Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioblastoma

Glioma

Disease Attributes

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Carboplatin

Talazoparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Single fraction, low dose (2Gy) whole brain radiation therapy, followed by combination talazoparib and carboplatin

low dose whole brain radiation, followed by combination talazoparib and carboplatin

Aya Helali, MD, PhD

ECL Kwan, BSc

Tai-Chung Lam, FRCR

Chi-Leung Chiang, FRCR

Tsz-Him So, MBBS

In view of the strong biological rationale of employing PARP inhibition in high grade glioma, the current study purposes testing of talazoparib in a biomarker-enriched group of glioma. Carboplatin will be added to sensitize the tumor to PARP inhibition, and low dose radiation therapy will be applied to increase talazoparib drug penetration through blood-brain barrier. The goal is to estimate the effect size of such combinational treatment approach in recurrent high-grade glioma with DNA damage repair deficiency (dDDR)

Recurrent high grade glioma with dDDR, defined by genomic aberrations associated including IDH mutation, PTEN mutation and "BRCAness" signature as defined by next-generation-sequencing (NGS) based comprehensive genomic profiling, will be enrolled.

Patients will receive treatment in 7-day cycle. D1-4: Oral talazoparib 0.75mg daily; D1: Carboplatin (AUC 1.5). On cycle 1 day 1 low dose whole radiation radiation therapy will be given to increase drug penetration. Primary outcome is 6-month progression free survival (PFS-6) by RANO criteria. The study intended to recruit 33 subjects

Talazoparib - Carboplatin for Recurrent High-grade Glioma With DDRd

Combination Talazoparib - Carboplatin for Recurrent High-grade Glioma With DNA Damage Repair Deficiency (DDRd)

Free from disease progression based on RANO criteria

from date of study enrollment to the date of death from any cause

The percentage of patients with radiologically complete or partial response as determined by the investigator according to RANO criteria

The time interval between the time patient develops radiologically complete or partial response to disease progression according to RANO criteria

Spots Global Cancer Trial Database for pten gene inactivation