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Glioblastoma, AdultPhase 2NCT03522298

Safety, Pharmacokinetics and Efficacy of Paxalisib (GDC-0084) in Newly-diagnosed Glioblastoma

A Phase 2 study testing Paxalisib (GDC-0084) in people with Glioblastoma, Adult, run by Kazia Therapeutics Limited at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioblastoma, Adult
What is being tested?
Paxalisib (GDC-0084)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
6 sitesUnited States
Study dates
15 May 2018to 30 Mar 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must meet all the following inclusion criteria to be eligible for enrollment into the study:
  • Age ≥ 18 years;
  • Life expectancy > 12 weeks;
  • Present with histologically confirmed intracranial (supratentorial) unmethylated MGMT promotor status GBM (WHO Grade lV astrocytoma) with a MGMT status that has been confirmed by validated PCR or validated alternate genomic analysis;
  • Have undergone maximal surgical resection of their tumor and within 6 weeks of surgery received initial treatment with XRT/TMZ which consisted of XRT by external beam to a partial brain field in daily fractions of 2.0 Gray (Gy), to a planned total dose to the tumor of 60.0 Gy, in conjunction with TMZ oral QD 75 mg/m2 in accordance with the Stupp regimen;
  • Must have measurable disease, according to RANO criteria for inclusion in the expansion cohort. Patients with non-measurable disease can be included in the dose-escalation cohorts;
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  • KPS ≥ 70;
  • Cranial magnetic resonance imaging (MRI) must have been performed within 7 days prior to or on the day of the Randomization/Week 1 Visit;
  • Stable or decreasing corticosteroid dose within 7 days prior to the first dose;
  • Adequate bone marrow/hematological function within 7 days prior to Day 1;
  • Adequate liver and renal function within 14 days prior to Day 1;
  • International normalized ratio (INR) or prothrombin time (PT) (secs) and activated partial thromboplastin time (aPTT) within 7 days prior to randomization:
  • Patients must be willing to forego other drug therapy against the tumor while enrolled in the study.

Who cannot join

  • Previous radiotherapy to the brain or cytotoxic drug therapy (including Gliadel® wafers) in addition to the required postoperative radiation plus TMZ, non-cytotoxic drug therapy, or experimental drug therapy directed against the brain tumor prior to this regimen, will be excluded. Patients may have received or be receiving corticosteroids, analgesics, and other drugs to treat symptoms or prevent complications but the dose must be stable at treatment start. NOTE: 5 aminolevulinic acid-mediated photodynamic therapy administered prior to surgery to aid in optimal surgical resection is not considered a chemotherapy agent;
  • Any prior or anticipated concomitant treatment involving a medical device (such as Optune®) applying tumor treating fields (TTF);
  • QT interval time of ≥ 470 msec;
  • Undetermined/indeterminate MGMT status;
  • Diabetic patients; prediabetic patients treated with metformin;
  • Use of any CYP3A4 inducing or inhibiting agents;
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  • Significant medical illnesses;
  • Women who are pregnant or who are lactating;
  • Diagnosed with infratentorial GBM, a tumor outside of brain or gliomatosis cerebri;
  • Evidence of recent hemorrhage on postoperative MRI of the brain;
  • Any previous malignancy; except for adequately controlled limited basal cell carcinoma of the skin, squamous carcinoma of the skin or carcinoma in situ of the cervix, or one which has been absent for ≥3 years;

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites
  • University of Colorado Cancer Center

    Aurora, Colorado, 80045

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • John Theurer Cancer Center at Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of California Los Angeles - Jonsson Comprehensive Cancer Center

    Los Angeles, California, 90095

  • University of Oklahoma Health Sciences Center (Stephenson Cancer Center)

    Oklahoma City, Oklahoma, 73104

Other trials in United States

About this study

Official title: 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

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).

Read the 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 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.

Being tested
Paxalisib (GDC-0084)
Keywords
newly diagnosed, unmethylated O6 methylguanine-methyltransferase (MGMT) promoter status
Medical subject headings
Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Paxalisib (GDC-0084)Drug

    Patients will be dosed orally with paxalisib (GDC-0084) capsules (15-mg each) at the dose and schedule to which they are assigned.

Study groups in NCT03522298
Study groupRoleWhat they receive
Dose Escalation and Expansion CohortsExperimentalThis 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.
Receives: Drug: Paxalisib (GDC-0084)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

    A DLT was defined as a Grade 3 or 4 toxicity occurring within the DLT assessment window and assessed to be probably or possibly related to paxalisib. DLTs were graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. CTCAE Grade 3 is a severe adverse event (AE) and Grade 4 is a life-threatening or disabling AE. DLTs were collected to determine the maximum tolerated dose (MTD), which was defined as the dose level below the dose at which less than 33% of participants experienced a DLT.

    Measured: Cycle 1, Days 1-28

Secondary outcomes (7)
  1. Incidence of Treatment-emergent Adverse Events (TEAEs)

    The toxicity assessments were made according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. A TEAE is any AE occurring or worsening on/after the first study drug dose and within 28 days after the last dose date. The number of participants with Grade 1 to 5 TEAEs are reported here. Specific Adverse Event terms are provided in the Adverse Event module

    Measured: 24 months

  2. Incidence of Serious Adverse Events (SAEs)

    An SAE is any AE that meets one or more of the following: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; requires intervention to prevent permanent impairment or damage. Specific AE terms are provided in the Adverse Event module

    Measured: 24 months

  3. Incidence of Treatment-emergent Grade 3/4 Treatment Emergent Adverse Events

    Treatment emergent Adverse Events were graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. CTCAE Grade 3 is a severe adverse event (AE) and Grade 4 is a life-threatening or disabling AE. Participants are counted at the highest grade TEAE that they experienced.

    Measured: 24 months

  4. Number of Participants Who Experienced a Change in Electrocardiogram (ECG) Parameter QTc

    A change in ECG parameter QTc was defined as an increase of QTc to a value ≥ 500 msec or a change from baseline of at least 60 msec.

    Measured: 24 months

  5. Number of Participants Who Experienced a Change Left Ventricular Ejection Fraction

    A change in left ventricular ejection fraction (LVEF) was defined as a reduction in LVEF to a value of ≤ 45% from baseline.

    Measured: 24 months

  6. Progression-free Survival Interval Using Using mRANO Criteria/Investigator Review.

    Progression-free survival is defined as the duration of time from start of treatment to time of progression or death, whichever comes first.

    Measured: 24 months

  7. Overall Survival Using RANO Criteria.

    Overall survival is defined as the duration of time from the first day of study treatment until the date of death.

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 May 2018
  2. Study start15 May 2018
  3. Primary completion30 Mar 2023
  4. Study completion30 Mar 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
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)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03522298
Sponsor's protocol ID
NVGN-0084-201
Status last verified
Mar 2025
First submitted
20 Mar 2018
Last updated
24 Mar 2025
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Paxalisib (GDC-0084) in people with Glioblastoma, Adult, run by Kazia Therapeutics Limited at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) (time frame: Cycle 1, Days 1-28). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2025.

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