41 Participants Needed

Savolitinib for Brain Tumors

Recruiting at 11 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 1 JurisdictionThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of volitinib in treating patients with primary central nervous system (CNS) tumors that have come back (recurrent) or does not respond to treatment (refractory). Volitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain medications that affect the liver enzyme CYP3A4 or herbal supplements like St. John's wort. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Savolitinib for brain tumors?

The research highlights the potential of targeted therapies like receptor tyrosine kinase inhibitors, which are similar to Savolitinib, in treating brain tumors by regulating growth factor signaling pathways. This suggests that Savolitinib, which targets similar pathways, might be effective for brain tumors.12345

How is the drug Savolitinib unique for treating brain tumors?

Savolitinib is unique because it specifically targets the MET receptor tyrosine kinase, which is often involved in the growth and spread of certain types of tumors, including brain tumors. This targeted approach may offer a new option for patients with brain tumors, especially when other treatments have not been effective.46789

Research Team

RS

Ralph Salloum

Principal Investigator

Pediatric Brain Tumor Consortium

Eligibility Criteria

This trial is for young patients aged 5 to 21 with recurrent or stubborn primary CNS tumors, including medulloblastoma and gliomas. They must have tried standard treatments without success, be able to swallow tablets, and have stable neurological conditions. Pregnant women, nursing mothers, those with serious infections or other significant illnesses are excluded.

Inclusion Criteria

I can swallow whole tablets.
My blood, liver, kidney, and heart are functioning within normal ranges.
I recently completed a specific type of radiation therapy.
See 21 more

Exclusion Criteria

I do not have any major illnesses or organ problems unrelated to my cancer.
I am currently on other treatments.
Patients with a history of allergic reactions attributed to compounds of similar composition
See 6 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive volitinib orally once daily. Treatment repeats every 28 days for up to 39 courses in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, X-ray imaging, and MRI scans throughout study.

Up to 1092 days (39 courses of 28 days each)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days, then periodically for up to 2 years.

Up to 2 years

Treatment Details

Interventions

  • Savolitinib
Trial OverviewThe trial tests the safety and optimal dosage of volitinib on children and young adults with specific brain tumors that haven't responded to previous treatments. It involves biospecimen collection and imaging techniques like MRI alongside the administration of volitinib.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (volitinib)Experimental Treatment4 Interventions
Patients receive volitinib PO QD. Treatment repeats every 28 days for up to 39 courses in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, X-ray imaging, and MRI scans throughout study.

Savolitinib is already approved in China for the following indications:

🇨🇳
Approved in China as Orpathys for:
  • Non-small cell lung cancer (NSCLC) with MET exon 14 skipping alterations

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Findings from Research

In the phase 2 FIREFLY-1 trial, tovorafenib demonstrated a high overall response rate of 67% in treating pediatric low-grade glioma (pLGG) with BRAF alterations, with a median duration of response of 16.6 months.
While tovorafenib shows promise as an effective therapy, it is associated with notable treatment-related adverse events, including hair color changes (76%) and elevated creatine phosphokinase (56%), with 42% of patients experiencing grade ≥3 adverse events.
The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial.Kilburn, LB., Khuong-Quang, DA., Hansford, JR., et al.[2023]
In a study of 10 patients with recurrent malignant glioma, the combination of apatinib and irinotecan resulted in a 55% objective response rate and a 78% disease control rate, indicating promising efficacy for this treatment approach.
The treatment was generally well-tolerated, with the most common side effects being gastrointestinal reactions, hypertension, and myelosuppression, suggesting that while there are some risks, the safety profile is manageable.
A pilot clinical study of apatinib plus irinotecan in patients with recurrent high-grade glioma: Clinical Trial/Experimental Study.Wang, L., Liang, L., Yang, T., et al.[2022]
Targeted therapies, such as receptor tyrosine kinase inhibitors and farnesyl transferase inhibitors, are being investigated to address the abnormal growth factor signaling pathways that contribute to brain tumor development, which are often resistant to traditional treatments.
Clinical trials are currently testing several of these targeted agents, including imatinib mesylate and gefitinib, in patients with high-grade gliomas, aiming to improve survival and quality of life for those affected by these aggressive tumors.
Molecular neuro-oncology and development of targeted therapeutic strategies for brain tumors. Part 1: Growth factor and Ras signaling pathways.Newton, HB.[2007]

References

The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial. [2023]
A pilot clinical study of apatinib plus irinotecan in patients with recurrent high-grade glioma: Clinical Trial/Experimental Study. [2022]
Molecular neuro-oncology and development of targeted therapeutic strategies for brain tumors. Part 1: Growth factor and Ras signaling pathways. [2007]
Synergistic activity of mTORC1/2 kinase and MEK inhibitors suppresses pediatric low-grade glioma tumorigenicity and vascularity. [2021]
Phase II trial of dacomitinib, a pan-human EGFR tyrosine kinase inhibitor, in recurrent glioblastoma patients with EGFR amplification. [2022]
Sorafenib/regorafenib and lapatinib interact to kill CNS tumor cells. [2021]
Phase I trial of dovitinib (TKI258) in recurrent glioblastoma. [2018]
Dabrafenib Treatment in a Patient with an Epithelioid Glioblastoma and BRAF V600E Mutation. [2022]
Growth-factor-driven rescue to receptor tyrosine kinase (RTK) inhibitors through Akt and Erk phosphorylation in pediatric low grade astrocytoma and ependymoma. [2018]