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

Phase 1
Completed
Conditions
Glioblastoma, Glioma
Interventions
Registration Number
NCT01547546
Lead Sponsor
Genentech, Inc.
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
29
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Single ArmGDC-0084-
Primary Outcome Measures
NameTimeMethod
Maximum tolerated dose (MTD)approximately 1 year
Safety: Incidence of adverse eventsapproximately 2 years
Secondary Outcome Measures
NameTimeMethod
Duration of responseapproximately 2 years
Pharmacokinetics: Area under the concentration-time curvePre- 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
Progression-free survivalapproximately 2 years
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