DAY101 vs. Chemotherapy for Pediatric Brain Cancer

Recruiting at 158 trial locations

Overseen By Day One Clinical Trials Information

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Day One Biopharmaceuticals, Inc.

Must not be taking: Chemotherapy, Targeted therapy

Disqualifiers: Schwannoma, NF-1, NF-2, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 60 months

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment called tovorafenib (also known as DAY101) for children and young adults with low-grade glioma, a specific type of brain tumor. Researchers aim to determine if tovorafenib is more effective and safer than standard chemotherapy treatments. Participants must have a confirmed diagnosis of this tumor type with an activating RAF alteration. This trial is for individuals who have not yet begun any systemic cancer treatment. As a Phase 3 trial, it represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those who have had prior or ongoing nonsurgical anticancer therapy for this condition.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that tovorafenib is generally well-tolerated. Research indicates that children taking tovorafenib may experience slower growth, but the treatment remains safe. The FDA has approved tovorafenib for treating certain brain tumors in children, confirming its safety for those cases. This approval provides additional confidence in its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for brain cancer?

Researchers are excited about Tovorafenib because it offers a new approach to treating pediatric brain cancer. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, Tovorafenib specifically targets a mutated protein called BRAF, which is involved in cell growth and division. This targeted mechanism may lead to fewer side effects and improved effectiveness. By honing in on the root cause of certain brain tumors, Tovorafenib has the potential to revolutionize treatment options and improve outcomes for young patients.

What evidence suggests that this trial's treatments could be effective for pediatric low-grade glioma?

Research shows that tovorafenib, a new medication, holds promise for treating a specific brain tumor in children called low-grade glioma (LGG) with certain genetic changes. In earlier studies, about 46% of children who took tovorafenib experienced tumor shrinkage within three months. The U.S. FDA has approved tovorafenib for treating some children with low-grade glioma, indicating confidence in its effectiveness. In this trial, participants will receive either tovorafenib or the investigator's choice of standard chemotherapy. These findings suggest that tovorafenib could be a promising treatment option for children with this type of brain cancer. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

This trial is for children and young adults under 25 with a type of brain tumor called low-grade glioma that has a specific genetic change (RAF alteration). They should have a measurable tumor but can't have had any previous cancer treatments like chemo or radiation, and shouldn't have certain other medical conditions or additional genetic changes in their tumors.

Inclusion Criteria

I need treatment for my condition for the first time.

My diagnosis is a type of brain tumor called glioma or glioneuronal.

At least one measurable lesion as defined by RANO criteria

Exclusion Criteria

My tumor is identified as Schwannoma, SEGA, or DIPG.

I am currently undergoing or have completed non-surgical cancer treatment.

My tumor has other gene changes that make it grow.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either tovorafenib monotherapy or standard of care chemotherapy. Treatment cycles repeat every 28 days until disease progression, unacceptable toxicity, or withdrawal.

Up to 60 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may continue therapy beyond progressive disease if deemed beneficial

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Chemotherapeutic Agent
• DAY101

Trial Overview

The study compares DAY101, which is an experimental drug, to the standard chemotherapy drugs usually given for this condition. It's designed to see which treatment works better as the first line of attack against these brain tumors in kids and young adults.

How Is the Trial Designed?

Group I: Tovorafenib Experimental Treatment 1 Intervention

Group II: Investigator's choice of Standard of care therapy Active Control 1 Intervention

Chemotherapeutic Agent is already approved in United States for the following indications:

Approved in United States as Ojemda for:

• Pediatric low-grade glioma with BRAF gene mutations

Who Is Running the Clinical Trial?

Day One Biopharmaceuticals, Inc.

Lead Sponsor

Trials

8

Recruited

1,100+

SIOPe Brain Tumor Group LOGGIC Consortium

Collaborator

Trials

1

Recruited

400+

Published Research Related to This Trial

A two-year-old girl with a low-grade glioma and a BRAF-V600E mutation showed significant improvement and near-complete tumor resolution after being treated with the targeted therapy dabrafenib, following failure of standard chemotherapy.

This case suggests that children with low-grade gliomas harboring BRAF-V600E mutations may benefit more from targeted therapies like BRAF inhibitors rather than traditional chemotherapy, highlighting the need for further clinical trials to compare these treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Inoperable Supra-Sellar Low-Grade Glioma With BRAF Mutation in Young Children. Howden, K., Chapman, S., Serletis, D., et al.[2023]

In a phase 2 trial involving 110 pediatric patients with low-grade glioma and BRAF V600 mutations, the combination of dabrafenib and trametinib resulted in a significantly higher overall response rate (47%) compared to standard chemotherapy (11%).

Dabrafenib plus trametinib also demonstrated a longer median progression-free survival (20.1 months) and a better safety profile, with fewer severe adverse events (47% vs. 94% for chemotherapy), making it a promising first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dabrafenib plus Trametinib in Pediatric Glioma with BRAF V600 Mutations. Bouffet, E., Hansford, JR., Garrè, ML., et al.[2023]

In a phase I trial involving 51 children with recurrent CNS tumors, lenalidomide was well-tolerated at doses up to 116 mg/m²/day, with myelosuppression being the primary side effect.

The trial showed some antitumor activity, with two objective responses in low-grade gliomas, indicating potential efficacy of lenalidomide in treating certain types of pediatric CNS tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of lenalidomide in pediatric patients with recurrent, refractory, or progressive primary CNS tumors: Pediatric Brain Tumor Consortium study PBTC-018. Warren, KE., Goldman, S., Pollack, IF., et al.[2021]

The study found that EM011 effectively reduces the growth of pediatric low-grade gliomas by decreasing cell proliferation and inducing apoptosis, with significant effects observed in cell viability and migration.

EM011 shows a favorable safety profile with minimal adverse side effects, making it a promising alternative to traditional treatments like radiotherapy and chemotherapy for young children with these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The microtubule binding drug EM011 inhibits the growth of paediatric low grade gliomas. Ajeawung, NF., Joshi, HC., Kamnasaran, D.[2013]

The preclinical drug development pipeline effectively identified the nucleoside analog 5-fluoro-2'-deoxycytidine (FdCyd) as having strong in vitro activity against pediatric brain tumors, significantly reducing cell proliferation at low concentrations.

Despite its promising in vitro results and adequate drug levels in the brain, FdCyd did not show a significant therapeutic response in vivo, leading to its deprioritization for clinical trials, highlighting the importance of comprehensive preclinical testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical studies of 5-fluoro-2'-deoxycytidine and tetrahydrouridine in pediatric brain tumors. Morfouace, M., Nimmervoll, B., Boulos, N., et al.[2018]

The '8 drugs in 1 day' chemotherapy regimen showed a 46% overall response rate in 54 children with various types of brain tumors, with particularly high efficacy in medulloblastomas at 76.5%.

The regimen demonstrated moderate immediate toxicity, primarily hematological, suggesting it is a safe option for use as adjuvant chemotherapy, especially in treating medulloblastomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of the "8 drugs in a day" protocol in brain tumors in children]. Chastagner, P., Olive, D., Philip, T., et al.[2015]

Pediatric CNS tumors like posterior fossa ependymoma and diffuse midline glioma share a common epigenetic vulnerability, which could be targeted with repositioned, already-approved drugs, potentially speeding up the development of new treatments.

Challenges in treating these tumors include their location, resistance to chemotherapy, and the need for drugs to effectively cross the blood-brain barrier, highlighting the importance of targeting both tumor cells and their supportive microenvironments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Repurposing in Pediatric Brain Tumors: Posterior Fossa Ependymoma and Diffuse Midline Glioma under the Looking Glass. Servidei, T., Sgambato, A., Lucchetti, D., et al.[2023]

Chemotherapy is a crucial treatment for children with brain tumors, and ongoing research is identifying factors that limit the effectiveness of these anti-cancer drugs.

Specific agents have been found to have anti-brain tumor activity, and their use in treatment requires careful consideration of dosing, delivery methods, and potential side effects, highlighting the importance of multi-institution trials to evaluate their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy of malignant brain tumors in children. Kramer, ED., Packer, RJ.[2019]

The phase II TADPOLE trial demonstrated that the combination of dabrafenib and trametinib is more effective than traditional chemotherapy for treating pediatric brain tumors with BRAF mutations, particularly in low-grade gliomas.

The trial also showed promising responses in high-grade gliomas, emphasizing the critical role of biomarker testing in tailoring treatment for pediatric glioma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Therapy Win in BRAF-Mutant Gliomas. [2023]

Citations

1.

nature.com

nature.com/articles/s41591-023-02668-y

The type II RAF inhibitor tovorafenib in relapsed/refractory ...

These data indicate that tovorafenib could be an effective therapy for BRAF-altered, relapsed/refractory pLGG.

2.

cancer.gov

cancer.gov/news-events/cancer-currents-blog/2024/pediatric-low-grade-glioma-tovorafenib-braf

Tovorafenib Approved for Some Children with Low-Grade ...

The study's investigators also noted that children's normal growth trajectory slowed during treatment with tovorafenib. Brain tumors, including ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11996598/

Tovorafenib for Relapsed or Refractory BRAF-altered ...

The major efficacy outcome measure was radiologic overall response rate (ORR), defined as the proportion of patients with complete response, partial response, ...

4.

ir.dayonebio.com

ir.dayonebio.com/news-releases/news-release-details/day-ones-ojemdatm-tovorafenib-receives-us-fda-accelerated

Day One's OJEMDA™ (tovorafenib) Receives US FDA ...

The US Food and Drug Administration (FDA) has approved OJEMDA (tovorafenib), a type II RAF inhibitor, for the treatment of patients 6 months of age and older ...

5.

ojemda.com

ojemda.com/results-with-ojemda/tumor-response-with-ojemda

Clinical study results | OJEMDA™ (tovorafenib)

ON SCREEN: 46% of children (18 out of 39) saw tumor shrinkage at 3 months after their first MRI scan* *These data were collected during the clinical study, and ...

6.

ojemda.com

ojemda.com/

OJEMDA™ (tovorafenib): Pediatric low grade-glioma (pLGG ...

OJEMDA is a prescription medicine used to treat certain types of brain tumors (cancers) called gliomas in patients 6 months and older.