PI3K-beta Inhibitor for Tumors

No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, GSK2636771 (a PI3K-beta inhibitor), designed to shrink or halt the growth of tumors with a specific genetic change called a PTEN mutation. The treatment blocks a protein called PI3K-beta, which may play a role in cancer cell growth. Eligible participants are those with cancer exhibiting PTEN mutations, confirmed by a test called immunohistochemistry. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken certain cancer treatments targeting the PI3K beta, AKT, or mTOR pathways before. If you are on anti-platelet drugs like clopidogrel, you cannot participate.

Is there any evidence suggesting that GSK2636771 is likely to be safe for humans?

Research has shown that GSK2636771, a drug targeting a specific protein, has undergone safety testing in people. Diarrhea, nausea, and vomiting were the most common side effects reported in earlier studies where patients took GSK2636771, sometimes with other treatments.

The drug is now in phase 2 trials, indicating it has already been tested for safety in humans. Although the FDA has not yet approved it, current information suggests the drug is generally well-tolerated. However, as with any new drug under study, there is always a risk of side effects. Participants should discuss these risks with their doctor.12345

Why do researchers think this study treatment might be promising?

Researchers are excited about GSK2636771 because it targets the PI3K-beta pathway, which is often linked to tumor growth in certain cancers. Unlike standard treatments that may not specifically target this pathway, GSK2636771 aims to block the signals that allow cancer cells to multiply. This precise mechanism could lead to more effective management of the disease with potentially fewer side effects, offering hope for better outcomes in patients with tumors driven by this pathway.

What evidence suggests that GSK2636771 might be an effective treatment for tumors with PTEN mutations?

Research has shown that GSK2636771 targets a protein called PI3K-beta, which may aid cancer cell growth, particularly in tumors with PTEN mutations. In earlier studies, some patients with these mutations experienced disease stabilization, with about 32% achieving this stable state. Additionally, another study found that a small number of patients saw their tumors shrink by more than half, known as a partial response. These findings suggest that GSK2636771 might slow down or reduce cancer growth in certain patients.34567

Who Is on the Research Team?

FJ

Filip Janku

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for cancer patients with a specific genetic change called PTEN mutation or deletion. They must have some PTEN expression, normal hemoglobin levels, acceptable kidney function, and a stable heart rhythm on an ECG. Excluded are those allergic to GSK2636771, with certain other gene changes that affect cancer growth pathways, prior treatments targeting similar pathways, history of lung disease like pneumonitis, congenital platelet defects or current use of certain anti-platelet drugs.

Inclusion Criteria

My cancer does not show a complete loss of PTEN by IHC.
My cancer shows PTEN protein presence.
My kidney function, measured by creatinine levels or clearance, is within the required range.
See 4 more

Exclusion Criteria

I have not been treated with drugs targeting PI3K beta, AKT, or mTOR.
I have never had interstitial lung disease or pneumonitis.
I am not allergic to GSK2636771 or similar drugs.
See 3 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PI3K-beta inhibitor GSK2636771 orally once daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 3 years
Tumor assessments at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 3 months if less than 2 years from study entry, and then every 6 months for year 3.

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

  • GSK2636771
Trial Overview The trial tests the drug GSK2636771 in cancers with PTEN mutations. This drug aims to block PI3K-beta protein which might be essential for the growth of these cancer cells. The goal is to see if this targeted treatment can shrink tumors or halt their progression.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Treatment (GSK2636771)Experimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Published Research Related to This Trial

In a phase I study involving 170 patients with advanced solid tumors, GSK2126458 (GSK458) was found to have a maximum tolerated dose (MTD) of 2.5 mg once daily, with common side effects including diarrhea and skin rash.
The study showed that GSK458 led to durable objective responses in various cancer types, and interestingly, these responses were not dependent on PIK3CA mutations, suggesting that other factors may influence treatment efficacy.
First-in-Human Phase I Study of GSK2126458, an Oral Pan-Class I Phosphatidylinositol-3-Kinase Inhibitor, in Patients with Advanced Solid Tumor Malignancies.Munster, P., Aggarwal, R., Hong, D., et al.[2021]
GSK2636771, a selective inhibitor of the PI3Kβ pathway, was found to have a manageable safety profile with dose-limiting toxicities including hypophosphatemia and hypocalcemia, and the recommended phase II dose was established at 400 mg once daily.
In a study of 65 patients with advanced solid tumors, particularly those with PIK3CB alterations, GSK2636771 showed promising antitumor activity, with some patients experiencing durable clinical benefits lasting over 24 weeks.
A First-Time-in-Human Study of GSK2636771, a Phosphoinositide 3 Kinase Beta-Selective Inhibitor, in Patients with Advanced Solid Tumors.Mateo, J., Ganji, G., Lemech, C., et al.[2022]

Citations

1.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/40865033/
PIK3CB Inhibitor GSK2636771 in Cancers With PTEN ...Among 24 patients whose tumors had PTEN mutation/deletion but retained PTEN expression (arm N), seven patients (32%) achieved stable disease (SD) ...
A First-Time-in-Human Study of GSK2636771, a ...We present preclinical studies conducted to characterize the effect and define the optimal target population for development of GSK2636771, a selective p110β ...
Phase I/II study of the selective PI3Kβ inhibitor ...Among 11 evaluable pts at 200mg daily of GSK2636771, partial response (PR) was achieved in 2 pts (-56% and -59% as compared to baseline, per ...
NCT03131908 | Study of the Selective PI3K-Beta Inhibitor ...The goal of this clinical research study is to learn if GSK2636771 given in combination with pembrolizumab can help to control the disease in patients with ...
Development and safety of PI3K inhibitors in cancer - PMCEven so, no further clinical trials have shown its effectiveness. Although GSK2636771 plus enzalutamide was tolerated in patients with ...
Safety results from phase I/II study of the PI3Kβ inhibitor ...Safety results from phase I/II study of the PI3Kβ inhibitor GSK2636771 (G) in combination with pembrolizumab (P) in patients (pts) with PD-1 ...
Safety results from phase I/II study of the PI3Kβ inhibitor ...Safety results from phase I/II study of the PI3Kβ inhibitor GSK2636771 (G) in combination with pembrolizumab (P) in patients (pts) with PD-1 refractory ...
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