GlioblastomaPhase 1/2NCT05768919
Study of Liposomal Curcumin in Combination With RT and TMZ in Patients With Newly Diagnosed High-Grade Gliomas
A Phase 1/2 study testing Treatment Period 1, Treatment Period 2 and Treatment Period 3 in people with Glioblastoma, run by SignPath Pharma, Inc. at 2 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Treatment Period 1, Treatment Period 2 and Treatment Period 3
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesUnited States
- Study dates
- 3 Mar 2023to May 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Johns Hopkins University/Johns Hopkins Hospital
Baltimore, Maryland, 21287
Matthias Holdhoff, MD, PhD
Stuart Grossman, MD, PhD
- Recruiting
Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016
Michelle Comas, 801-557-1214, mcomas@signpathpharma.com
Solmaz Sahebjam, MD
About this study
Official title: 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
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).
Read the detailed description
This study is a Phase Ib-IIa, 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 (XRT), and TMZ and adjuvant TMZ in newly diagnosed High-Grade Gliomas.
The secondary objectives are to estimate the safety and tolerability of LC in combination with standard XRT and TMZ and adjuvant TMZ, to determine the feasibility of treatment during first 10 week.
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: up to 24 in Study Part 1 and up to 6 in Study Part 2.
All patients will be treated with open-label intravenous (IV) LC on a weekly basis for a minimum of 34 infusions which begins following healing of glioma resection and at the approximate time of the initiation of SOC XRT and TMZ therapy. Patients will have LC therapy discontinued when there is either evidence of a) disease progression, b) safety concerns leading to discontinuation, or c) the patient requests to terminate LC therapy. LC weekly treatment will be continued following 34 weeks of treatment depending on patient's desires. Regular phone (or clinic) follow-up follows cessation of LC treatment (if stopped) to capture patient data on OS and PFS.
- Conditions
- Glioblastoma
- Being tested
- Treatment Period 1, Treatment Period 2, Treatment Period 3, Treatment Period 4a
- Keywords
- High Grade Gliomas
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treatment Period 1Drug
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
Treatment Period 2Drug
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
Treatment Period 3Drug
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
Treatment Period 4aDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Treatment Period 1; Drug: Treatment Period 2; Drug: Treatment Period 3; Drug: Treatment Period 4a |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: The duration of treatment for each patient, minimum of 34 weeks
Secondary outcomes (4)
The incidence of Adverse Events
The safety and tolerability of LC in combination with standard XRT/TMZ and adjuvant TMZ will be assessed by recording the incidence of Adverse Events (AEs) using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
Subjects will undergo medical history evaluations, physical and neurological examinations, brain MRI, functional assessment using the Karnofsky Performance Scale (KPS) Index, vital sign measurements, weight, adverse event assessments, concomitant medication assessments, and laboratory testing including but not limited to blood sample collection for hematology and chemistry, urinalysis, coagulation, lipid panel, electrocardiogram, and pregnancy test for females of childbearing potential.
Measured: 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
The feasibility of weekly LC infusion will be assessed by recording the proportion of patients at each dose level who are able to complete at least 80% of the planned infusions of LC, 80% of XRT, and 60% of TMZ during the first 10 weeks of treatment.
Measured: 10 weeks
Overall Survival (OS)
The efficacy of weekly LC infusion will be assessed by recording overall survival (OS) at each dose level, defined as the duration of time from the start of treatment with LC to time of death.
Measured: 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 efficacy of weekly LC infusion will be assessed by recording progression free survival (PFS) based on Response Assessment in Neuro-Oncology (RANO) criteria at each dose level, defined as defined as the duration of time from the start of treatment with LC to time of progression or death.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2023
- Study start3 Mar 2023
- Primary completionFeb 2026 (estimated)
- Study completionMay 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- SignPath Pharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Avance Clinical Pty Ltd.
- Responsible party
- Sponsor
- Investigators
- Matthias Holdhoff, MD, Principal investigator, Johns Hopkins UniversityPeter Sordillo, MD, PhD, Study director, SignPath Pharma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05768919
- Sponsor's protocol ID
- 1004
- Status last verified
- Nov 2024
- First submitted
- 8 Feb 2023
- Last updated
- 29 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 28476779Glioblastoma cell-induced immunosuppression causing chemoresistance. Chapter in: Glioblastoma Resistance to Chemotherapy: Molecular Mechanisms and Innovative Reversal Strategies. Elsevier/Academic Press. 2021
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05768919
- Acronym / sponsor ID
- 1004
- Conditions
- Glioblastoma
- Keywords
- High Grade Gliomas
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- SignPath Pharma, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Avance Clinical Pty Ltd.
- Study start
- 3 Mar 2023 (actual)
- Primary completion
- Feb 2026 (estimated)
- Study completion
- May 2027 (estimated)
- First posted
- 15 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 Ib-IIa, 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 (XRT), and TMZ and adjuvant TMZ in newly diagnosed High-Grade Gliomas.
The secondary objectives are to estimate the safety and tolerability of LC in combination with standard XRT and TMZ and adjuvant TMZ, to determine the feasibility of treatment during first 10 week.
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: up to 24 in Study Part 1 and up to 6 in Study Part 2.
All patients will be treated with open-label intravenous (IV) LC on a weekly basis for a minimum of 34 infusions which begins following healing of glioma resection and at the approximate time of the initiation of SOC XRT and TMZ therapy. Patients will have LC therapy discontinued when there is either evidence of a) disease progression, b) safety concerns leading to discontinuation, or c) the patient requests to terminate LC therapy. LC weekly treatment will be continued following 34 weeks of treatment depending on patient's desires. Regular phone (or clinic) follow-up follows cessation of LC treatment (if stopped) to capture patient data on OS and PFS.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Tolerability, Safety, and Efficacy of LC in Combination with RT and TMZ | Experimental | Drug: Treatment Period 1, Drug: Treatment Period 2, Drug: Treatment Period 3, Drug: Treatment Period 4aDefine 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- ≥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%
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Treatment Period 1Agent: 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 | Drug | Tolerability, Safety, and Efficacy of LC in Combination with RT and TMZ |
| Treatment Period 2Agent: 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 | Drug | Tolerability, Safety, and Efficacy of LC in Combination with RT and TMZ |
| Treatment Period 3Agent: 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 | Drug | Tolerability, Safety, and Efficacy of LC in Combination with RT and TMZ |
| Treatment Period 4aAgent: 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 | Drug | Tolerability, Safety, and Efficacy of LC in Combination with RT and TMZ |
Primary outcome
The number of observed Dose Limiting Toxicity (DLTs)
Time frame: 10 weeks
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.
The number of observed Dose Limiting Toxicity (DLTs)
Time frame: The duration of treatment for each patient, minimum of 34 weeks
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.
4 secondary outcomes
The incidence of Adverse Events
Time frame: 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
Time frame: 10 weeks
Overall Survival (OS)
Time frame: 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)
Time frame: 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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2024.
- Background: PubMed 28476779Sordillo 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.
- BackgroundGlioblastoma cell-induced immunosuppression causing chemoresistance. Chapter in: Glioblastoma Resistance to Chemotherapy: Molecular Mechanisms and Innovative Reversal Strategies. Elsevier/Academic Press. 2021
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Matthias Holdhoff, MD principal investigator
Johns Hopkins University
Peter Sordillo, MD, PhD study director
SignPath Pharma
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Treatment Period 1, Treatment Period 2 and Treatment Period 3 in people with Glioblastoma, run by SignPath Pharma, Inc. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Michaella Lacoboni, RN, BSN (410-955-4009, Msheeh13@jh.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The number of observed Dose Limiting Toxicity (DLTs) (time frame: 10 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05768919, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2024.