A Phase II Study of Lapatinib for the Treatment of Stage IV Melanoma Harboring ERBB4 Mutations
- Patients with stage IV melanoma have few available treatment options and an overall
- Pre-clinical evidence suggests that lapatinib has activity against metastatic melanoma
harboring ERBB4 mutations.
-Determine the response rate to lapatinib administered as 500 mg orally twice daily on a
continuous schedule in patients with metastatic melanoma harboring ERBB4 mutations.
- To determine the progression free survival of patients with stage IV melanoma treated
with lapatinib monotherapy.
- To evaluate the safety of lapatinib in patients with metastatic melanoma
- To determine the impact of additional genetic alterations on the response to lapatinib
in melanoma harboring ERBB4 mutations
- To develop a clinically applicable biomarker predictive of response to lapatinib in
patients with melanoma harboring ERBB4 mutations
- To determine the pharmacokinetics of lapatinib administered as 500 mg orally twice
daily on a continuous schedule in patients with metastatic melanoma harboring ERBB4
- Patients greater than or equal to 18 years of age with stage IV melanoma, who have
measurable disease and whose tumors express up to two ERBB4 gene mutations.
- Patient must be ECOG performance status of less than or equal to 1 and a life
expectancy of more than 3 months.
- Patients must have adequate organ function.
- Patients must not have had surgery, chemotherapy, hormonal therapy, radiation therapy,
or biological therapy for at least 4 weeks prior to starting study medication.
- Patients must not have an acute, critical illness.
- All patients who are sexually active and able to conceive will be required to use
contraception during treatment with lapatinib.
- Patients will be screened for the presence of ERBB4 gene mutations in their tumor and
only patients who harbor less than or equal to 2 ERBB4 mutations will be enrolled in
the treatment phase of the study.
- Lapatinib will be administered as an oral dose of 500 mg twice daily (in the morning
and evening) taken one hour before or after meals. Lapatinib will be given
continuously; one cycle equals 28 days. Course 1 equals cycle 1; all subsequent courses
are 8 weeks long (2 cycles). A patient may receive up to 27 cycles (14 courses).
- Up to 25 patients (allowing for a staged accrual of initially 16 patients who will
receive lapatinib and are evaluable after the 1st cycle) will be enrolled over 2-3
years and the trial will be completed over 3-5 years, allowing for completion of
- The primary objective of the trial will be to determine whether lapatinib monotherapy
in this setting is able to be associated with a response rate (PR +CR) that can rule
out 10% (p0=0.10) in favor of an improved response rate of 30% (p1=0.30).
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Response rate to lapatinib in patients with metastatic melanoma harboring ERBB4 mutations.
Udo Rudloff, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|
|Memorial Sloan Kettering Cancer Center||New York, New York 10021|
|Vanderbilt University||Nashville, Tennessee 37232-6305|