Trial Title:
Study of Liposomal Curcumin in Combination With RT and TMZ in Patients With Newly Diagnosed High-Grade Gliomas
NCT ID:
NCT05768919
Condition:
Glioblastoma
Conditions: Official terms:
Glioblastoma
Glioma
Conditions: Keywords:
High Grade Gliomas
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Intervention model description:
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. 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.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Concurrent CRT Period
Description:
Agent: LipoCurc Premedication/Precautions: Dexamethasone 4mg IV, Diphenhydramine 25 mg IV
- Dose: per treatment assignment Route: IV over 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
Arm group label:
Tolerability, Safety, and Efficacy of LC in Combination with RT and TMZ
Intervention type:
Drug
Intervention name:
Post-CRT Period
Description:
Agent: LipoCurc Premedication/Precautions: Dexamethasone 4 mg IV Diphenhydramine 25 mg IV
Dose: Per treatment assignment Route: IV over 3 hours Schedule: Weekly: Weeks 7,8,9,10
Cycle length: 4 weeks
Arm group label:
Tolerability, Safety, and Efficacy of LC in Combination with RT and TMZ
Intervention type:
Drug
Intervention name:
Adjuvant Period
Description:
Agent: LipoCurc Premedication/Precautions: Dexamethasone 4 mg IV Diphenhydramine 25 mg IV
Dose: Per treatment assignment Route: IV over 3 hours Schedule: Weekly: Adjuvant Cycles
1-6: 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
Arm group label:
Tolerability, Safety, and Efficacy of LC in Combination with RT and TMZ
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).
Detailed description:
This study is a Phase 1/2, single-center, single-institution, open-label, dose-escalation
study in patients with newly diagnosed high-grade malignant gliomas. Dose finding will be
performed using a time-to-event Bayesian optimal interval (TITE-BOIN) rule-based schema.
The primary objectives of the study are to determine the maximum tolerated dose
/recommended phase 2 dose of Liposomal Curcumin (LC) in combination with radiotherapy
(RT), and TMZ and adjuvant TMZ in newly diagnosed High-Grade Gliomas, and to determine
the safety and tolerability of LC IV infused over 3-hours.
The secondary objectives are to estimate the safety and tolerability of LC in combination
with standard RT and TMZ and adjuvant TMZ, to determine the feasibility of weekly LC
infusion, defined as the number of patients being able to complete 80% of the planned
doses of LC, 80% of RT, and 60% of TMZ within the first 10 weeks of treatment, and to
assess efficacy as defined by overall survival (OS) and progression free survival (PFS)
observed for each dose level.
This study is an unblinded, sequential treatment intervention employing 3 dose levels.
Approximately 50 patients will be screened to achieve up to 30 patients assigned to study
intervention.
The duration of treatment for each patient will be up to 34 weeks. Treatment starts with
the beginning of infusion and ends, if tolerated, at the end of Cycle 6 of adjuvant TMZ.
Criteria for 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
RT/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 RT for 6 weeks
4. Karnofsky Performance Scale (KPS) ≥ 60%
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
- Creatinine ≤ 1.5 * 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 (RT, 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 (ie, 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 (see Protocol Section 5.5.1.2 and Section 5.5.1.3 of protocol)
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, Bazett formula (QTcB) (> 450 msec for males or > 460 msec
for females)
9. Psychiatric illness or social situation that could limit compliance with study r
requirements
10. Pregnant or breastfeeding
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Johns Hopkins University/Johns Hopkins Hospital
Address:
City:
Baltimore
Zip:
21287
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Matthias Holdhoff, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Stuart Grossman, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
David Kamson, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Jaishri Blakeley, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Lawrence Kleinberg, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
John Laterra, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Kristin Redmond, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Karisa Schreck, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Carlos Romo, MD, PhD
Email:
Sub-Investigator
Start date:
March 3, 2023
Completion date:
May 2027
Lead sponsor:
Agency:
SignPath Pharma, Inc.
Agency class:
Industry
Collaborator:
Agency:
Avance Clinical Pty Ltd.
Agency class:
Industry
Source:
SignPath Pharma, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05768919
