Concentration and Activity of Lapatinib in Vestibular Schwannomas

NCT00863122 | Completed Early Phase 1 Results

• 2 other identifiers: J0867NA_00020841
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 7

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.

Conditions

Vestibular Schwannoma; NF2; Neurofibromatosis 2; Acoustic Neuroma; Auditory Tumor

Keywords

Lapatinib; Tykerb; EGFR inhibitor; ErbB2 inhibitor; Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Median Steady-state Lapatinib Plasma Concentrations at the Time of Surgical Resection

  Steady-state plasma concentrations of lapatinib (ng/mL) at time of surgery, 10-13 days from starting drug.

  At time of surgery, 10-13 days from starting drug.

• To Assess Whether Lapatinib Can Reach a Minimum Tumor Concentration Level of >3uM in VS After Oral Dosing.

  Count of tissue samples with lapatinib concentration \>3uM

  one year

Secondary Outcomes (4)

• Assess the Level of ErbB2 Phosphorylation in VS.

  at time of surgery

• Assess Markers of Tumor Proliferation and Cell Death in VS After Exposure to Lapatinib.

  At time of surgery

• Explore the Difference in the Concentration of Lapatinib Achieved in NF2-related Versus Idiopathic VS.

  one year

• Perform NF2 Gene Mutation Analysis Via Exon Scanning and MLPA as Well as Protein Expression in All VS and Explore Differences Between Sporadic and NF2 Related VS.

  at time of surgery

Study Arms (2)

lapatinib

EXPERIMENTAL

Subjects will receive lapatinib for 10 days prior to surgery for vestibular schwannoma resection.

Drug: lapatinib

control

NO INTERVENTION

Control subjects will not receive any intervention prior to surgery for vestibular schwannoma resection.

Interventions

lapatinib DRUG

1500 mg lapatinib by mouth per day for 10 days

Also known as: Tykerb

lapatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meet diagnostic criteria for NF2 including presence of bilateral VS or idiopathic VS without evidence of genetic syndrome.
• VS surgery determined clinically necessary by the treating physician and scheduled within 4 weeks.
• Normal cardiac left ventricular ejection fraction (LVEF) by multiple-gated acquisition (MUGA) scan or transthoracic echocardiogram.
• Karnofsky performance status 60% (i.e. the patient must be able to care for himself/herself with occasional help from others).
• Must have the following hematologic, renal and liver function: Absolute neutrophil count ≥ 1,000/mm³ (unsupported); platelet count ≥ 75,000/mm³ (unsupported); hemoglobin ≥ 8 g/dL (transfusion support allowed); Creatinine ≤ 1.5 times upper limit of normal (ULN) OR glomerular filtration rate ≥ 70 ml/min; Bilirubin ≤ 1.5 times ULN; ALT ≤ 2.5 times ULN.
• Be able to provide written informed consent.
• Any neurologic deficits must be stable for ≥ 1 week.
• Be able to swallow tablets.
• Subjects with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. Women of childbearing potential must have a negative pregnancy test.
• Suspend the use of P450 inducing or P450 suppressing agents for a minimum of 10 days prior to starting lapatinib.

You may not qualify if:

• Serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety.
• Pregnant or breast-feeding.
• Receiving concurrent therapy for their tumor (i.e. chemotherapeutics or investigational agents, radiation or immunotherapy) within 4 weeks of the first dose of the study drug.
• Concurrent or prior malignancy, other than curatively treated carcinoma-in-situ or basal cell carcinoma of the skin. Subjects who have been free of disease (any prior malignancy) for five years are eligible for this study.
• Received cytochrome P450-inducing anticonvulsants (EIADs; e.g., phenytoin, carbamazepine, phenobarbital, primidone, oxcarbazepine) or similar agents (e.g., rifampin) or P450 inhibiting agents (Ketoconazole, Itraconazole, Clarithromycin, Atazanavir, Indinavir, Nefazodone, Nelfinavir, Ritonavir, Saquinavir, Telithromycin, Voriconazole) within 10 days prior to starting lapatinib.
• Significant gastrointestinal disorder(s)(e.g., Crohn's disease, ulcerative colitis, extensive gastric resection).
• Neurologic deficits that are rapidly progressing.
• Known cardiac disease (either arrhythmia or congestive heart failure) requiring treatment.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• The Children's Tumor Foundation: collaborator
• GlaxoSmithKline: collaborator
• New York University: collaborator
• Ohio State University: collaborator
• House Research Institute: collaborator
• Washington University School of Medicine: collaborator
• Weill Medical College of Cornell University: collaborator
• Massachusetts General Hospital: collaborator

Study Sites (7)

House Reserach Institute

Los Angeles, California, 90057, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Washington University Medical Center

St Louis, Missouri, 63110, United States

Location

New York University Medical Center

New York, New York, 10016, United States

Location

Weil Cornell Medical College, New York Presbyterian Hospital

New York, New York, 10065, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Neuroma, Acoustic; Neurofibromatosis 2

Interventions

Lapatinib

Condition Hierarchy (Ancestors)

Neurilemmoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neuroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Cranial Nerve Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Peripheral Nervous System Neoplasms; Vestibulocochlear Nerve Diseases; Retrocochlear Diseases; Ear Diseases; Otorhinolaryngologic Diseases; Otorhinolaryngologic Neoplasms; Cranial Nerve Diseases; Nervous System Diseases; Neurofibromatoses; Neurofibroma; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

A total of 10 tissue and 11 plasma samples donated by participants receiving lapatinib and 2 tissue samples from control participants were lost from analysis due to freezer failure denaturing the samples. This substantially reduced the sample size.

Results Point of Contact

• Title: Jaishri Blakeley
• Organization: Johns Hopkins School of Medicine

jblakel3@jhmi.edu

410-955-6827

Study Officials

• Jaishri O Blakeley, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2009
• First Posted: March 17, 2009
• Study Start: June 1, 2009
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: January 12, 2021
• Results First Posted: November 26, 2018

Record last verified: 2020-12

Locations

US (7)