LAM561 for Pediatric Brain Tumor

Recruiting at 1 trial location

Overseen By Adrian Gerald McNicholl

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Laminar Pharmaceuticals

Must not be taking: Warfarin, Phenytoin, Sulphonylureas

Disqualifiers: Age ≥ 18, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 36

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug called LAM561 in children with severe brain and other solid tumors. The goal is to find the safest and most effective dose by adjusting it and monitoring side effects. If the drug shows benefits without severe side effects, patients can continue using it even after the trial ends.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you need warfarin, phenytoin, or certain diabetes medications. It's best to discuss your current medications with the trial team.

What makes the drug LAM561 unique for treating pediatric brain tumors?

LAM561, also known as 2-hydroxyoleic acid, is unique because it selectively targets and kills cancerous glioma cells without harming normal cells, potentially offering a safer treatment option with fewer side effects compared to traditional therapies. ^{1 2 3 4 5}

What evidence supports the effectiveness of the drug LAM561 for treating pediatric brain tumors?

Research shows that 2-hydroxyoleic acid, a component of LAM561, has anti-cancer activity and can selectively kill glioma cancer cells, a type of brain tumor, without harming normal cells. It has been tested in a clinical trial for safety and preliminary effectiveness in patients with glioma, showing potential as a treatment. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for children under 18 with advanced high-grade gliomas or other solid tumors that are getting worse, coming back, or not responding to standard treatments. They must be able to take oral medication and have good enough blood counts and organ function. Kids who can't walk due to paralysis but use a wheelchair can join too.

Inclusion Criteria

Recent mothers must agree not to breast feed while receiving medications on study.

My blood, kidney, and liver tests are within normal ranges.

My kidney function, measured by creatinine, is within the normal range for my age.

Exclusion Criteria

I have had a significant brain bleed detected by a scan in the last month.

I have high cholesterol that is hard to control or I am on medication to lower my cholesterol.

You have taken any experimental medication within a certain time frame before starting LAM561.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive LAM561 in a dose escalation phase to establish dose-limiting toxicity and a safe dose

3-18 weeks

Visits every 3 weeks for each cycle

Expanded Safety Cohort

Participants are treated at the Maximum Tolerated Dose to assess safety and determine the Recommended Phase 2 Dose

3-18 weeks

Visits every 3 weeks for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

End of study visit 30 days after last dose

Compassionate Use Extension

Participants demonstrating clinical benefit may continue treatment under compassionate use

What Are the Treatments Tested in This Trial?

Interventions

• 2-OHOA
• LAM561

Trial Overview The study tests LAM561 in two parts: first, finding the highest dose kids can handle without serious side effects (dose escalation), then giving more kids this dose to make sure it's safe (expanded safety cohort). It's an open-label trial, meaning everyone knows they're getting LAM561.

How Is the Trial Designed?

Group I: Dose Escalation Experimental Treatment 1 Intervention

The dose level corresponds to 80% of the maximum tolerated dose of LAM561 in adult patients when adjusted for body surface area. The escalation will be to the 100%, and 120% of the maximum tolerated dose of LAM561 in adult patients when adjusted for body surface area. Dose escalation decisions will be made by all active Investigators in collaboration with the Medical Monitor when at least three patients have completed the DLT observation period (Cycle 1) at each dose level. When the third patient at any given dose level has received 14 days of therapy, an "escalation teleconference" will be scheduled after that patient has completed the DLT observation period (Cycle 1). The decision to progress to the next dose level will be made on the basis of review of all significant LAM561-related toxicities.

2-OHOA is already approved in European Union, United States for the following indications:

Approved in European Union as LAM561 for:

• None approved yet; Orphan designation for glioma

Approved in United States as LAM561 for:

• None approved yet; Orphan designation for glioma and Fast-Track designation for glioblastoma

Who Is Running the Clinical Trial?

Laminar Pharmaceuticals

Lead Sponsor

Trials

4

Recruited

240+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

Laminar Pharma Inc

Collaborator

Trials

1

Recruited

30+

Hackensack Meridian Health

Collaborator

Trials

141

Recruited

42,900+

Published Research Related to This Trial

In a study of 329 glioma patients, those with high levels of SMS1 and low levels of SMS2 had a significantly better 5-year survival rate, suggesting that the expression levels of these enzymes could serve as important prognostic biomarkers.

The study found that SMS1 and SMS2 have opposing effects on glioblastoma cell growth and response to 2-Hydroxyoleic acid (2OHOA), with low basal SMS1 levels predicting a more favorable response to 2OHOA treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Opposing Contribution of SMS1 and SMS2 to Glioma Progression and Their Value in the Therapeutic Response to 2OHOA. Fernández-García, P., Rosselló, CA., Rodríguez-Lorca, R., et al.[2020]

In a Phase 1/2A trial involving 54 patients with glioma and other advanced solid tumors, the synthetic lipid 2-OHOA was found to be well-tolerated, with the most common side effects being mild nausea, vomiting, and diarrhea, establishing a recommended Phase-2 dose of 12,000 mg daily.

The treatment showed promising preliminary efficacy, particularly in patients with recurrent high-grade gliomas, where 24% experienced clinical benefits, including one patient with a remarkable response lasting over 2.5 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1/2A trial of idroxioleic acid: first-in-class sphingolipid regulator and glioma cell autophagy inducer with antitumor activity in refractory glioma. Lopez, J., Lai-Kwon, J., Molife, R., et al.[2023]

2-Hydroxyoleic acid (2OHOA) selectively induces endoplasmic reticulum (ER) stress and autophagy in human glioma cells (1321N1, SF-767, U118) without affecting normal MRC-5 cells, highlighting its potential as a targeted anti-cancer treatment.

The compound causes cell cycle arrest in glioma cells and upregulates key markers associated with ER stress and autophagy, suggesting a specific mechanism of action that contributes to its anti-cancer efficacy while minimizing toxicity to normal cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

2-Hydroxyoleic acid induces ER stress and autophagy in various human glioma cell lines. Marcilla-Etxenike, A., Martín, ML., Noguera-Salvà, MA., et al.[2021]

Octadecadienoic acid (ODA) significantly inhibits the proliferation of glioma cells and promotes their apoptosis, showing similar effects to the chemotherapy drug 5-FU in a study involving cultured human glioma cells.

The mechanisms behind ODA's effects include up-regulating apoptosis-related proteins (P21 and caspase-9) and down-regulating cell cycle proteins (P53, PI3K, and PKB/Akt), which together reduce cell division and enhance cell death.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of octadecadienoic acid on proliferation and apoptosis of glioma cells and its mechanisms]. Xie, MR., He, TX., Yuan, X., et al.[2023]

5-Lipoxygenase (5-LO) is significantly overexpressed in high-grade astrocytomas, with 90% of glioblastoma multiforme samples showing its presence, suggesting a potential role in tumor development.

Patients with tumors expressing 5-LO tend to be older and have poorer preoperative performance and shorter survival, indicating that 5-LO expression may be associated with worse clinical outcomes, although it was not directly linked to survival after adjusting for other factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased expression of 5-lipoxygenase in high-grade astrocytomas. Nathoo, N., Prayson, RA., Bondar, J., et al.[2007]

Gamma-linolenic acid (GLA) was found to be cytotoxic to malignant rat astrocytoma cells while showing no harmful effects on normal rat astrocytes, indicating its potential as a targeted treatment for cancer.

GLA not only increased the oxidative stress in astrocytoma cells but also enhanced their sensitivity to radiation therapy, suggesting that combining GLA with radiation could improve treatment outcomes for malignant astrocytoma without affecting normal cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gamma-linolenic acid (GLA) is cytotoxic to 36B10 malignant rat astrocytoma cells but not to 'normal' rat astrocytes. Vartak, S., McCaw, R., Davis, CS., et al.[2022]

Intra-cerebral injection of gamma-Linolenic acid (GLA) was found to be safe and non-toxic to normal brain cells in dogs, indicating its potential for use in human treatments.

In a study involving 15 patients with malignant gliomas, GLA administration led to tumor regression and increased patient survival by 1.5 to 2 years, suggesting its efficacy as an anti-tumor agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local application of gamma-linolenic acid in the treatment of human gliomas. Das, UN., Prasad, VV., Reddy, DR.[2022]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

The Opposing Contribution of SMS1 and SMS2 to Glioma Progression and Their Value in the Therapeutic Response to 2OHOA. [2020]

2. England pubmed.ncbi.nlm.nih.gov

A Phase 1/2A trial of idroxioleic acid: first-in-class sphingolipid regulator and glioma cell autophagy inducer with antitumor activity in refractory glioma. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

2-Hydroxyoleic acid induces ER stress and autophagy in various human glioma cell lines. [2021]

4. China pubmed.ncbi.nlm.nih.gov

[Effects of octadecadienoic acid on proliferation and apoptosis of glioma cells and its mechanisms]. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Increased expression of 5-lipoxygenase in high-grade astrocytomas. [2007]

6. England pubmed.ncbi.nlm.nih.gov

Gamma-linolenic acid (GLA) is cytotoxic to 36B10 malignant rat astrocytoma cells but not to 'normal' rat astrocytes. [2022]

7. Ireland pubmed.ncbi.nlm.nih.gov

Local application of gamma-linolenic acid in the treatment of human gliomas. [2022]