What side effects are associated with this type of intervention?

Common treatments for brain tumors, such as chemotherapeutic agents like temozolomide and targeted therapies like lapatinib, have several known side effects. Temozolomide can cause myelosuppression, thrombocytopenia, and gastrointestinal issues, while lapatinib may lead to diarrhea, rash, and hepatotoxicity. Additionally, cranial radiation, often used in conjunction with these treatments, can result in neurocognitive decline, fatigue, and endocrinopathies. These side effects highlight the need for careful management and monitoring during treatment.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of brain tumors, particularly high-grade gliomas and glioblastomas. Temozolomide, an oral alkylating agent, is commonly used in combination with radiation therapy for newly diagnosed glioblastoma and as monotherapy for recurrent cases. Bevacizumab, an anti-angiogenic agent, is approved for recurrent glioblastoma, targeting the tumor's blood supply. Other investigational approaches include the use of checkpoint inhibitors like nivolumab and pembrolizumab, which aim to enhance the immune system's ability to fight the tumor. These treatments focus on disrupting tumor growth and survival pathways, similar to the investigational agent LAM561.

What other types of research exist?

Promising novel alternatives to LAM561 for brain tumor patients include: 1) LY3023414, which targets the PI3K-AKT-mTOR pathway and has shown enhanced anti-tumor activity when combined with autophagy inhibitors. 2) Ivosidenib, a mutant-IDH1 inhibitor, which has shown tolerability and efficacy in IDH1-mutant gliomas. 3) Vorasidenib, a dual mutant-IDH1/2 inhibitor, currently in phase III trials for IDH1/2-mutant gliomas. 4) Bevacizumab and everolimus, which have shown efficacy in treating refractory, progressive intracranial meningiomas.

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LAM561 for Pediatric Brain Tumor

Q: What is the mechanism of action of this treatment?

Common treatments for brain tumors include chemotherapy, targeted therapy, and antiangiogenic therapy. Chemotherapy, such as temozolomide, works by damaging the DNA of rapidly dividing tumor cells, leading to cell death. Targeted therapies, like LAM561, inhibit specific molecules involved in tumor growth and survival pathways, thereby blocking the proliferation and survival of cancer cells. Antiangiogenic therapies, such as bevacizumab, prevent the formation of new blood vessels that tumors need to grow. These treatments are crucial for brain tumor patients as they offer multiple strategies to combat tumor growth, potentially improving survival rates and quality of life.

Phase 1 & 2

Recruiting

Research Sponsored by Laminar Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

or a serum creatinine less than or equal to the institutional normal for age

Age <18 years

Must not have

A history of uncontrolled hyperlipidemia and/or the need for concurrent lipid lowering therapy

Concurrent severe and/or uncontrolled other medical disease (e.g. uncontrolled diabetes mellitus, active uncontrolled infection) that could compromise participation in the study

Timeline

Screening 3 weeks

Treatment Varies

Follow Up during cycles 1 (days 1, 8 and 15) and 2 (day 1) (each cycle is 3 weeks) and at the end of study visit (30 days of the last lam561 dose)

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects of LAM561 aren't listed here, but since there's a phase focused on finding the maximum tolerated dose without severe side effects, these could include typical chemotherapy-related issues like nausea, fatigue, lowered immunity leading to infections and potential impact on growth in children.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I am under 18 years old.

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My heart's electrical activity is normal, with no QTc prolongation.

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My liver enzyme levels are within the normal range.

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My cancer is advanced, getting worse, and standard treatments haven't worked or aren't available.

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I do not have a bleeding disorder.

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My bilirubin levels are within the normal range for my age.

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I can take pills by mouth or have a tube for medication.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I do not have any severe illnesses like uncontrolled diabetes or infections that could affect my participation.

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I don't have severe side effects from previous cancer treatments.

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I need to take warfarin, phenytoin, or certain diabetes medications.

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I have serious heart problems or had a heart attack in the last 6 months.

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I have a digestive condition that could affect how I absorb medication.

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I can take oral medications without uncontrollable vomiting.

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I am 18 years old or older.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ during cycles 1 (days 1, 8 and 15) and 2 (day 1) (each cycle is 3 weeks) and at the end of study visit (30 days of the last lam561 dose)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~during cycles 1 (days 1, 8 and 15) and 2 (day 1) (each cycle is 3 weeks) and at the end of study visit (30 days of the last lam561 dose)

This trial's timeline: 3 weeks for screening, Varies for treatment, and during cycles 1 (days 1, 8 and 15) and 2 (day 1) (each cycle is 3 weeks) and at the end of study visit (30 days of the last lam561 dose) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Safety and Tolerability of LAM561

To identify the Recommended Phase 2 Dose (RP2D) of LAM561 in pediatric patients

Secondary study objectives

Characterize LAM561 PK profile

To assess the preliminary anti-tumor efficacy of LAM561

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Dose EscalationExperimental Treatment1 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

LAM561

2018

Completed Phase 2

~80

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for brain tumors include chemotherapy, targeted therapy, and antiangiogenic therapy. Chemotherapy, such as temozolomide, works by damaging the DNA of rapidly dividing tumor cells, leading to cell death. Targeted therapies, like LAM561, inhibit specific molecules involved in tumor growth and survival pathways, thereby blocking the proliferation and survival of cancer cells. Antiangiogenic therapies, such as bevacizumab, prevent the formation of new blood vessels that tumors need to grow. These treatments are crucial for brain tumor patients as they offer multiple strategies to combat tumor growth, potentially improving survival rates and quality of life.

Bioinformatics analysis reveals potential candidate drugs for different subtypes of glioma.