Lapatinib in Stage IV Melanoma With ERBB4 Mutations
- Studies of melanoma tumor samples have shown that tumor cells from approximately 20 percent of melanoma patients contain a specific mutation of a gene involved in making a protein called ERBB4, and that changes in this gene have been associated with cancer. Lapatinib, a drug that is currently approved for the treatment of breast cancer, has been shown in the laboratory to significantly slow the growth of melanoma cells that contain this specific ERBB4 gene mutation. Researchers are interested in determining whether lapatinib can be effective against melanoma in individuals who have the ERBB4 mutation.
- To evaluate the safety and effectiveness of lapatinib as a treatment for melanoma with ERBB4 mutation that has not responded to standard therapy.
- Individuals at least 18 years of age who have stage 4 melanoma that has not responded to standard therapy.
- Participants will be screened with a full physical examination and medical history, as well as tests of tumor tissue taken from previous surgeries or biopsies or from a new biopsy that will be conducted before the start of the study. Test results to determine eligibility will be available within about 2 weeks.
- Participants will take four lapatinib tablets daily (two in the morning, 1 hour before or after breakfast and two in the evening, 1 hour before or after dinner) during every 28-day cycle of treatment. Participants will keep a medication diary to record tablets taken and any side effects from the medication.
- After the first 2 weeks, and every 2 to 4 weeks afterward for the first 12 weeks, participants will have clinic visits with blood samples and other tests to determine if lapatinib is causing their disease to shrink or be controlled. If the disease has not progressed, participants will continue to receive a new lapatinib supply every 28 days for up to 2 years (27 cycles), and will continue to have regular clinic visits to monitor the progress of treatment.
- When tumor tissue is easily accessible and can be easily biopsied, researchers will collect two additional biopsies, one after 2 weeks of treatment and one after 12 weeks of treatment....
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Lapatinib for the Treatment of Stage IV Melanoma Harboring ERBB4 Mutations|
- Number of Participants With a Partial Response (PR) and Complete Response (CR) to Lapatinib Who Have Metastatic Melanoma Harboring ERBB4 Mutations. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]The number of participants with a partial response and complete response is defined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progressions.
- Number of Participants With Adverse Events [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
|Study Start Date:||December 2010|
|Study Completion Date:||November 2013|
|Primary Completion Date:||November 2013 (Final data collection date for primary outcome measure)|
|Experimental: Group A||
500 mg PO (orally) twice a day for 28 days (1 cycle). Up to 27 cycles allowed if response seen.
- Patients with stage IV melanoma have few available treatment options and an overall poor prognosis.
- 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 mutations
- 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 Eastern Cooperative Oncology Group (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 follow-up.
- 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 (Partial Response (PR) + Complete Response (CR)) that can rule out 10% (p0=0.10) in favor of an improved response rate of 30% (p1=0.30).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01264081
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Udo Rudloff, M.D.||National Cancer Institute (NCI)|