A Study of GDC-0084 in Patients With Progressive or Recurrent High-Grade Glioma

Study Overview
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Brief Summary
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This open-label, multicenter, Phase I, dose-escalating study will evaluate the safety and tolerability, pharmacokinetics, pharmacodynamics and efficacy of GDC-0084 in patients with progressive or recurrent high-grade glioma. Stage 1 is the dose escalation part of the study. Stage 2, patients will receive GDC-0084 at a recommended dose for future studies.

Official Title
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An Open-label, Phase I, Dose-escalation Study Evaluating the Safety and Tolerability of GDC-0084 Administered to Patients With Progressive or Recurrent High-grade Glioma

Conditions
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Glioblastoma, Glioma

Intervention / Treatment
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* Drug: GDC-0084


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, >/= 18 years of age Interval of at least 12 weeks from completion of adjuvant radiotherapy for gliomas to study entry Karnofsky Performance Status of >/= 70 at screening Confirmed measurable disease per RANO Adequate hematologic and organ function Patients enrolled in Stage 1: Histologically documented recurrent or progressive high-grade gliomas (WHO Grade III-IV) Prior treatment with at least one regimen for gliomas (radiotherapy with or without chemotherapy for Grade III gliomas and radiotherapy with chemotherapy for Grade IV gliomas) and/or not considered to be a candidate for regimens known to provide clinical benefit Patients enrolled in Stage 2: Histologically documented recurrent or progressive glioblastoma (WHO Grade IV gliomas) Prior treatment with one or two regimens for glioblastoma (with the initial regimen consisting of radiotherapy with chemotherapy) Exclusion Criteria: Treatment with anti-tumor therapy (approved or experimental) within 4 weeks prior to initiation of study drug Requirement for anticoagulants such as warfarin or any other warfarin-derivative anticoagulants; low-molecular-weight heparin is permitted Any contraindication to MRI examination Evidence of Grade >/= 1 intracranial hemorrhage Active congestive heart failure or ventricular arrhythmia requiring medication Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse or cirrhosis Unresolved toxicity from prior therapy with the exception of lymphopenia (for patients with prior temozolomide) and alopecia Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br> | Drug: GDC-0084<br>* Multiple doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Incidence of adverse events |  | approximately 2 years | 
| Maximum tolerated dose (MTD) |  | approximately 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Area under the concentration-time curve |  | Pre- and post-dose Days 1, 8, 15, 22 and 29 Cycle 1, Day 1 every following Cycle until 30 days after the last dose of study drug | 
| Best overall response rate, tumor assessments according to Response Assessment in Neuro-Oncology (RANO) |  | approximately 2 years | 
| Duration of response |  | approximately 2 years | 
| Progression-free survival |  | approximately 2 years |