Erdafitinib for Brain Cancer

Recruiting at 27 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP2C9 inducers, CYP3A4 inducers

Disqualifiers: Pregnancy, Uncontrolled illness, FGFR inhibitors, others

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

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Up to 2 years

35 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but you cannot take medications that are moderate CYP2C9 inducers or strong CYP3A4 inducers. It's important to discuss your current medications with the trial team to ensure there are no interactions with erdafitinib.

What data supports the effectiveness of the drug Erdafitinib (Balversa) for brain cancer?

Erdafitinib is approved for treating certain types of bladder cancer and is being studied for other cancers, but there is no direct evidence of its effectiveness for brain cancer. However, similar drugs like gefitinib have shown some benefits in treating brain metastases in lung cancer patients, suggesting potential for further research. ^{1 2 3 4 5}

Is erdafitinib safe for humans?

Erdafitinib, also known as Balversa, has been approved for treating certain types of bladder cancer and is being studied for other cancers. Some safety concerns include the potential for eye problems, as a case of secondary maculopathy (eye disease) was reported in a patient using erdafitinib. ^{1 2 6 7 8}

What makes the drug erdafitinib unique for treating brain cancer?

Erdafitinib is unique because it is a pan-fibroblast growth factor receptor (FGFR) inhibitor, which is different from other treatments like erlotinib and gefitinib that target the epidermal growth factor receptor (EGFR). This distinct mechanism of action may offer a new approach for treating brain cancer, especially if FGFR is involved in the cancer's growth. ^{1 2 4 9 10}

What is the purpose of this trial?

This phase II trial tests how well erdafitinib works in controlling IDH-wild type (WT), FGFR-TACC gene fusion positive gliomas that have come back after a period of improvement (recurrent) or that are growing, spreading, or getting worse (progressive). Erdafitinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal FGFR protein that signals tumor cells to multiply. This may help keep tumor cells from growing and may kill them. Giving erdafitinib may help to slow the growth of, or to shrink, tumor cells in patients with recurrent or progressive IDH-wild type gliomas with FGFR-TACC gene fusion.

Research Team

Macarena I De La Fuente

Principal Investigator

University Health Network Princess Margaret Cancer Center LAO

Eligibility Criteria

Adults with specific brain cancers called IDH-wild type gliomas that have returned or worsened, despite previous treatments. Participants must be over 18 and have tumors with a particular gene fusion (FGFR-TACC). The cancer should show growth on scans and not be due to other conditions like radiation effects or infections.

Inclusion Criteria

I can understand and am willing to sign the consent form myself or have someone legally authorized to do so on my behalf.

I am HIV positive, on treatment, and my viral load is undetectable.

My high-grade brain tumor has worsened 12 weeks after finishing treatment.

Exclusion Criteria

Pregnant women are excluded from this study

Patients with uncontrolled intercurrent illness

History of allergic reactions attributed to compounds of similar chemical or biologic composition to erdafitinib

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive erdafitinib orally once daily on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 2 years

Monthly visits for MRI, OCT, and blood sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

2 years

Every 3 months

Treatment Details

Interventions

• Erdafitinib

Trial Overview The trial is testing Erdafitinib, a drug designed to block abnormal proteins in tumor cells which may slow down or shrink the growth of recurrent or progressive brain tumors. It includes imaging tests like MRI and collecting tissue samples to study the drug's effect.

Participant Groups

Group I: Treatment (erdafitinib) Experimental Treatment 4 Interventions

Patients receive erdafitinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI, OCT, and collection of blood samples throughout the trial.

Erdafitinib is already approved in United States, European Union for the following indications:

Approved in United States as Balversa for:

• Locally advanced or metastatic urothelial carcinoma with susceptible FGFR3 genetic alterations

Approved in European Union as Balversa for:

• Locally advanced or metastatic urothelial carcinoma with susceptible FGFR3 genetic alterations

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Erdafitinib, a tyrosine kinase inhibitor for advanced urothelial carcinoma, was studied using a pharmacokinetic model in mice and rats to determine effective dosing for phase 1 trials, showing that doses above 4 mg/day resulted in significant tumor growth inhibition.

The modeling predicted that efficacious unbound concentrations of erdafitinib were identified, aligning with early clinical activity observed at a dose of 6 mg in the first-in-human trial, demonstrating the potential of translational modeling in optimizing drug dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A translational model-based approach to inform the choice of the dose in phase 1 oncology trials: the case study of erdafitinib. Tosca, EM., Terranova, N., Stuyckens, K., et al.[2022]

Erdafitinib is a newly approved pan-FGFR inhibitor specifically for treating locally advanced or metastatic urothelial carcinoma associated with FGFR3 or FGFR2 mutations.

The drug is also being explored for its potential effectiveness against various other cancers, including cholangiocarcinoma and non-small cell lung cancer, indicating its broad therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erdafitinib: First Global Approval. Markham, A.[2020]

In a study of 393 patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC), lazertinib significantly improved median intracranial progression-free survival to 28.2 months compared to 8.4 months for gefitinib, indicating its superior efficacy in patients with central nervous system (CNS) metastases.

Lazertinib also showed a higher intracranial objective response rate (94% vs. 73% for gefitinib) among patients with measurable CNS lesions, suggesting it may provide more durable responses, while tolerability was similar to that observed in the overall study population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Central Nervous System Outcomes of Lazertinib Versus Gefitinib in EGFR-Mutated Advanced NSCLC: A LASER301 Subset Analysis. Soo, RA., Cho, BC., Kim, JH., et al.[2023]

In a phase II trial involving 57 patients with recurrent glioblastoma, gefitinib was found to be well tolerated, with mild adverse effects primarily consisting of skin reactions and diarrhea, and only 6% of patients withdrawing due to drug-related side effects.

Despite no objective tumor responses observed, gefitinib showed some activity with a 6-month event-free survival rate of 13% and a median overall survival of 39.4 weeks, suggesting potential benefits that warrant further investigation at higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of gefitinib in recurrent glioblastoma. Rich, JN., Reardon, DA., Peery, T., et al.[2022]

Gefitinib, a medication used for non-small-cell lung cancer (NSCLC), has shown clinical activity in some patients with brain metastases, leading to improvements in neurological and systemic symptoms.

Case studies indicate that gefitinib can result in partial and even complete responses in brain metastases, suggesting the need for larger trials to better understand its efficacy and potential role in treatment, especially in combination with radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality-of-life benefits and evidence of antitumour activity for patients with brain metastases treated with gefitinib. Katz, A., Zalewski, P.[2018]

A 58-year-old man developed blurry vision and secondary maculopathy after 3 weeks of treatment with erdafitinib for bladder cancer, indicating potential ocular toxicity associated with this medication.

Discontinuation of erdafitinib led to improvements in both vision and eye health, highlighting the need for monitoring ocular side effects in patients receiving FGFR inhibitors like erdafitinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erdafitinib-Induced Secondary Maculopathy. Becker, B., El Hamichi, S., Gold, AS., et al.[2023]

Erlotinib shows promise for treating brain metastases in non-small cell lung cancer (NSCLC) patients, particularly those with EGFR mutations, as it can penetrate the central nervous system and has demonstrated objective responses in preclinical and retrospective studies.

However, in non-EGFR mutation enriched populations, adding erlotinib to radiotherapy did not improve progression-free or overall survival, indicating that its use remains investigational and may be most beneficial for specific patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erlotinib for the treatment of brain metastases in non-small cell lung cancer. Brower, JV., Robins, HI.[2018]

Erlotinib, a drug used to treat primary brain tumors in children, was well tolerated among 47 patients aged 0.7 to 19 years, with most reported side effects being mild (grade 1).

The study found that younger patients (under 5 years) and males had higher drug clearance rates, but no adjustments to dosing based on age or genetic factors are recommended, indicating consistent efficacy and safety across the pediatric population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety of erlotinib and its metabolite OSI-420 in infants and children with primary brain tumors. Reddick, SJ., Campagne, O., Huang, J., et al.[2023]

Erlotinib, a drug that targets the epidermal growth factor receptor (EGFR), was well tolerated in a study involving four adult rhesus monkeys, showing a mean terminal half-life of 5.2 hours after intravenous administration.

Both erlotinib and its active metabolite OSI-420 were detectable in cerebrospinal fluid (CSF), but their penetration was limited to less than 5% of total plasma concentrations, although CSF exposure was about 30% of the free drug exposure in plasma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The plasma and cerebrospinal fluid pharmacokinetics of erlotinib and its active metabolite (OSI-420) after intravenous administration of erlotinib in non-human primates. Meany, HJ., Fox, E., McCully, C., et al.[2015]

In a case study of a 32-year-old patient with advanced non-small cell lung cancer (NSCLC) and brain metastases, erlotinib was shown to accumulate in the brain metastases, indicating its potential effectiveness in treating these lesions.

Post-treatment imaging revealed regression of both the brain metastases and the primary lung tumor, suggesting that erlotinib can lead to significant therapeutic responses in patients with EGFR mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erlotinib accumulation in brain metastases from non-small cell lung cancer: visualization by positron emission tomography in a patient harboring a mutation in the epidermal growth factor receptor. Weber, B., Winterdahl, M., Memon, A., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

A translational model-based approach to inform the choice of the dose in phase 1 oncology trials: the case study of erdafitinib. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Erdafitinib: First Global Approval. [2020]

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

Central Nervous System Outcomes of Lazertinib Versus Gefitinib in EGFR-Mutated Advanced NSCLC: A LASER301 Subset Analysis. [2023]

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

Phase II trial of gefitinib in recurrent glioblastoma. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Quality-of-life benefits and evidence of antitumour activity for patients with brain metastases treated with gefitinib. [2018]

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

Erdafitinib-Induced Secondary Maculopathy. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Erlotinib for the treatment of brain metastases in non-small cell lung cancer. [2018]

8. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety of erlotinib and its metabolite OSI-420 in infants and children with primary brain tumors. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

The plasma and cerebrospinal fluid pharmacokinetics of erlotinib and its active metabolite (OSI-420) after intravenous administration of erlotinib in non-human primates. [2015]

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

Erlotinib accumulation in brain metastases from non-small cell lung cancer: visualization by positron emission tomography in a patient harboring a mutation in the epidermal growth factor receptor. [2022]