Safety, Pharmacokinetics and Efficacy of Paxalisib (GDC-0084) in Newly-diagnosed Glioblastoma
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ClinicalTrials.gov Identifier: NCT03522298 |
Recruitment Status :
Completed
First Posted : May 11, 2018
Last Update Posted : March 15, 2024
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Tracking Information | |||||
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First Submitted Date ICMJE | March 20, 2018 | ||||
First Posted Date ICMJE | May 11, 2018 | ||||
Last Update Posted Date | March 15, 2024 | ||||
Actual Study Start Date ICMJE | May 15, 2018 | ||||
Actual Primary Completion Date | March 30, 2023 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
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.
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Original Primary Outcome Measures ICMJE | Same as current | ||||
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Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures |
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Original Other Pre-specified Outcome Measures |
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Descriptive Information | |||||
Brief Title ICMJE | Safety, Pharmacokinetics and Efficacy of Paxalisib (GDC-0084) in Newly-diagnosed Glioblastoma | ||||
Official Title ICMJE | A Phase 2 Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of the PI3K/mTOR Inhibitor Paxalisib (GDC-0084) Administered to Patients With Glioblastoma Characterized by Unmethylated O6-methylguanine-methyltransferase Promoter Status Following Surgical Resection and Standard Concomitant Chemoradiation Therapy With Temozolomide | ||||
Brief Summary | This protocol has a 2-part design: This phase 2 study is an open-label, multicenter, dose-escalation and expansion study to assess the safety, tolerability, recommended phase 2 dose (RP2D), pharmacokinetics (PK) and clinical activity of paxalisib in patients with newly-diagnosed glioblastoma (GBM) with unmethylated MGMT promoter status as adjuvant therapy following surgical resection and initial chemoradiation with temozolomide (TMZ). |
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Detailed Description | Stage 1 Dose-Escalation and Maximum Tolerated Dose The dose-escalation portion of the study (Stage 1) will use a standard "3 + 3" design to determine the MTD for QD dosing. Approximately 6 - 12 patients with newly diagnosed GBM will be enrolled in Stage 1. The MTD for QD dosing will be determined. The initial dose level for QD dosing will be 60 mg (Dose Level 0). This dose is based on the phase 1 findings outlined in the rationale in the protocol, adding 1 dose level to test for a potential MTD increase. Dose-escalation will occur in Stage 1:
Decisions regarding dose-escalation and selection will be made by a Cohort Review Committee (CRC). All AEs, including DLTs, will be reported, with severity assessed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. After determination of the MTD, patients continue to receive their protocol-assigned dose levels of paxalisib until progression of their disease or an unacceptable toxicity, whichever occurs first. Stage 2 Expansion stage (2) of the study will be a two-arm, randomized, open-label expansion study to further characterize the safety, tolerability and PK of paxalisib as well as to provide a preliminary assessment of single-agent activity of paxalisib in patients with GBM. Approximately 20 patients will be enrolled in the expansion cohort in 2 treatment arms (10 per am) to examine the PK of paxalisib in fed and fasted-conditions, according to the defined study eligibility criteria. Stage 2 of the study will be initiated with recruitment of new patients as soon as the MTD has been determined. Patients enrolled in Stage 2 may continue the study at the dose allocated until disease progression or unacceptable toxicity. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 2 | ||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Intervention Model Description: This phase 2 study comprises an open-label, multicenter, dose-escalation and expansion study to assess the safety, tolerability, RP2D, PK and clinical activity of paxalisib 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)Primary Purpose: Treatment |
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Condition ICMJE | Glioblastoma, Adult | ||||
Intervention ICMJE | Drug: Paxalisib (GDC-0084)
Patients will be dosed orally with paxalisib (GDC-0084) capsules (15-mg each) at the dose and schedule to which they are assigned.
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Study Arms ICMJE | 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 paxalisib QD (4 x 15 mg capsules). Patients of future dose cohorts will receive paxalisib 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). In stage 1, dose escalation will occur for QD dosing. In stage 2, the expansion phase, patients will receive doses of oral paxalisib at the MTD in stage 1, until disease progression or an unacceptable toxicity, whichever occurs first. Patients will be randomized in a 1:1 ratio to fed or fasted schedules. Intervention: Drug: Paxalisib (GDC-0084)
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Completed | ||||
Actual Enrollment ICMJE |
30 | ||||
Original Estimated Enrollment ICMJE |
66 | ||||
Actual Study Completion Date ICMJE | March 30, 2023 | ||||
Actual Primary Completion Date | March 30, 2023 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Inclusion Criteria: Patients must meet all the following inclusion criteria to be eligible for enrollment into the study:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
Listed Location Countries ICMJE | United States | ||||
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Administrative Information | |||||
NCT Number ICMJE | NCT03522298 | ||||
Other Study ID Numbers ICMJE | NVGN-0084-201 | ||||
Has Data Monitoring Committee | Not Provided | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | Kazia Therapeutics Limited | ||||
Original Responsible Party | Same as current | ||||
Current Study Sponsor ICMJE | Kazia Therapeutics Limited | ||||
Original Study Sponsor ICMJE | Same as current | ||||
Collaborators ICMJE | Not Provided | ||||
Investigators ICMJE |
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PRS Account | Kazia Therapeutics Limited | ||||
Verification Date | March 2024 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |