Azeliragon + Chemoradiotherapy for Glioblastoma

Recruiting in Palo Alto (17 mi)

Overseen byJiayi Huang, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Waitlist Available

Sponsor: Washington University School of Medicine

No Placebo Group

Trial Summary

What is the purpose of this trial?

Preclinical data have demonstrated the combination of azeliragon, a RAGE inhibitor, with radiation therapy (RT) can effectively reduce immune-suppressive myeloid cells and restore T-cell activation to improve tumor control in murine glioma models. Ongoing clinical studies of azeliragon with RT alone and RT plus temozolomide (TMZ) to treat patients with newly diagnosed glioblastoma (GBM) have demonstrated safety and tolerability. The purpose of this window-of-opportunity study is to validate that the combination of azeliragon with RT and TMZ would modulate immune-suppressive myeloid and T cells in the tumor microenvironment in patients with GBM.

Eligibility Criteria

This trial is for patients with a new diagnosis of glioblastoma, which is an aggressive type of brain tumor. Participants should be suitable for surgery or laser interstitial thermal therapy (LITT), and ready to undergo radiation therapy and take the drug Temozolomide. Specific inclusion and exclusion criteria details are not provided.

Inclusion Criteria

I am willing to undergo surgery to remove or treat the tumor after chemoradiotherapy.

I am 18 years old or older.

I can care for myself but may need occasional help.

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Exclusion Criteria

My cancer has spread to the lining of the brain or other areas.

Patients with concurrent participation in another interventional clinical trial or use of another investigational agent within 30 days prior to study entry

I haven't taken CYP 2C8 inhibitors in the last 2 weeks.

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Treatment Details

Interventions

Azeliragon (RAGE Inhibitor)
Radiation therapy (Radiation)

Trial OverviewThe study tests if adding Azeliragon, a drug that inhibits RAGE (a receptor involved in inflammation), to standard treatment with radiation and Temozolomide can make the immune system better at controlling tumor growth in glioblastoma patients.

Participant Groups

2Treatment groups

Experimental Treatment

Active Control

Group I: Arm 2: Neoadjuvant RT, Temozolomide (TMZ) & Azeliragon + Surgery or LITT + Adjuvant TMZ & AzeliragonExperimental Treatment4 Interventions

RT will consist of fractionated RT to 60 Gy in 30 daily fractions administered per standard of care RTOG approach. Concurrent TMZ during RT will be self-administered by mouth (PO) as per standard of care. Patients will receive azeliragon as well. Azeliragon is self-administered PO. Azeliragon dosing will consist of 6 days of a loading dose of 30 mg twice per day (days 1-6), followed by 20 mg daily starting on the 7th day. RT should ideally start on day 7, but may start up to day 21. Azeliragon should continue until the day before planned surgical procedure. 1 month after completion of RT, patient will proceed with planned surgery of either resection or LITT. Patients will then receive adjuvant TMZ and azeliragon for up to 6 months. Patient should start with the loading dose 30 mg BID for 6 days before the start of adjuvant TMZ. After 6 days, azeliragon 20 mg once daily should be continued in combination with TMZ. TMZ should ideally start on day 7, but may start up to day 21.

Group II: Arm 1: Neoadjuvant RT and Temozolomide (TMZ) + Surgery or LITT + Adjuvant TMZ & AzeliragonActive Control4 Interventions

Radiation therapy (RT) will consist of fractionated RT to 60 Gy in 30 daily fractions administered per standard of care RTOG approach. Concurrent TMZ during RT will be self-administered by mouth (PO) as per standard of care. 1 month after completion of RT, patient will proceed with planned surgery of either resection or LITT. Patients will then receive adjuvant TMZ and azeliragon for up to 6 months. Patient should start with the loading dose 30 mg BID for 6 days before the start of adjuvant TMZ. After 6 days, azeliragon 20 mg once daily should be continued in combination with TMZ. TMZ should ideally start on day 7, but may start up to day 21.