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| Name | Class |
|---|---|
| The Ben & Catherine Ivy Foundation | OTHER |
| American Society of Clinical Oncology | OTHER |
| Barbara Ann Karmanos Cancer Institute | OTHER |
| Translational Genomics Research Institute |
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This study would test how much of the new drug, AZD1775, is present in tumor, blood, and skin after one dose of the drug.
The purpose of the study is not to treat the tumor, but to see if the drug actually gets into the tumor cells. This study does not replace routine cancer treatment.
Patients will be administered one dose of AZD1775 prior to surgical resection of their tumor. There will be 2 portions of this trial, referred to as Part 1 and Part 2. Part 1 will involve a dose escalation strategy where 3 separate doses (100, 200, and 400mg) will be evaluated. Each dose cohort will involve 4 patients. Surgery, with tissue harvest for determination of both tissue drug level and biomarker evaluation, will occur at 8 hrs post drug administration.
Part 2 will determine the potential tumor drug level and PD effects at various time intervals after drug administration of a single select drug dose. Currently, we are planning to use a dose (200 mg) that has been deemed safe when used in combination with cytotoxic therapy. However, if results from Part 1 suggest an alternate dose may be preferable, we will consider using that alternate dose in Part 2. Dosing will be followed by surgical resection at 2-4 hrs and at 22-26 hrs post dose.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AZD1775 | Experimental | Patients will receive a single dose (either 100 mg, 200 mg or 400 mg) of AZD1775, an oral agent, prior to surgery for resection of GBM |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD1775 | Biological | All patients receive a single dose of the oral study drug prior to surgery for resection of GBM. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Plasma concentration of AZD1775 following single dose of AZD1775 | Will be summarized using descriptive statistics | at baseline, 2-4, 8-12, and 22-26 hours following single dose of AZD1775 |
| Intratumoral concentration of AZD1775 | Will be summarized using descriptive statistics | up to day of surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Degree of CDC2 (Tyr15) phosphorylation in tissue | Will be summarized using descriptive statistics | at baseline and up to 26 hours post dosing |
| Number of GBM cells in M-phase of cell cycle (PH3) |
| Measure | Description | Time Frame |
|---|---|---|
| P53 mutation status | Will be summarized using descriptive statistics | up to time of surgery |
| Presence of checkpoint regulator genes in GBM specimens | checkpoint regulator genes in GBM specimens |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nader Sanai, MD | Barrow Neurological Institute at St.Joseph's Hospital Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Barrow Neurological Institute at St. Joseph's Hospital Medical Center | Phoenix | Arizona | 85013 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29798906 | Derived | Sanai N, Li J, Boerner J, Stark K, Wu J, Kim S, Derogatis A, Mehta S, Dhruv HD, Heilbrun LK, Berens ME, LoRusso PM. Phase 0 Trial of AZD1775 in First-Recurrence Glioblastoma Patients. Clin Cancer Res. 2018 Aug 15;24(16):3820-3828. doi: 10.1158/1078-0432.CCR-17-3348. Epub 2018 May 24. |
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| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
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| ID | Term |
|---|---|
| C549567 | adavosertib |
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| OTHER |
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Will be summarized using descriptive statistics
| at baseline and up to 26 hours post dose AZD1775 |
| Presence of double-strand DNA damage (γH2AX). | Will be summarized using descriptive statistics | at baseline and up to 26 hours post dose AZD1775 |
| up to time of surgery |
| D009373 |
| Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |