A Phase 0 Study of AZD1775 in Recurrent GBM Patients

NCT02207010 | Completed Early Phase 1 DMC

• 1 other identifier: BBTRC 001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Glioblastoma; GBM

Keywords

Glioblastoma; GBM; first recurrence

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (3)

• Degree of CDC2 (Tyr15) phosphorylation in tissue

  at baseline and up to 26 hours post dosing

• Number of GBM cells in M-phase of cell cycle (PH3)

  at baseline and up to 26 hours post dose AZD1775

• Presence of double-strand DNA damage (γH2AX).

  at baseline and up to 26 hours post dose AZD1775

Other Outcomes (2)

• P53 mutation status

  up to time of surgery

• Presence of checkpoint regulator genes in GBM specimens

  up to time of surgery

Study Arms (1)

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

Biological: AZD1775

Interventions

AZD1775 BIOLOGICAL

All patients receive a single dose of the oral study drug prior to surgery for resection of GBM.

Also known as: Wee1 inhibitor, MK1775

AZD1775

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• Less than 18 years of age
• Diagnosis of anything other than first-recurrence GBM
• GBM tissue from first-resection not available
• Previous treatment with AZD1775
• 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
• Patient has known hypersensitivity to the components of potential study therapy or its analogs.
• 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.
• 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.
• Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• 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.
• Patients expecting to reproduce within the projected duration of the study (estimated to be 1 year), and women who are pregnant or breastfeeding.
• Patient is known to be suffering from Acquired Immune Deficiency Syndrome (AIDS).
• Patient has known history of Hepatitis B or C.
• Patient has symptomatic ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions is eligible.
• Patient has a clinical history suggestive of Li-Fraumeni Syndrome.

Sponsors & Collaborators

• St. Joseph's Hospital and Medical Center, Phoenix: lead
• The Ben & Catherine Ivy Foundation: collaborator
• American Society of Clinical Oncology: collaborator
• Barbara Ann Karmanos Cancer Institute: collaborator
• Translational Genomics Research Institute: collaborator

Study Sites (1)

Barrow Neurological Institute at St. Joseph's Hospital Medical Center

Phoenix, Arizona, 85013, United States

Location

Related Publications (1)

• 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.

  PMID: 29798906 DERIVED

MeSH Terms

Conditions

Glioblastoma

Interventions

adavosertib

Condition Hierarchy (Ancestors)

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

Study Officials

• Nader Sanai, MD

  Barrow Neurological Institute at St.Joseph's Hospital Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2014
• First Posted: August 1, 2014
• Study Start: July 1, 2014
• Primary Completion: December 31, 2015
• Study Completion: March 25, 2019
• Last Updated: December 10, 2020

Record last verified: 2020-12

Locations

US (1)