Safety, Pharmacokinetics and Efficacy of GDC-0084 in Newly-diagnosed Glioblastoma Multiforme
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|ClinicalTrials.gov Identifier: NCT03522298|
Recruitment Status : Recruiting
First Posted : May 11, 2018
Last Update Posted : September 13, 2018
This protocol has a 2-part design:
The phase 2a study component is an open-label, multicenter, phase 2a dose-escalation and expansion study to assess the safety, tolerability, recommended phase 2 dose (RP2D), pharmacokinetics (PK) and clinical activity of GDC-0084 in patients with newly-diagnosed glioblastoma multiforme (GBM) with unmethylated MGMT promoter status as adjuvant therapy following surgical resection and initial chemoradiation with temozolomide (TMZ). The phase 2a study is fully detailed in this submission.
The phase 2b study component comprises an evaluation of clinical activity of GDC-0084 compared to TMZ in as adjuvant therapy following surgical resection and initial chemoradiation with TMZ and will be initiated following the determination of RP2D in the phase 2a study (Part 1). The phase 2b component will be will be further detailed in an amendment to this submission.
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma, Adult||Drug: GDC-0084||Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||66 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||The phase 2a study comprises an open-label, multicenter, phase 2a dose-escalation and expansion study to assess the safety, tolerability, RP2D, PK and clinical activity of GDC 0084 in patients with newly-diagnosed GBM with unmethylated MGMT promoter status as adjuvant therapy following surgical resection and initial chemoradiation with TMZ.|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of the PI3K/mTOR Inhibitor GDC-0084 Administered to Patients With Glioblastoma Multiforme Characterized by Unmethylated O6-methylguanine-methyltransferase Promoter Status Following Surgical Resection and Standard Concomitant Chemoradiation Therapy With Temozolomide|
|Actual Study Start Date :||May 15, 2018|
|Estimated Primary Completion Date :||March 30, 2020|
|Estimated Study Completion Date :||December 30, 2020|
Experimental: Dose Escalation and Expansion Cohorts
This is an open-label study.
Patients in Stage 1 will be enrolled and sequentially assigned to a dose cohort.
The initial cohort will receive an oral dose of 60 mg GDC-0084 QD (4 x 15 mg capsules). Patients of future dose cohorts will receive GDC-0084 at increasing levels with 15 mg steps until a dose-limiting toxicity occurs (DLT) occurs. The dose level where <1/3 of the patients exhibit a DLT will be determined the Maximum Tolerated Dose (MTD).
Dose escalation will occur for three separate dose schedules including QD, every other day (QOD) and 3 times a week on consecutive days (3 days on/4 days off), i.e. an MTD will be established for three different dose schedules.
In stage 2, the expansion phase, patients will receive doses of oral GDC-0084 at the MTD established for each of the three dosing schedules until disease progression or an unacceptable toxicity, whichever occurs first.
Patients will be randomized in a 1:1:1 ratio to one of the three dose schedules.
Patients will be dosed orally with GDC-0084 capsules (15-mg each) at the dose and schedule to which they are assigned.
- Dose limiting toxicities (DLTs) [ Time Frame: 12 months ]The recommended Phase 2 dose and schedule. DLTs according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03.
- Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: 24 months ]TEAEs defined as any AE occurring or worsening on/after the first study drug dose and within 28 days after the last dose date. AEs will be coded according to the Medical Dictionary for Regulatory Activities (MedDRA).
- Incidence of serious adverse events (SAEs) [ Time Frame: 24 months ]AEs will be coded according to the Medical Dictionary for Regulatory Activities (MedDRA).
- Incidence of treatment-emergent Grade 3/4 clinical laboratory abnormalities. [ Time Frame: 24 months ]Clinical laboratory values will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03, for applicable tests.
- Change in electrocardiogram (ECG) parameter QTc. [ Time Frame: 24 months ]The number and percentage of patients with an increase of QTc to a value ≥ 500 msec or a change from baseline of at least 60 msec will be presented overall and by visit.
- Change in left ventricular ejection fraction (LVEF). [ Time Frame: 24 months ]The number and percentage of patients with a drop in LVEF to a value of ≤ 45% from baseline will be presented overall and by visit.
- Progression-free survival interval using RANO Criteria. [ Time Frame: 24 months ]
- Overall survival using RANO Criteria. [ Time Frame: 24 months ]
- Pharmacokinetics of GDC-0084 as area under the curve from time 0 to last measurable time point (AUC0-last) and/or area under the curve from time 0 to infinity (AUC0-inf). [ Time Frame: 24 months ]
- Pharmacokinetics of GDC-0084 as maximum (Cmax) and minimum concentration (Cmin). [ Time Frame: 24 months ]
- Pharmacokinetics of GDC-0084 as time to reach Cmax (Tmax). [ Time Frame: 24 months ]
- Pharmacokinetics of GDC-0084 as half-life. [ Time Frame: 24 months ]
- Change in FDG-PET uptake in tumor and normal brain tissue in response to GDC-0084 in patients with measurable disease. [ Time Frame: 24 months ]
- Disease control rate measured as the proportion of patients achieving a confirmed best overall response (BOR) of complete response (CR), partial response (PR), or stable disease (SD) according to RANO criteria. [ Time Frame: 24 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03522298
|Contact: Jeremy Simpson, PhD||+612 9472 email@example.com|
|Contact: James Garner, MD||+612 9472 firstname.lastname@example.org|
|United States, California|
|University of California Los Angeles - Jonsson Comprehensive Cancer Center||Recruiting|
|Los Angeles, California, United States, 90095|
|Contact: Emese Filka email@example.com|
|Principal Investigator: Timothy Cloughesy, MD|
|United States, Colorado|
|University of Colorado Cancer Center||Recruiting|
|Aurora, Colorado, United States, 80045|
|Contact: Rachel Freedman Rachel.Freedman@ucdenver.edu|
|Principal Investigator: Denise Damek, MD|
|United States, Massachusetts|
|Dana Farber Cancer Institute||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Swati Samtani Swati_Samtani@dfci.harvard.edu|
|Principal Investigator: Patrick Wen, MD|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Edwin Nunez Enunez2@mgh.harvard.edu|
|Principal Investigator: Elizabeth Gerstner, MD|
|United States, New Jersey|
|John Theurer Cancer Center at Hackensack University Medical Center||Recruiting|
|Hackensack, New Jersey, United States, 07601|
|Contact: Lori Cappello 551-996-5098 Lori.Cappello@HackensackMeridian.org|
|Principal Investigator: Samual A Goldlust, MD|
|United States, Oklahoma|
|University of Oklahoma Health Sciences Center (Stephenson Cancer Center)||Recruiting|
|Oklahoma City, Oklahoma, United States, 73104|
|Contact: Julie Schreiner|
|Principal Investigator: James Battiste, MD|
|United States, Texas|
|MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Kathy Hunter 713-745-5769 firstname.lastname@example.org|
|Principal Investigator: John de Groot, MD|
|Study Director:||James Garner, MD||Kazia Therapeutics Limited|