Lapatinib in Stage IV Melanoma With ERBB4 Mutations
| Status: | Terminated |
|---|---|
| Conditions: | Skin Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | December 2010 |
| End Date: | November 2013 |
A Phase II Study of Lapatinib for the Treatment of Stage IV Melanoma Harboring ERBB4 Mutations
Background:
- 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.
Objectives:
- To evaluate the safety and effectiveness of lapatinib as a treatment for melanoma with
ERBB4 mutation that has not responded to standard therapy.
Eligibility:
- Individuals at least 18 years of age who have stage 4 melanoma that has not responded to
standard therapy.
Design:
- 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....
- 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.
Objectives:
- To evaluate the safety and effectiveness of lapatinib as a treatment for melanoma with
ERBB4 mutation that has not responded to standard therapy.
Eligibility:
- Individuals at least 18 years of age who have stage 4 melanoma that has not responded to
standard therapy.
Design:
- 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....
Background:
- 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.
Objectives:
Primary Objectives:
-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.
Secondary Objectives:
- 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
Eligibility:
- 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.
Design:
- 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).
- 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.
Objectives:
Primary Objectives:
-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.
Secondary Objectives:
- 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
Eligibility:
- 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.
Design:
- 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).
- INCLUSION CRITERIA:
- Patients must have histologically confirmed stage IV cutaneous melanoma.
- Patients must have measurable disease defined by Response Evaluation Criteria in
Solid Tumors (RECIST) 1.1. Measurable disease is defined as at least one lesion that
can be accurately measured in at least one dimension (longest diameter to be
recorded). Each lesion must be greater than 10 mm when measured by computed
tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical
exam; or greater than 20 mm when measured by chest x-ray. Lymph nodes must be greater
than 15 mm in short axis when measured by CT or MRI.
- Patients must have no more than two oncogenic somatic ERBB4 mutations detected in one
of the 28 exons of the ERBB4 gene analyzed from the tumor and which is not present in
the matched normal deoxyribonucleic acid (DNA) as confirmed by sequence analysis of
tumor genomic DNA derived from any biopsy specimen obtained at the participating
clinical sites. Sequence analysis will be performed at the National Institutes of
Health (NIH) Clinical Molecular Profiling Core, a Clinical Laboratory Improvement
Amendments (CLIA)-certified laboratory.
Note: Patients with 3 or more mutations in their ERBB4 gene may have an increased
resistance to lapatinib and are not eligible for lapatinib treatment
- Patients must not have had chemotherapy, molecular therapy with B-RAF, mouse
embryonic fibroblast (MEK), or c-kit inhibitors, hormonal therapy, radiation therapy,
or biological therapy for at least 4 weeks prior to starting study medication.
Patients who received mitomycin C, nitrosoureas, anti-cytotoxic T-lymphocyte antigen
4 (CTLA-4), or carboplatin must be 6 weeks from the last administration of therapy.
Patients must have recovered from any acute toxicity related to prior therapy or
surgery, to a grade 1 or less unless specified.
- Patients with no more than 3 intracranial metastases, which have been definitively
treated by surgery or radiation therapy may be eligible for study provided there is
no evidence of active disease for at least 2 months and no requirement for
anticonvulsant therapy or steroids following treatment.
- Age greater than or equal to 18 years.
Note: Because no dosing or adverse event data are currently available on the use of
lapatinib in patients less than 18 years of age, children are excluded from this study but
will be eligible for future pediatric single-agent trials, if applicable.
- Life expectancy of greater than 3 months.
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1
(Karnofsky greater than or equal to 70%).
- Patients must have normal organ and marrow function as defined below:
- absolute neutrophil count greater than or equal to 1,500/mcL
- platelets greater than or equal to 100,000/mcL
- total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase
(SGOT))/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase
(SGPT)) less than or equal to 3 times institutional upper limit of normal
- creatinine less than or equal to institutional upper limit of normal
OR
--creatinine clearance greater than or equal to 60 mL/min/1.73 m^2 for patients with
creatinine levels above institutional normal.
- Patients must be willing to return to the Clinic for follow-up visits.
- Women of childbearing potential must have a negative beta-human chorionic
gonadotropin (HCG) (serum or urine) within 14 days prior to study treatment and must
be willing to practice effective birth control to prevent pregnancy while receiving
treatment and for four months after treatment is discontinued. All males of child
fathering potential must also be willing to practice effective birth control.
Note: Lapatinib is a tyrosine kinase inhibitor with the potential for teratogenic or
abortifacient effects. Because there is an unknown but potential risk for adverse events
in nursing infants secondary to treatment of the mother with lapatinib, breastfeeding
should be discontinued if the mother is treated with lapatinib. Should a woman become
pregnant or suspect she is pregnant while she or her partner is participating in this
study, the patient should inform the treating physician immediately.
- Ability to understand and the willingness to sign the Informed Consent Document.
- Patients who agree to participate in the pharmacokinetics (PK) portion of the study
must be able to swallow lapatinib tablets for the duration of the PK studies.
EXCLUSION CRITERIA:
- Patients may not be currently receiving any other investigational agents.
- Patients may not have received prior treatment with tyrosine kinase inhibitors (e.g.,
lapatinib erlotinib, or gefitinib).
- Patients currently receiving any medication known to induce/inhibit cytochrome P450
3A4 (CYP3A4) as listed in Appendix D, which in the opinion of the principal
investigator, would make the administration of study drug hazardous. Note: patients
receiving any strong or moderate CYP3A4 inhibitors will be excluded.
- Patients with active hepatic or biliary disease (with exception of patients with
Gilberts syndrome, asymptomatic gallstones, liver metastases or stable chronic liver
disease per investigator assessment)
- Patients with uncontrolled intercurrent illness including, but not limited to,
ongoing or active infection, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
limit compliance with study requirements.
- Human immunodeficiency virus (HIV)-positive patients on antiretroviral therapy are
excluded because most antiretrovirals are strong or moderate CYP3A4 inhibitors.
- Any underlying medical condition which, in the opinion of the principal investigator,
will make the administration of study drug hazardous or obscure the interpretation of
adverse events
- Patients with any other concurrent malignancy, except for the following:
- adequately treated basal or squamous cell skin cancer, superficial bladder
cancer, carcinoma in situ of the cervix, or any other cancer from which the
patient has been disease-free for five (5) years or more.
INCLUSION OF WOMEN AND MINORITIES:
Both men and women and members of all races and ethnic groups are eligible for this trial.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Click here to add this to my saved trials
