Ignite Creation Date:
2024-05-06 @ 11:28 AM
Last Modification Date:
2024-10-26 @ 12:45 PM
Study NCT ID:
NCT03522298
Status:
COMPLETED
Last Update Posted:
2024-03-15
First Post:
2018-03-20
Brief Title:
Safety Pharmacokinetics and Efficacy of Paxalisib GDC-0084 in Newly-diagnosed Glioblastoma
Sponsor:
Kazia Therapeutics Limited
Organization:
Kazia Therapeutics Limited
Study Overview
Official Title:
A Phase 2 Study to Evaluate the Safety Pharmacokinetics and Efficacy of the PI3KmTOR 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
Status:
COMPLETED
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
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
The initial dose Dose Level 0 for QD MTD determination in Step 1 will be 60 mg Dose levels will increase in 15 mg steps
The dose-escalation portion of the study Stage 1 will use a standard 3 3 design to assess the safety tolerability and PK of paxalisib administered orally in 28-day cycles
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 403
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
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
The initial dose Dose Level 0 for QD MTD determination in Step 1 will be 60 mg Dose levels will increase in 15 mg steps
The dose-escalation portion of the study Stage 1 will use a standard 3 3 design to assess the safety tolerability and PK of paxalisib administered orally in 28-day cycles
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 403
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None