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A Phase 0 Study of AZD1775 in Recurrent GBM Patients

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02207010
First Posted: August 1, 2014
Last Update Posted: January 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
The Ben & Catherine Ivy Foundation
American Society of Clinical Oncology
Barbara Ann Karmanos Cancer Institute
Translational Genomics Research Institute
Information provided by (Responsible Party):
St. Joseph's Hospital and Medical Center, Phoenix
  Purpose

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.


Condition Intervention Phase
Glioblastoma GBM Biological: AZD1775 Early Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Official Title: A Phase 0 Study of AZD1775 in Preoperative Glioblastoma Multiforme (GBM) Patients Scheduled for Resection to Evaluate for Central Nervous System (CNS) Penetration

Resource links provided by NLM:


Further study details as provided by St. Joseph's Hospital and Medical Center, Phoenix:

Primary Outcome Measures:
  • Plasma concentration of AZD1775 following single dose of AZD1775 [ Time Frame: at baseline, 2-4, 8-12, and 22-26 hours following single dose of AZD1775 ]
    Will be summarized using descriptive statistics

  • Intratumoral concentration of AZD1775 [ Time Frame: up to day of surgery ]
    Will be summarized using descriptive statistics


Secondary Outcome Measures:
  • Degree of CDC2 (Tyr15) phosphorylation in tissue [ Time Frame: at baseline and up to 26 hours post dosing ]
    Will be summarized using descriptive statistics

  • Number of GBM cells in M-phase of cell cycle (PH3) [ Time Frame: at baseline and up to 26 hours post dose AZD1775 ]
    Will be summarized using descriptive statistics

  • Presence of double-strand DNA damage (γH2AX). [ Time Frame: at baseline and up to 26 hours post dose AZD1775 ]
    Will be summarized using descriptive statistics


Other Outcome Measures:
  • P53 mutation status [ Time Frame: up to time of surgery ]
    Will be summarized using descriptive statistics

  • Presence of checkpoint regulator genes in GBM specimens [ Time Frame: up to time of surgery ]
    checkpoint regulator genes in GBM specimens


Enrollment: 20
Study Start Date: July 2014
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AZD1775
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
Biological: AZD1775
All patients receive a single dose of the oral study drug prior to surgery for resection of GBM.
Other Names:
  • Wee1 inhibitor
  • MK1775

Detailed Description:

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with 1 prior resection of histologically-diagnosed de novo GBM
  2. Patient must have MRI evidence of disease recurrence
  3. Patients must have Eastern Cooperative Oncology Group (ECOG) performance status ≤2
  4. Patients ≥ 18 years of age
  5. Adequate hematologic, renal, and hepatic function
  6. Patients must not have co-morbid condition(s) that, at the opinion of the investigator, prevent safe surgical treatment
  7. Patients must not have active infection or fever > 38.5°C
  8. Patients must not be pregnant or nursing
  9. Patients must have archival tumor tissue block available for research use
  10. Ability to understand and the willingness to sign a written informed consent document.
  11. Patient has voluntarily agreed to participate by giving written informed consent.

Exclusion Criteria:

  1. Less than 18 years of age
  2. Diagnosis of anything other than first-recurrence GBM
  3. GBM tissue from first-resection not available
  4. Previous treatment with AZD1775
  5. Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  6. Patient has known hypersensitivity to the components of potential study therapy or its analogs.
  7. Patient has had prescription or non-prescription drugs or other products known to be metabolized by cytochrome P450 3A4 (CYP3A4), or to inhibit or induce CYP3A4, which cannot be discontinued prior to Day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study medication (inhibitors generally for 5 half-lives). Medications of particular concern are the following inhibitors of CYP3A4: azole antifungals (ketoconazole itraconazole, fluconazole and voriconazole), macrolide antibiotics (erythromycin, clarithromycin), cimetidine, HIV protease inhibitors, nefazodone and the following inducers of CYP3A4: phenytoin, barbiturates and rifampicin. Substrates of CYP3A4 include statins (lovastatin, simvastatin), midazolam, terfenadine, astemizole, and cisapride. CYP3A4.
  8. Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate.
  9. Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  10. Patient is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse.
  11. Patients expecting to reproduce within the projected duration of the study (estimated to be 1 year), and women who are pregnant or breastfeeding.
  12. Patient is known to be suffering from Acquired Immune Deficiency Syndrome (AIDS).
  13. Patient has known history of Hepatitis B or C.
  14. Patient has symptomatic ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions is eligible.
  15. Patient has a clinical history suggestive of Li-Fraumeni Syndrome.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02207010


Locations
United States, Arizona
Barrow Neurological Institute at St. Joseph's Hospital Medical Center
Phoenix, Arizona, United States, 85013
Sponsors and Collaborators
St. Joseph's Hospital and Medical Center, Phoenix
The Ben & Catherine Ivy Foundation
American Society of Clinical Oncology
Barbara Ann Karmanos Cancer Institute
Translational Genomics Research Institute
Investigators
Principal Investigator: Nader Sanai, MD Barrow Neurological Institute at St.Joseph's Hospital Medical Center
  More Information

Responsible Party: St. Joseph's Hospital and Medical Center, Phoenix
ClinicalTrials.gov Identifier: NCT02207010     History of Changes
Other Study ID Numbers: BBTRC 001
First Submitted: July 28, 2014
First Posted: August 1, 2014
Last Update Posted: January 6, 2017
Last Verified: January 2017

Keywords provided by St. Joseph's Hospital and Medical Center, Phoenix:
Glioblastoma
GBM
first recurrence

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue