Liposomal Curcumin with Radiotherapy and Temozolomide for High-Grade Gliomas

Phase I/II Study of the Tolerability, Safety, and Efficacy of Liposomal Curcumin in Combination With Radiation and Temozolomide in Patients With Newly Diagnosed High-Grade Gliomas

This study is testing if adding a new treatment called Liposomal Curcumin to standard radiotherapy and Temozolomide can be safe and effective for people newly diagnosed with high-grade gliomas.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: SignPath Pharma, Inc. (Industry-sponsored)
• Locations: 2 sites (Washington D.C., District of Columbia and 1 other locations)
• Trial ID: NCT05768919 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety, tolerability, and efficacy of Liposomal Curcumin (LC) when combined with radiotherapy (RT) and Temozolomide (TMZ) in patients newly diagnosed with high-grade gliomas. It is a Phase Ib-IIa, single-center, open-label, dose-escalation study that aims to determine the maximum tolerated dose of LC alongside standard treatments. The study will involve approximately 50 patients, with 30 expected to receive the intervention, and will monitor treatment effects over a minimum of 34 weeks. The primary focus is on assessing the safety and feasibility of this combination therapy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed high-grade gliomas planning to undergo standard therapy with RT and TMZ.

Not a fit: Patients with low Karnofsky Performance Scale scores or those not eligible for standard RT and TMZ therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could enhance treatment outcomes for patients with high-grade gliomas.

How similar studies have performed: While this approach is novel, similar studies combining adjunctive therapies with standard treatments have shown promise in improving outcomes.

Eligibility criteria

Inclusion Criteria:

1. ≥18 years of age
2. Histologically confirmed HGG (WHO grade III or IV, including GBM, astrocytoma, gliosarcoma, H3K27M mutant diffuse midline glioma). Patients with methylated or unmethylated O(6)-methylguanine-DNA methyltransferase (MGMT) promoter are eligible, as are IDH WT and mutant patients as long as the treatment plan is for combined XRT/TMZ. The neuropathologic diagnosis of HGG will be made at the respective institution. If any question arises regarding the accuracy of the neuropathologic diagnosis, slides (and pathological blocks, if necessary) will be centrally reviewed
3. Planning standard therapy with TMZ and XRT for 6 weeks and adjuvant TMZ for six 28-day cycles.
4. Karnofsky Performance Scale (KPS) ≥ 70%

   Adequate organ and marrow function defined as:
   * Hgb \> 9 g/dL
   * ANC ≥ 1500/µL
   * Platelet count ≥ 100,000/µL
   * Total bilirubin ≤ 1.5 \* institutional ULN
   * AST and ALT ≤ 3 \* institutional ULN OR
   * Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 unless data exist supporting safe use at lower values of renal function, but eGFR must be ≥ 30 mL/min/1.73 m2
5. Patients with human immunodeficiency virus (HIV) who are on effective antiretroviral therapy are eligible if the viral load was assessed as undetectable within 6 months prior to baseline
6. Women: WOCBP must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation
7. Men: must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 4 months after completion of LC administration

Exclusion Criteria:

1. Any concurrent cancer diagnosis that is untreated, actively treated, or has undergone any therapy (XRT, cytotoxic, targeted, immunotherapeutic, etc.) within 2 years of study enrollment, with the exception of squamous or basal cell skin cancer
2. Patient has not recovered from AEs due to prior anticancer therapy (i.e., residual toxicities \> Grade 1), with the exception of alopecia
3. Receiving any other investigational agent
4. Active infection requiring systemic antibiotics
5. History of allergic reaction to compounds that are chemically or biologically similar to LC
6. Patient is taking a medication that may potentiate hemolysis
7. Unstable angina or myocardial infarction within the past 6 months
8. Prolonged QTc interval, Fridericia formula (QTcF) (\> 450 msec for males or \> 460 msec for females)
9. Psychiatric illness or social situation that could limit compliance with study requirements
10. Pregnant or breastfeeding

Where this trial is running

Washington D.C., District of Columbia and 1 other locations

• Sibley Memorial Hospital — Washington D.C., District of Columbia, United States (Recruiting)
• Johns Hopkins University/Johns Hopkins Hospital — Baltimore, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Matthias Holdhoff, MD — Johns Hopkins University
• Study coordinator: Michaella Lacoboni, RN, BSN

Conditions Glioblastoma; High Grade Gliomas