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

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.

Conditions

• Brain Tumor
• Astrocytoma
• Astroglioma
• Glioblastoma
• Gliosarcoma

Interventions

DRUG

Zotiraciclib (TG02)

Phase I: Two treatment arms and several dose levels are planned; In the maximum tolerated dose (MTD) finding part, Temozolomide (TMZ) with two alternate schedules (dose dense (dd) and metronomic (mn) in combination with Zotiraciclib (TG02) will be administered; --A cohort extension of both arms will be performed at each MTD and the treatment arm with a better progression free survival at 4 months (PFS4) will be selected for the combination treatment arm for Phase II; Patients will be randomized between two competing treatment arms: (winner of dd vs mn) TMZ + Zotiraciclib (TG02) versus dd/mn TMZ alone using a Bayesian clinical trial design. The dosage for the combination arm will be derived from the MTD determined in the Phase I component of the study.

DRUG

Temozolomide (TMZ)

Phase I: In the maximum tolerated dose (MTD) finding part, Temozolomide (TMZ) with two alternate schedules (dose dense (dd) and metronomic (mn) in combination with Zotiraciclib (TG02) will be administered; A cohort extension of both arms will be performed at each MTD and the treatment arm with a better progression free survival at 4 months (PFS4) will be selected for the combination treatment arm for Phase II; Patients will be randomized between two competing treatment arms: ("winner" of dd vs mn) TMZ + Zotiraciclib (TG02) versus dd/mn TMZ alone using a Bayesian clinical trial design.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Jing Wu, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-12-14

Primary Completion

2020-08-26

Completion

2020-08-26

FDA Drug

Yes

Countries

• United States

Study Locations