A Phase 0 Study of AZD1775 in Recurrent GBM Patients

NCT ID: NCT02207010

Last Updated: 2020-12-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

EARLY_PHASE1

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-07-31

Study Completion Date

2019-03-25

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Glioblastoma GBM

Keywords

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Glioblastoma GBM first recurrence

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

AZD1775

Intervention Type BIOLOGICAL

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

Interventions

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AZD1775

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

Intervention Type BIOLOGICAL

Other Intervention Names

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Wee1 inhibitor MK1775

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Ben & Catherine Ivy Foundation

OTHER

Sponsor Role collaborator

American Society of Clinical Oncology

OTHER

Sponsor Role collaborator

Barbara Ann Karmanos Cancer Institute

OTHER

Sponsor Role collaborator

Translational Genomics Research Institute

OTHER

Sponsor Role collaborator

St. Joseph's Hospital and Medical Center, Phoenix

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nader Sanai, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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

Phoenix, Arizona, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 29798906 (View on PubMed)

Other Identifiers

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BBTRC 001

Identifier Type: -

Identifier Source: org_study_id