Talazoparib - Carboplatin for Recurrent High-grade Glioma With DDRd (NCT04740190) | Clinical Trial Compass
CompletedPhase 2
Talazoparib - Carboplatin for Recurrent High-grade Glioma With DDRd
Hong Kong33 participantsStarted 2021-01-01
Plain-language 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)
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. 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:
Exclusion criteria
✕. 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