciclib (TG02) Plus Temozolomide Versus Temozolomide Alone in Adults With Recurrent Anaplastic Astrocytoma and Glioblastoma

Background: Zotiraciclib (TG02) is an investigational drug that penetrates the blood-brain barrier and might treat brain tumors. Temozolomide (TMZ) is a drug used to treat brain tumors. Objective: To find out if Zotiraciclib (TG02) is safe, and to find out if it in combination with TMZ is as effective as TMZ alone in people with brain tumors. Eligibility: People ages 18 and older with a brain tumor that has progressed after standard treatment Design: In phase I part, the Bayesian optimal interval (BOIN) design will be used to find the maximum tolerated dose (MTD) of Zotiraciclib (TG02) for Arm 1 (dose dense TMZ) and Arm 2 (metronomic TMZ) independently. Then a randomized cohort expansion compared progression free survival at 4 months (PFS4) of the two arms for an efficient determination of a TMZ schedule to combine with Zotiraciclib at MTD. In Phase II part, a Bayesian design based on posterior probability will be used to monitor efficacy. Participants will be screened with: * Medical history * Physical exam * Blood and urine tests * Magnetic resonance imaging (MRI) of the brain if they have not had one in 14 days * Heart test * Tissue sample from prior surgeries Participants will take Zotiraciclib (TG02) plus TMZ by mouth in 28-day cycles. * Some will take TMZ for 7 days on and 7 days off. Others will take it every day. * They will all take Zotiraciclib (TG02) three days before Cycle 1, and then on four days during every cycle. * They will all get treatment to prevent vomiting and diarrhea before and for 24 hours after each Zotiraciclib (TG02) dose. * They will all keep a diary of when they take the drugs and their symptoms. Participants will have study visits. These include: * Physical exam, heart test, quality of life questionnaire, brain MRI, and urine tests every 4 weeks * Blood tests every 2 weeks Participants will continue treatment until their disease gets worse or they have intolerable side effects. Participants will also be enrolled in anot