What side effects are associated with this type of intervention?

The most common treatments for Anaplastic Astrocytoma, particularly those involving CDK4/6 inhibitors like Ribociclib and mTOR inhibitors like Everolimus, have specific side effects. Ribociclib often causes neutropenia, leukopenia, fatigue, nausea, and liver enzyme abnormalities. Everolimus is associated with stomatitis, infections, rash, fatigue, diarrhea, and hyperglycemia. These side effects are important considerations in the management of Anaplastic Astrocytoma.

What prior FDA approvals exist?

The FDA has approved several treatments for Anaplastic Astrocytoma, though specific approvals for CDK4/6 inhibitors and mTOR inhibitors in this context are limited. Temozolomide, an alkylating agent, is commonly used. Bevacizumab, an anti-VEGF antibody, has also been approved for recurrent cases. While Ribociclib (a CDK4/6 inhibitor) and Everolimus (an mTOR inhibitor) are being studied for high-grade gliomas, including Anaplastic Astrocytoma, their use in this specific context has not yet received FDA approval.

What other types of research exist?

Promising novel alternatives for Anaplastic Astrocytoma patients include: 1) ONC201, an investigational oral compound targeting mitochondrial metabolism and stress response pathways, particularly for H3 K27M-mutant gliomas. 2) DNX-2401, an oncolytic adenovirus administered locally. 3) Tumor-Treating Fields (TTFields) combined with temozolomide, which has shown improved survival in glioblastoma and may be applicable to anaplastic astrocytoma. 4) Immune checkpoint inhibitors like pembrolizumab, especially in hypermutant gliomas. 5) Depatux-M (depatuxizumab mafodotin), an antibody-drug conjugate targeting EGFR-amplified gliomas.

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mTOR Inhibitor

Ribociclib + Everolimus for Brain Tumors

Phase 2

Recruiting

Led By Maryam Fouladi, MD

Research Sponsored by Nationwide Children's Hospital

Eligibility Criteria Checklist

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

Must have

Be younger than 65 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from date on treatment until date of death due to any cause or date of last follow-up, assessed up to 60 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing whether the combination of ribociclib and everolimus can help children and young adults with aggressive brain tumors live longer. Everolimus is a medication that has been approved for treating various cancers. These drugs are taken by mouth and work by stopping cancer cells from growing. The study focuses on patients whose tumors have specific genetic changes that make them hard to treat with standard therapies.

Who is the study for?

This trial is for young patients aged between 1 and 30 with high-grade gliomas, including DIPG. They must have a specific body surface area, certain genetic tumor changes, and be able to perform daily activities at least half the time. Pregnant individuals or those on certain drugs that affect liver enzymes or prolong QTc interval are excluded.

What is being tested?

The study tests Ribociclib and Everolimus in children and young adults with brain tumors like HGG/DIPG. It aims to see if these drugs can extend patients' lives by targeting specific genetic pathways involved in their cancer.

What are the potential side effects?

Possible side effects of Ribociclib and Everolimus may include risk of infections, blood count changes, fatigue, mouth sores, rash, nausea, loss of appetite, altered taste sensation, diarrhea or constipation.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from date on treatment until date of death due to any cause or date of last follow-up, assessed up to 60 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from date on treatment until date of death due to any cause or date of last follow-up, assessed up to 60 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and from date on treatment until date of death due to any cause or date of last follow-up, assessed up to 60 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Establish MTD and RP2D of ribociclib and everolimus (Part 2, Stratum D)

Number of participants with ribociclib and everolimus-related adverse events as assessed by CTCAE v5.0 (Part 1- initial feasibility study)

Overall Survival (OS) in DIPG (Part 2, Stratum B)

+1 more

Secondary study objectives

Evaluate Health-Related Quality of Life Outcomes

Number of participants with ribociclib and everolimus-related adverse events as assessed by CTCAE v5.0

Objective Response Rate (ORR) in DIPG

+2 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

4Treatment groups

Experimental Treatment

Group I: Stratum D (n=6-12)Experimental Treatment2 Interventions

Patients with metastatic/disseminated HGG, multifocal HGG, and/or gliomatosis cerebri who received craniospinal irradiation.

Group II: Stratum C (n=6-12)Experimental Treatment2 Interventions

Patients with primary thalamic, spinal cord, and/or secondary (radiation-related) HGG.

Group III: Stratum B (n=40)Experimental Treatment2 Interventions

Patients with DIPG, defined as a tumor with pontine epicenter and diffuse involvement of at least 2/3 of the pons, with histopathology consistent with diffuse WHO grade 2-4 glioma (e.g., diffuse astrocytoma, anaplastic astrocytoma, glioblastoma, H3K27-altered diffuse midline glioma).

Group IV: Stratum A (n=40)Experimental Treatment2 Interventions

Patients with localized, intracranial, non-pontine, and non-thalamic HGG (who do not meet criteria for strata B, C, or D).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ribociclib

2018

Completed Phase 3

~2420

Everolimus

2010

Completed Phase 4

~1510

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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

CDK4/6 inhibitors, such as Ribociclib, block cyclin-dependent kinases 4 and 6, preventing cell cycle progression and reducing tumor cell proliferation. mTOR inhibitors, like Everolimus, target the mTOR pathway, which is crucial for cell growth and survival, thereby reducing tumor growth and inducing apoptosis. These mechanisms are significant for Anaplastic Astrocytoma patients as they offer targeted, potentially more effective, and less toxic treatment options compared to traditional chemotherapy.

Clinical importance of eflornithine (α-difluoromethylornithine) for the treatment of malignant gliomas.