DAY101 vs. Chemotherapy for Pediatric Brain Cancer

Recruiting in Palo Alto (17 mi)

+119 other locations

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Day One Biopharmaceuticals, Inc.

Must not be taking: Chemotherapy, Targeted therapy

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

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing tovorafenib, a medication given alone, in children with a specific type of brain tumor. The drug works by blocking a protein that helps cancer cells grow.

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.

What data supports the effectiveness of the drug DAY101 for pediatric brain cancer?

Research shows that targeted therapies like dabrafenib, which is similar to DAY101, have been effective in treating pediatric brain tumors with BRAF mutations, suggesting that DAY101 might also be effective for similar conditions. ^{1 2 3 4 5}

What makes the drug DAY101 unique for treating pediatric brain cancer?

DAY101 (also known as Tovorafenib or Ojemda) is unique because it is a targeted therapy, which means it specifically aims at certain pathways or mutations in cancer cells, potentially leading to fewer side effects compared to traditional chemotherapy that affects both healthy and cancerous cells. ^{5 6 7 8 9}

Research Team

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Chemotherapeutic Agent (Other)
• DAY101 (Other)

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.

Participant Groups

Group I: Arm #1 Experimental Treatment 1 Intervention

Tovorafenib

Group II: Arm #2 Active Control 1 Intervention

Investigator's choice of one of the following current standard of care for pediatric patients with low-grade gliomas: 1. Children's Oncology Group - Vincristine/Carboplatin (COG-V/C) 2. International Society for Paediatric Oncology - Low-Grade Glioma Vincristine/Carboplatin (SIOPe-LGG-V/C) 3. Vinblastine (VBL)

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

St. Louis Children's Hospital Saint Louis, MO

Children's of Alabama Birmingham, AL

University of Michigan - - C.S. Mott Children's Hospital Ann Arbor, MI

Arnold Palmer Hospital for Children Orlando, FL

More Trial Locations

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Singapore pubmed.ncbi.nlm.nih.gov

Drug Repurposing in Pediatric Brain Tumors: Posterior Fossa Ependymoma and Diffuse Midline Glioma under the Looking Glass. [2023]

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

Management of Inoperable Supra-Sellar Low-Grade Glioma With BRAF Mutation in Young Children. [2023]

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

Dabrafenib plus Trametinib in Pediatric Glioma with BRAF V600 Mutations. [2023]

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

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

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

Preclinical studies of 5-fluoro-2'-deoxycytidine and tetrahydrouridine in pediatric brain tumors. [2018]

6. France pubmed.ncbi.nlm.nih.gov

[Efficacy of the "8 drugs in a day" protocol in brain tumors in children]. [2015]

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

The microtubule binding drug EM011 inhibits the growth of paediatric low grade gliomas. [2013]

8. United States 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. [2021]

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

Chemotherapy of malignant brain tumors in children. [2019]