Overview

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

Status:
Completed

Trial end date:
2020-08-26

Target enrollment:

Participant gender:

Summary

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 another protocol to test molecular markers for their brain tumor.

Phase:

Phase 1/Phase 2

Details

Lead Sponsor:

National Cancer Institute (NCI)

Treatments:

Temozolomide