GlioblastomaPhase 2NCT05183204
Paxalisib With a High Fat, Low Carb Diet and Metformin for Glioblastoma
A Phase 2 study testing Paxalisib, Metformin and Ketogenic Diet in people with Glioblastoma, run by Weill Medical College of Cornell University at 1 site in United States.
Trial summary
This study is for patients with newly diagnosed glioblastoma, as well as patients who have recurring glioblastoma. Subjects will be given daily paxalisib and metformin while also maintaining a ketogenic diet. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Paxalisib, Metformin and Ketogenic Diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Feb 2022to 10 Aug 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Histologically-confirmed, on initial diagnosis and/or at the time of recurrence, glioblastoma (WHO Grade IV glioma); tumors situated primarily in the infratentorial compartment will be excluded.
- Radiologically-confirmed disease progression at a minimum of three months after completion of chemoradiotherapy.
- Having previously been treated with definitive fractionated radiation consistent with NCCN guidelines for radiotherapy of GBM.
- Any MGMT promoter methylation status is acceptable.
- Patients of any gender, with age ≥ 18 years at the time of randomization.
- Written, signed, and dated informed consent to participate in this study, in a format approved by each site's Institutional Review Board (IRB).
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- Life expectancy > 12 weeks in the judgment of the investigator.
- Karnofsky Performance Status (KPS) ≥ 70.
- If receiving dexamethasone, dose is < 4mg daily
- No history of allergy or other intolerance to metformin.
- Adequate organ and bone marrow function at the time of screening, including
- White blood cell count (WBC) > 3,000/µL;
- absolute neutrophil count > 1,500/mm3
- Platelet count of > 100,000/mm3;
- Hemoglobin > 10 mg/dL (post-transfusion allowed)
- Total bilirubin ≤ 1.5 x ULN
- AST and ALT ≤ 2.5 x ULN
- Serum glucose < 140 mg/dL
- Urine dipstick for proteinuria < 2+. Patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis should undergo a 24-hour urine collection and must demonstrate ≤ 1.0 g of protein in 24 hours, OR Urine protein/creatinine ratio ≤ 1.
- Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply:
- They have recovered from the effects of surgery
- Residual disease following resection of recurrent tumor is not mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, a MRI should be done:
- No later than 96 hours in the immediate post-operative period OR ii. At least 4 weeks post-operatively In both cases, they also need to have it within 21 days of registration and be on a steroid dosage (<4mg of dex) that has been stable for at least 5 days before registration on a steroid dosage that has been stable for at least 5 days. If the steroid dose is increased (but not if its decreased) between the date of imaging and registration, a new baseline MRI is required on a stable steroid dosage for at least 5 days
- The effects of paxalisib on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (e.g., hormonal or barrier method of birth control) prior to study entry, for the duration of study participation and for a three-month period (90 days) afterwards in an abundance of caution. Female subjects will be required to demonstrate a negative urine pregnancy test prior to study entry and subjects who are lactating should be excluded.
- Able and willing, in the judgment of the investigator, to meet all protocol-required treatments, investigations and visits. This must include the ability for the subject to comply with daily self-administration of an oral therapy, or reliable means for treatment to be administered by a dependable third party such as a relative or caregiver. In addition, subjects must be willing and able to comply with the requirements of a ketogenic diet. Subjects must also be able and willing to undergo cranial magnetic resonance imaging and positron-emission tomography, and to receive gadolinium-containing contrast agent.
Who cannot join
- Patients with tumors exhibiting mutated isocitrate dehydrogenase-1 or 2 (IDH-1, 2).
- Patients receiving prior treatment with bevacizumab, other PI3K inhibitors or inhibitors of the PI3K pathway (e.g. mTOR inhibitors).
- Patients currently are during the course of their illness on a ketogenic diet for more than 2 weeks.
- Patients with type 1 diabetes or poorly controlled type 2 diabetes with A1C > 7.5%.
- QT interval of ≥ 450 msec.
- Any ongoing malignancy requiring treatment currently or expected to require treatment in the next 12 months.
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- Any pre-existing or inter-current illness or pathology which, in the judgment of the investigator, has the potential to increase the safety risk associated with paxalisib administration, or to confound the results of the study.
- Patients receiving any medications or substances that are moderate and/or potent enzyme inducers or inhibitors which may have an effect on the metabolism of paxalisib (e.g. Nystatin swish and swallow, rather than Fluconazole, will be used for oral candidiasis).
- Known hypersensitivity or intolerance to paxalisib or metformin.
- Patients unable to undergo an MRI scan.
- History of bariatric surgery.
- History of severe nephrolithiasis requiring urologic intervention.
- History of severe pancreatitis or pancreatic exocrine insufficiency.
- History of primary hypertriglyceridemia (Familial chylomicronemia, familial hypertriglyceridemia, or familial dysbetalipoproteinemia).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2 Trial of Paxalisib Combined With a Ketogenic Diet and Metformin for Newly Diagnosed and Recurrent Glioblastoma
This study is for patients with newly diagnosed glioblastoma, as well as patients who have recurring glioblastoma. Subjects will be given daily paxalisib and metformin while also maintaining a ketogenic diet.
The purpose of this study is to assess the safety of Paxalisib while maintaining a ketogenic diet (a high fat, low carbohydrate diet) and Metformin (a drug approved by the Food and Drug Administration to treat type 2 diabetes), and to see what effects it has on glioblastoma.
Read the detailed description
This is a two stage, two cohort phase 2 trial of a new blood-brain penetrant PI3K/mTOR inhibitor (paxalisib) combined with a ketogenic diet plus metformin in patients with either newly diagnosed MGMT unmethylated glioblastoma or patients with recurrent glioblastoma regardless of MGMT promoter methylation status.
- Conditions
- Glioblastoma
- Being tested
- Paxalisib, Metformin, Ketogenic Diet
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaxalisibDrug
Patients will receive paxalisib starting at a dose of 45 mg/day. If well tolerated after 28 days, the dose of paxalisib will be increased to 60 mg/day.
MetforminDrug
Patients will receive metformin on Cycle 1, Day 1 at a starting dose of 850 mg QD, and if tolerated, will be increased to 850 mg BID on Cycle 2, Day 1 (1700 mg/day). If that dose is tolerated, metformin will be increased to 850 mg TID (2550 mg/day) beginning on Cycle 3, Day 1.
Ketogenic DietOther
The ketogenic diet is high-fat, low carbohydrate diet. Ketogenic diet will be maintained on a continuous basis starting on Cycle 1, Day 1 and continuing throughout the trial.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Newly diagnosed MGMT unmethylated glioblastoma | Experimental | Not described Receives: Drug: Paxalisib; Drug: Metformin; Other: Ketogenic Diet |
| Arm 2: Recurrent glioblastoma, regardless of methylation status | Experimental | Not described Receives: Drug: Paxalisib; Drug: Metformin; Other: Ketogenic Diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival, defined as the survival rate at 6 months
Measured by the occurrence of a progression event as per RANO criteria or death due to any cause prior to 6 months
Measured: At 6 months after the start of study treatment
Secondary outcomes (3)
Overall survival, defined as the time of first study treatment to death from any cause
Measured: From the start of study enrollment until death, up to approximately 18 months
Change in insulin levels
Evaluated by the mean and standard deviation of values over time
Measured: From baseline assessments through 8 weeks post-treatment
Change in tumor glucose uptake values
Measured by FDG-PET/DCE MRI
Measured: From baseline assessments through 8 weeks post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2022
- Study start14 Feb 2022
- Primary completion10 Aug 2026
- Study completion10 Aug 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- Kazia Therapeutics Limited
- Responsible party
- Sponsor
- Investigators
- Howard Fine, MD, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05183204
- Sponsor's protocol ID
- 21-05023537
- Status last verified
- Sep 2026
- First submitted
- 20 Dec 2021
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Trial of Paxalisib Combined With a Ketogenic Diet and Metformin for Newly Diagnosed and Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT05183204
- Acronym / sponsor ID
- 21-05023537
- Conditions
- Glioblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- Kazia Therapeutics Limited
- Study start
- 14 Feb 2022 (actual)
- Primary completion
- 10 Aug 2026 (actual)
- Study completion
- 10 Aug 2026 (actual)
- First posted
- 10 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is for patients with newly diagnosed glioblastoma, as well as patients who have recurring glioblastoma. Subjects will be given daily paxalisib and metformin while also maintaining a ketogenic diet.
The purpose of this study is to assess the safety of Paxalisib while maintaining a ketogenic diet (a high fat, low carbohydrate diet) and Metformin (a drug approved by the Food and Drug Administration to treat type 2 diabetes), and to see what effects it has on glioblastoma.
Detailed description
This is a two stage, two cohort phase 2 trial of a new blood-brain penetrant PI3K/mTOR inhibitor (paxalisib) combined with a ketogenic diet plus metformin in patients with either newly diagnosed MGMT unmethylated glioblastoma or patients with recurrent glioblastoma regardless of MGMT promoter methylation status.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Newly diagnosed MGMT unmethylated glioblastoma | Experimental | Drug: Paxalisib, Drug: Metformin, Other: Ketogenic Diet |
| Arm 2: Recurrent glioblastoma, regardless of methylation status | Experimental | Drug: Paxalisib, Drug: Metformin, Other: Ketogenic Diet |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Histologically-confirmed, on initial diagnosis and/or at the time of recurrence, glioblastoma (WHO Grade IV glioma); tumors situated primarily in the infratentorial compartment will be excluded.
- Radiologically-confirmed disease progression at a minimum of three months after completion of chemoradiotherapy.
- Having previously been treated with definitive fractionated radiation consistent with NCCN guidelines for radiotherapy of GBM.
- Any MGMT promoter methylation status is acceptable.
- Patients of any gender, with age ≥ 18 years at the time of randomization.
Key exclusion criteria (14 listed)
- Patients with tumors exhibiting mutated isocitrate dehydrogenase-1 or 2 (IDH-1, 2).
- Patients receiving prior treatment with bevacizumab, other PI3K inhibitors or inhibitors of the PI3K pathway (e.g. mTOR inhibitors).
- Patients currently are during the course of their illness on a ketogenic diet for more than 2 weeks.
- Patients with type 1 diabetes or poorly controlled type 2 diabetes with A1C > 7.5%.
- QT interval of ≥ 450 msec.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PaxalisibPatients will receive paxalisib starting at a dose of 45 mg/day. If well tolerated after 28 days, the dose of paxalisib will be increased to 60 mg/day. | Drug | Arm 1: Newly diagnosed MGMT unmethylated glioblastoma, Arm 2: Recurrent glioblastoma, regardless of methylation status |
| MetforminPatients will receive metformin on Cycle 1, Day 1 at a starting dose of 850 mg QD, and if tolerated, will be increased to 850 mg BID on Cycle 2, Day 1 (1700 mg/day). If that dose is tolerated, metformin will be increased to 850 mg TID (2550 mg/day) beginning on Cycle 3, Day 1. | Drug | Arm 1: Newly diagnosed MGMT unmethylated glioblastoma, Arm 2: Recurrent glioblastoma, regardless of methylation status |
| Ketogenic DietThe ketogenic diet is high-fat, low carbohydrate diet. Ketogenic diet will be maintained on a continuous basis starting on Cycle 1, Day 1 and continuing throughout the trial. | Other | Arm 1: Newly diagnosed MGMT unmethylated glioblastoma, Arm 2: Recurrent glioblastoma, regardless of methylation status |
Primary outcome
Progression-free survival, defined as the survival rate at 6 months
Time frame: At 6 months after the start of study treatment
Measured by the occurrence of a progression event as per RANO criteria or death due to any cause prior to 6 months
3 secondary outcomes
Overall survival, defined as the time of first study treatment to death from any cause
Time frame: From the start of study enrollment until death, up to approximately 18 months
Change in insulin levels
Time frame: From baseline assessments through 8 weeks post-treatment
Change in tumor glucose uptake values
Time frame: From baseline assessments through 8 weeks post-treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Howard Fine, MD principal investigator
Weill Medical College of Cornell University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Paxalisib, Metformin and Ketogenic Diet in people with Glioblastoma, run by Weill Medical College of Cornell University at 1 site 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 25 inclusion and 14 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 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Progression-free survival, defined as the survival rate at 6 months (time frame: At 6 months after the start of study treatment). 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 25 Sep 2026.