Talazoparib - Carboplatin for Recurrent High-grade Glioma With DDRd

NCT04740190 | Completed Phase 2 FDA Drug

• 1 other identifier: UW-20396
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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)

Conditions

Recurrent Glioma; Recurrent Glioblastoma; Poly ADP Ribose Polymerase (PARP) Inhibitor; PTEN Gene Inactivation; IDH Mutation

Keywords

recurrent glioblastoma; recurrent glioma; PARP inhibitor; IDH mutation; PTEN gene inactivation; BRCAness; DNA Damage Repair Deficiency

Outcome Measures

Primary Outcomes (1)

• Progression free survival in 6 months

  Free from disease progression based on RANO criteria

  6 month

Secondary Outcomes (3)

• Overall survival

  1 year

• Objective response rate

  1 year

• Duration of response

  1 year

Study Arms (1)

interventional arm

EXPERIMENTAL

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

Drug: Talazoparib

Interventions

Talazoparib DRUG

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

Also known as: Carboplatin, whole brain irradiation

interventional arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histopathologically proven diagnosis of WHO grade 3-4 glioma
• Tumor with one or more putatively pathogenic mutations or homozygous deletion in the genes associated with DDR or genomic instability, as listed below, will be eligible for the study. Genetic analysis on tumor tissue should be performed with next-generation-sequencing (NGS) based analysis to screen for the following genomic aberrations, which included,
• IDH mutation
• PTEN mutation
• "BRCAness" signature (ATM, ATR, BAP1, BRCA1, BRCA2, CDK12, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCE, FANCF, PALB2, NGS1, WRN, RAD50, RAD51B, RAD51C, RAD51D, MRE11A, BLM, BRIP1) The molecular profiling results will be considered eligible for screening only if they are performed in laboratories accredited by the College of American Pathologists (CAP) and certified to meet Clinical Laboratory Improvement Amendments (CLIA).
• Patients will be eligible if the original histology was lower-grade glioma and a subsequent diagnosis of glioblastoma or gliosarcoma is made.
• Patients who did not have recent surgery for their glioblastoma must have shown unequivocal radiographic evidence for tumor progression by contrast-enhanced MRI scan (or CT scan for patients with non-compatible devices) within 21 days prior to registration. Patients who did have surgery with a post-operative contrast-enhanced scan falling outside the 5-week window prior to registration, must have a repeat MRI scan (or CT scan for patients with non-compatible devices) within 21 days prior to registration.
• Patients must have passed an interval of 6 months or greater between completion of prior radiotherapy and registration. If patients have not passed an interval of at least 6 months, they may still be eligible if they meet one or more of the following criteria:
• New areas of tumor outside the original radiotherapy fields as determined by the investigator, or
• Histologic confirmation of tumor through biopsy or resection, or
• Nuclear medicine imaging, MR spectroscopy, or MR perfusion imaging consistent with true progressive disease, rather than radiation necrosis obtained within 28 days of registration AND an interval of at least 90 days between completion of radiotherapy and registration.
• Patients unable to undergo MR imaging because of non-compatible devices can be enrolled provided CT scans are obtained and are of sufficient quality. Patients without non-compatible devices may not use CT scans performed to meet this requirement.
• Prior history of standard dose CNS radiation of 50-60Gy in 25-30 fractions, or 40Gy in 15 Fractions.
• Patients must have recovered from the toxic effects of prior therapy, and there must be a minimum time of 28 days prior to registration from the administration of any investigational agent or prior cytotoxic therapy with the following exceptions:
• days from administration of vincristine

You may not qualify if:

• Prior therapy with PARP inhibitor
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1 year (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible).
• Severe, active co-morbidity, defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to registration
• Transmural myocardial infarction within the last 6 months prior to registration
• History of stroke or transient ischemic attack within 6 months prior to registration.
• Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically
• Significant peripheral vascular disease.
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
• Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring
• Hospitalization or precluding study therapy at the time of registration
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function other than screening panel and
• Coagulation parameters are not required for entry into this protocol.
• Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients.

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

Department of Clinical Oncology

Hong Kong, Hong Kong

Location

MeSH Terms

Conditions

Glioma; Glioblastoma

Interventions

talazoparib; Carboplatin

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• Aya Helali, MD, PhD

  Department of Clinical Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2021
• First Posted: February 5, 2021
• Study Start: January 1, 2021
• Primary Completion: December 14, 2023
• Study Completion: December 14, 2023
• Last Updated: June 11, 2025

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)