Ignite Creation Date:
2024-05-05 @ 9:21 PM
Last Modification Date:
2024-10-26 @ 10:02 AM
Study NCT ID:
NCT00863122
Status:
COMPLETED
Last Update Posted:
2021-01-12
First Post:
2009-03-13
Brief Title:
Concentration and Activity of Lapatinib in Vestibular Schwannomas
Sponsor:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Organization:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Overview
Official Title:
Exploration and Estimation of Intratumoral Concentration and Activity of Lapatinib in Vivo in Vestibular Schwannomas
Status:
COMPLETED
Status Verified Date:
2020-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Tumors can grow on the auditory nerves and can cause hearing loss A common type of tumor that does this is a vestibular schwannoma VS or acoustic neuroma These tumors are not cancerous Most often people have only one VS Occasionally people have more than one VS and may have a condition called neurofibromatosis type 2 NF2
Because VS can cause hearing loss many people with VS will have treatment to preserve their hearing This treatment usually involves surgery or radiation therapy There are risks to these procedures and sometimes they do not work to prevent hearing loss Because surgery and radiation have risks and are not able to help everyone with VS other methods of treatment are being explored One area of exploration is looking to see if there is a drug that can be taken that might prevent the VS from growing larger and causing hearing loss and might possibly even cause the VS to shrink in size
This study is exploring whether a drug that is approved by the FDA and is currently used to treat breast cancer might also work to treat VS This study will measure the amount of drug that travels from the bloodstream and arrives at the tumor This drug is safe and has few side effects If this drug is shown to reach the tumor it might be used in the future to treat VS without needing surgery or radiation
This study is recruiting people who are having surgery for VS If you are going to have surgery to treat a VS you may be eligible to participate
Because VS can cause hearing loss many people with VS will have treatment to preserve their hearing This treatment usually involves surgery or radiation therapy There are risks to these procedures and sometimes they do not work to prevent hearing loss Because surgery and radiation have risks and are not able to help everyone with VS other methods of treatment are being explored One area of exploration is looking to see if there is a drug that can be taken that might prevent the VS from growing larger and causing hearing loss and might possibly even cause the VS to shrink in size
This study is exploring whether a drug that is approved by the FDA and is currently used to treat breast cancer might also work to treat VS This study will measure the amount of drug that travels from the bloodstream and arrives at the tumor This drug is safe and has few side effects If this drug is shown to reach the tumor it might be used in the future to treat VS without needing surgery or radiation
This study is recruiting people who are having surgery for VS If you are going to have surgery to treat a VS you may be eligible to participate
Detailed Description:
Neurofibromatosis type 2 NF2 is a rare autosomal dominant genetic disorder with an incidence of approximately 140000 The most common tumor type in NF2 is vestibular schwannoma and the majority of NF2 patients develop progressive hearing loss in adolescence or young adulthood due to bilateral vestibular schwannoma VS In addition to hearing loss VS can cause significant morbidity and in some cases mortality due to brain stem compression
Currently the only accepted modality for treatment of VS in patients with NF2 is surgical resection Although surgical resection is effective at tumor reduction it is often associated with morbid complications such as hearing loss facial palsy CSF leaks chronic headache and infection In addition the tumors often recur after surgery Radiation therapy RT has been proposed as an alternative however its safety in the NF2 population has not been established and there is concern about long term efficacy For a distinct population of NF2 patients surgery and RT at not feasible and no additional therapy is currently available Hence a systemic therapy is needed
Sporadic VS are common with roughly 3000 new cases per year in the United States and a growing incidence in recent years These tumors cause unilateral hearing loss tinnitus and vertigo The primary treatment modality for these tumors is surgical resection or radiosurgery Surgery is associated with the same complications listed above for NF2-related VS Hence RT is often offered in place of surgery Although considered safe in sporadic VS it may not have good long term efficacy and may complicate future procedures Again a systemic therapy that could control tumor progression obviating the need for an invasive procedure is needed
As the understanding of tumor molecular biology continues to advance there are an increasing number of attractive targets for VS growth inhibition EGFR and ErbB2 have been identified as important targets for VS In a study of 21 sporadic and 17 NF2-related VS samples both EGFR and ErbB2 were found to be upregulated in the majority of tumors In addition an anti-ErbB2 monoclonal antibody reduced schwannoma cell proliferation in vitro Collectively this data suggests that abnormal signaling via EGFR and ErbB2 is a major contributor to tumor growth and progression in both sporadic and NF2-related VS and that inhibition of this signaling pathway can result in decreased tumor growth Although agents targeting these pathways are commercially available there is little pre-clinical data to assist in prioritizing which agents to advance to clinical trials Given the relative rarity of the disorder and the enormous patient financial and time commitments an efficacy study requires there is a need to carefully select agents for testing that have the best chance of success
In this trial we propose to assess the delivery of lapatinib a commercially available inhibitor of ErbB2 and EGFR to VS via tissue sampling at the time of clinically indicated surgery Demonstrating that lapatinib reaches meaningful intratumoral concentrations is important data to recommend this drug above other small molecule inhibitors for efficacy trials for VS The primary objective is to determine the steady state concentration of lapatinib in VS in patients with NF2 and in patients with sporadic VS Patient who are planning to have surgical resection of their tumor for clinical indications will be given lapatinib for 15 days prior to resection At the time of resection VS tissue will be assessed for drug concentration and molecular markers of drug activity
Demonstrating that lapatinib reaches meaningful concentrations within VS would support selecting this agent for investigation in efficacy studies for VS and tissue-based molecular studies will provide corollary information about the behavior of VS in general and about lapatinib specifically in VS tissue This may further our understanding of the pathophysiology of VS the similarities and differences between NF2-related and sporadic VS and inform the design of subsequent efficacy trials
Currently the only accepted modality for treatment of VS in patients with NF2 is surgical resection Although surgical resection is effective at tumor reduction it is often associated with morbid complications such as hearing loss facial palsy CSF leaks chronic headache and infection In addition the tumors often recur after surgery Radiation therapy RT has been proposed as an alternative however its safety in the NF2 population has not been established and there is concern about long term efficacy For a distinct population of NF2 patients surgery and RT at not feasible and no additional therapy is currently available Hence a systemic therapy is needed
Sporadic VS are common with roughly 3000 new cases per year in the United States and a growing incidence in recent years These tumors cause unilateral hearing loss tinnitus and vertigo The primary treatment modality for these tumors is surgical resection or radiosurgery Surgery is associated with the same complications listed above for NF2-related VS Hence RT is often offered in place of surgery Although considered safe in sporadic VS it may not have good long term efficacy and may complicate future procedures Again a systemic therapy that could control tumor progression obviating the need for an invasive procedure is needed
As the understanding of tumor molecular biology continues to advance there are an increasing number of attractive targets for VS growth inhibition EGFR and ErbB2 have been identified as important targets for VS In a study of 21 sporadic and 17 NF2-related VS samples both EGFR and ErbB2 were found to be upregulated in the majority of tumors In addition an anti-ErbB2 monoclonal antibody reduced schwannoma cell proliferation in vitro Collectively this data suggests that abnormal signaling via EGFR and ErbB2 is a major contributor to tumor growth and progression in both sporadic and NF2-related VS and that inhibition of this signaling pathway can result in decreased tumor growth Although agents targeting these pathways are commercially available there is little pre-clinical data to assist in prioritizing which agents to advance to clinical trials Given the relative rarity of the disorder and the enormous patient financial and time commitments an efficacy study requires there is a need to carefully select agents for testing that have the best chance of success
In this trial we propose to assess the delivery of lapatinib a commercially available inhibitor of ErbB2 and EGFR to VS via tissue sampling at the time of clinically indicated surgery Demonstrating that lapatinib reaches meaningful intratumoral concentrations is important data to recommend this drug above other small molecule inhibitors for efficacy trials for VS The primary objective is to determine the steady state concentration of lapatinib in VS in patients with NF2 and in patients with sporadic VS Patient who are planning to have surgical resection of their tumor for clinical indications will be given lapatinib for 15 days prior to resection At the time of resection VS tissue will be assessed for drug concentration and molecular markers of drug activity
Demonstrating that lapatinib reaches meaningful concentrations within VS would support selecting this agent for investigation in efficacy studies for VS and tissue-based molecular studies will provide corollary information about the behavior of VS in general and about lapatinib specifically in VS tissue This may further our understanding of the pathophysiology of VS the similarities and differences between NF2-related and sporadic VS and inform the design of subsequent efficacy trials
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NA_00020841 | None | None | None |