Study of Liposomal Curcumin in Combination With RT and TMZ in Patients With Newly Diagnosed High-Grade Gliomas

NCT05768919 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 1004
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

The objective of this study is to assess the tolerability, safety, and efficacy of Liposomal Curcumin (LC) in combination with radiotherapy (RT) and Temozolomide (TMZ) in patients with newly diagnosed High-Grade Gliomas (HGG).

Conditions

Glioblastoma

Keywords

High Grade Gliomas

Outcome Measures

Primary Outcomes (2)

• The number of observed Dose Limiting Toxicity (DLTs)

  The MTD/RP2D of LC in combination with XRT and TMZ and adjuvant TMZ in newly diagnosed HGG will be determined by recording the number of observed dose limiting toxicities (DLTs). DLTs, as defined in this study occur if in the first three patients entered at a dose-level, more than one of these 3 experiences a serious adverse event, as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5. If one of the first three patients entered at the level experiences an SAE (as defined by NCI CTCAE Version 5), then three additional patients are entered at that same dose level. If one of the additional three patients experiences an SAE (as defined by NCI CTCAE Version 5), the dose is not advanced beyond that level.

  10 weeks

• The number of observed Dose Limiting Toxicity (DLTs)

  The safety and tolerability of LC infused IV over 3 hours will be assessed by recording the number of observed DLTs. DLTs, as defined in this study occur if in the first three patients entered at a dose-level, more than one of these 3 experiences a serious adverse event, as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5. If one of the first three patients entered at the level experiences an SAE (as defined by NCI CTCAE Version 5), then three additional patients are entered at that same dose level. If one of the additional three patients experiences an SAE (as defined by NCI CTCAE Version 5), the dose is not advanced beyond that level.

  The duration of treatment for each patient, minimum of 34 weeks

Secondary Outcomes (4)

• The incidence of Adverse Events

  The duration of treatment for each patient, minimum of 34 weeks

• The proportion of patients at each dose level who receive at least 80% of the planned infusions of LC, 80% of XRT, and 60% of TMZ during the first 10 weeks of treatment

  10 weeks

• Overall Survival (OS)

  The duration of treatment for each patient, minimum of 34 weeks; OS is time from beginning of therapy to time of death.

• Progression free survival (PFS)

  The duration of treatment for each patient, minimum of 34 weeks; PFS is time from the start of therapy until the date when tumor progression is documented

Study Arms (1)

Tolerability, Safety, and Efficacy of LC in Combination with RT and TMZ

EXPERIMENTAL

Define the MTD/recommended Phase 2 dose (RP2D) of LC, administered IV weekly in combination with standard CRT (60 Gy in 30-33 fractions M-F, and daily oral TMZ 75 mg/m2), in patients with high grade malignant gliomas. This study seeks the MTD/RP2D of LC when added to TMZ during concurrent RT and adjuvant TMZ after RT. The study will evaluate escalating doses of LC delivered by IV infusion weekly as a gravity infusion (without infusion pump). Within each cohort, the dose will remain the same. In the first cohort, dosing will begin at Level 1 (300 mg/m2). The infusion of LC will begin at the start of CRT. Patients will be evaluable for the cohort if they have completed 80% of the planned doses of LC, 80% of RT and 60% of TMZ within the first 10 weeks of treatment. Patients who experience a dose-limiting toxicity (DLT) will be evaluable for the cohort if they have received at least 1 dose of LC.

Drug: Treatment Period 1; Drug: Treatment Period 2; Drug: Treatment Period 3; Drug: Treatment Period 4a

Interventions

Treatment Period 1 DRUG

Agent: LipoCurc Premedication/Precautions: Dexamethasone 4mg IV, Diphenhydramine 25 mg IV - Dose: per treatment assignment Route: IV over approximately 3 hours Schedule: Weekly: Weeks 1,2, 3,4,5,6 Cycle length: 6 weeks Agent: TMZ Premedications/Precautions No food 2 hr before and after dosing Antiemetic (eg, ondansetron, prochlorperazine) 30 minutes before dosing Stool softener PRN. Dose: 75 mg/m2 Route: Oral Schedule: Daily during term of RT Cycle Length: 6 weeks Agent: Radiotherapy Premedications/Precautions: n/a Dose: 2 Gy Route: External beam therapy Schedule: Monday-Friday Cycle Length 6 weeks

Tolerability, Safety, and Efficacy of LC in Combination with RT and TMZ

Treatment Period 2 DRUG

Agent: LipoCurc Premedication/Precautions: Dexamethasone 4 mg IV Diphenhydramine 25 mg IV Dose: Per treatment assignment Route: IV over approximately 3 hours Schedule: Weekly: Weeks 7,8,9,10 Cycle length: 4 weeks

Tolerability, Safety, and Efficacy of LC in Combination with RT and TMZ

Treatment Period 3 DRUG

Agent: LipoCurc Premedication/Precautions: Dexamethasone 4 mg IV Diphenhydramine 25 mg IV Dose: Per treatment assignment Route: IV over approximately 3 hours Schedule: Weekly: Adjuvant Cycles 11-34 Weeks 1, 2, 3, 4 of each cycle Cycle Length: 4 weeks Agent: TMZ Premedication/Precautions: No food 2 hr before and after dosing. Antiemetic (eg, ondansetron, prochlorperazine) 30 minutes before dosing Stool softener prn Dose: 150-200 mg/m2 (Cycles 1-6) Route: Oral Schedule: Daily Cycle Length: 4 weeks

Tolerability, Safety, and Efficacy of LC in Combination with RT and TMZ

Treatment Period 4a DRUG

Agent: LipoCurc Premedication/Precautions: Dexamethasone 4 mg IV Diphenhydramine 25 mg IV Dose: Per treatment assignment Route: IV over approximately 3 hours Schedule: Weekly: 35+ Weeks 1, 2, 3, 4 of each cycle Cycle Length: 4 weeks

Tolerability, Safety, and Efficacy of LC in Combination with RT and TMZ

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years of age
• 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
• Planning standard therapy with TMZ and XRT for 6 weeks and adjuvant TMZ for six 28-day cycles.
• 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
• 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
• 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
• 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

You may not qualify if:

• 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
• Patient has not recovered from AEs due to prior anticancer therapy (i.e., residual toxicities \> Grade 1), with the exception of alopecia
• Receiving any other investigational agent
• Active infection requiring systemic antibiotics
• History of allergic reaction to compounds that are chemically or biologically similar to LC
• Patient is taking a medication that may potentiate hemolysis
• Unstable angina or myocardial infarction within the past 6 months
• Prolonged QTc interval, Fridericia formula (QTcF) (\> 450 msec for males or \> 460 msec for females)
• Psychiatric illness or social situation that could limit compliance with study requirements
• Pregnant or breastfeeding

Sponsors & Collaborators

• SignPath Pharma, Inc.: lead
• Avance Clinical Pty Ltd.: collaborator

Study Sites (2)

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

RECRUITING

Johns Hopkins University/Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

RECRUITING

Related Publications (2)

• Sordillo PP, Sordillo LA, Helson L. The Kynurenine Pathway: A Primary Resistance Mechanism in Patients with Glioblastoma. Anticancer Res. 2017 May;37(5):2159-2171. doi: 10.21873/anticanres.11551.

  PMID: 28476779 BACKGROUND

• Glioblastoma cell-induced immunosuppression causing chemoresistance. Chapter in: Glioblastoma Resistance to Chemotherapy: Molecular Mechanisms and Innovative Reversal Strategies. Elsevier/Academic Press. 2021

  BACKGROUND

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Matthias Holdhoff, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Peter Sordillo, MD, PhD

  SignPath Pharma

  STUDY DIRECTOR

Central Study Contacts

Michaella Lacoboni, RN, BSN

CONTACT

410-955-4009; Msheeh13@jh.edu

Michelle Comas

CONTACT

801-557-1214; mcomas@signpathpharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study seeks the MTD/RP2D of LC when added to TMZ during concurrent XRT and adjuvant TMZ after XRT. The study will evaluate escalating doses of LC delivered by IV infusion weekly as a gravity infusion (without infusion pump). Within each cohort, the dose will remain the same. In the first cohort, dosing will begin at Level 1 (300 mg/m2). The infusion of LC will begin at the start of CRT. Patients will be evaluable for the cohort if they have completed 80% of the planned doses of LC, 80% of RT and 60% of TMZ within the first 10 weeks of treatment. Patients who experience a dose-limiting toxicity (DLT) will be evaluable for the cohort if they have received at least 1 dose of LC. There will be a maximum of 4 dose levels assessed in this study. The Safety Review Committee (SRC) will oversee dose level decisions throughout the dose escalation phase of the study.

Study Record Dates

• First Submitted: February 8, 2023
• First Posted: March 15, 2023
• Study Start: March 3, 2023
• Primary Completion: February 1, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: November 29, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)