Concentration and Activity of Lapatinib in Vestibular Schwannomas

• Status: Completed
• Trial end date: 2014-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

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

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.