Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

A Phase 0 Study of AZD1775 in Recurrent GBM Patients

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.
 
ClinicalTrials.gov Identifier: NCT02207010
Recruitment Status : Unknown
Verified January 2017 by St. Joseph's Hospital and Medical Center, Phoenix.
Recruitment status was:  Active, not recruiting
First Posted : August 1, 2014
Last Update Posted : January 6, 2017
Sponsor:
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

Tracking Information
First Submitted Date  ICMJE July 28, 2014
First Posted Date  ICMJE August 1, 2014
Last Update Posted Date January 6, 2017
Study Start Date  ICMJE July 2014
Estimated Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 30, 2014)
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02207010 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 30, 2014)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: July 30, 2014)
  • 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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE A Phase 0 Study of AZD1775 in Recurrent GBM Patients
Official Title  ICMJE A Phase 0 Study of AZD1775 in Preoperative Glioblastoma Multiforme (GBM) Patients Scheduled for Resection to Evaluate for Central Nervous System (CNS) Penetration
Brief Summary

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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Condition  ICMJE
  • Glioblastoma
  • GBM
Intervention  ICMJE 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
Study Arms  ICMJE 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
Intervention: Biological: AZD1775
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Actual Enrollment  ICMJE
 (submitted: March 16, 2016)
20
Original Estimated Enrollment  ICMJE
 (submitted: July 30, 2014)
40
Estimated Study Completion Date  ICMJE May 2018
Estimated Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02207010
Other Study ID Numbers  ICMJE BBTRC 001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party St. Joseph's Hospital and Medical Center, Phoenix
Study Sponsor  ICMJE St. Joseph's Hospital and Medical Center, Phoenix
Collaborators  ICMJE
  • The Ben & Catherine Ivy Foundation
  • American Society of Clinical Oncology
  • Barbara Ann Karmanos Cancer Institute
  • Translational Genomics Research Institute
Investigators  ICMJE
Principal Investigator: Nader Sanai, MD Barrow Neurological Institute at St.Joseph's Hospital Medical Center
PRS Account St. Joseph's Hospital and Medical Center, Phoenix
Verification Date January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP