Clinical trial NCT01547546: A Study of GDC-0084 in Patients With Progressive or Recurrent High-Grade Glioma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Glioblastoma, Glioma
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2012-03-08
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Safety: Incidence of adverse events
timeFrame: approximately 2 years
measure: Maximum tolerated dose (MTD)
timeFrame: approximately 1 year
Secondary outcomes:
measure: Pharmacokinetics: Area under the concentration-time curve
timeFrame: 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
measure: Best overall response rate, tumor assessments according to Response Assessment in Neuro-Oncology (RANO)
timeFrame: approximately 2 years
measure: Duration of response
timeFrame: approximately 2 years
measure: Progression-free survival
timeFrame: approximately 2 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Houston
country: United States
state: Texas
city: Barcelona
country: Spain
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Ellingson BM, Yao J, Raymond C, Nathanson DA, Chakhoyan A, Simpson J, Garner JS, Olivero AG, Mueller LU, Rodon J, Gerstner E, Cloughesy TF, Wen PY. Multiparametric MR-PET Imaging Predicts Pharmacokinetics and Clinical Response to GDC-0084 in Patients with Recurrent High-Grade Glioma. Clin Cancer Res. 2020 Jul 1;26(13):3135-3144. doi: 10.1158/1078-0432.CCR-19-3817. Epub 2020 Apr 8.
citation: Wen PY, Cloughesy TF, Olivero AG, Morrissey KM, Wilson TR, Lu X, Mueller LU, Coimbra AF, Ellingson BM, Gerstner E, Lee EQ, Rodon J. First-in-Human Phase I Study to Evaluate the Brain-Penetrant PI3K/mTOR Inhibitor GDC-0084 in Patients with Progressive or Recurrent High-Grade Glioma. Clin Cancer Res. 2020 Apr 15;26(8):1820-1828. doi: 10.1158/1078-0432.CCR-19-2808. Epub 2020 Jan 14.