A Phase II Study of Biological Response to Dasatinib Treatment in Patients With Acral Lentiginous, Mucosal, or Chronic Sun-damaged Melanoma
18 Years
N/A
Both
Melanoma
Trial Information
A Phase II Study of Biological Response to Dasatinib Treatment in Patients With Acral Lentiginous, Mucosal, or Chronic Sun-damaged Melanoma
The Study Drug:
Dasatinib is designed to change the function of genes. By changing the function of these
genes, it may prevent cancer from growing and spreading.
Study Groups:
If you are found to be eligible to take part in this study, you will be placed into one of
two groups depending on if the disease can be removed by surgery on or not. Group 1 will be
patients who have melanoma that can be removed by surgery. Group 2 will be patients who
have melanoma that cannot be completely removed by surgery.
Study Drug Administration:
For this study, every 4 weeks is a study "cycle."
Dasatinib pills will be taken by mouth with a full glass (8 ounces) of water with or without
a meal. The pills should not be crushed or cut, they should be swallowed whole.
If you are in Group 1, you will take 2 dasatinib pills 1 time every day, for 7 days before
your already-scheduled surgery. About 6 weeks after surgery (depending on how long it takes
you to recover) you will begin taking 2 dasatinib pills 1 time every day for up to 13 cycles
as long as you tolerate it and the disease does not come back.
If you are in Group 2, you will take 2 dasatinib pills 1 time every day, for 7 days before
your already-scheduled biopsy on Day 8 (+/1 business day) of Cycle 1. Within 5 days after
the biopsy, you will begin taking 2 dasatinib pills 1 time every day for up to 13 cycles, as
long as you tolerate it and the disease does not come back.
Both groups will be given a pill chart to fill out at home to record when you take the study
drug, and how many pills you take each time. You will need to bring the pill chart to every
study visit for the study doctor to review. You will also need to bring the pill bottles to
each study visit.
Group 1 Study Visits:
After the screening tests have been complete, and before you start taking the study drug,
the following procedures will be performed:
- Your weight and vital signs will be measured.
- You will be asked about any drugs you may be taking.
- Your performance status will be recorded.
After 7 days of taking the study drug, and before surgery, the following procedures will be
performed:
- You will have a physical exam, including a measurement of your weight and vital signs.
- Blood (about 1 tablespoon) will be drawn for routine tests.
- Your performance status will be recorded.
- You will be asked about any other drugs you may be taking.
- You will have an ECG to check your heart function.
- You will have a PET scan to check the status of the disease.
About 6 weeks after surgery, when you begin taking the study drug on Cycle 1, the following
tests and procedures will be performed on Day 1 of each cycle:
- Blood (about 1 tablespoon) will be drawn for routine tests.
- You will have a physical exam, including a measurement of your weight and vital signs.
- Your performance status will be recorded.
- You will be asked about any other drugs you may be taking, and any side effects you may
be experiencing.
On Day 15 of Cycle 1 only, the following tests and procedures will be performed:
- Blood (about 1 tablespoon) will be drawn for routine tests.
- You will have a physical exam, including a measurement of your weight and vital signs.
- Your performance status will be recorded.
- You will be asked about any other drugs you may be taking, and any side effects you may
be experiencing.
Every 12 weeks while you are receiving treatment, the following tests and procedures will be
performed:
- An ECG will be performed to check your heart function.
- You will have a CT scan or MRI scan of the chest, abdomen, and pelvis to check the
status of the disease.
Group 2 Study Visits:
After the screening tests have been complete, and before you start taking the study drug,
the following procedures will be performed:
- You will have a measurement of your vital signs including your weight.
- You will be asked about any drugs you may be taking.
- Your performance status will be recorded.
After 7 days of taking the study drug, and before the biopsy, the following procedures will
be performed:
- You will have a physical exam, including a measurement of your weight and vital signs.
- Blood (about 1 tablespoon) will be drawn for routine tests.
- Your performance status will be recorded.
- You will be asked about any other drugs you may be taking.
- You will have an ECG to check your heart function.
- You will have a PET scan to check the status of the disease.
About 5 days after the biopsy, you will begin taking the study drug again for 3 more weeks
to complete Cycle 1. On Day 15 of Cycle 1 only, the following tests and procedures will be
performed:
- Blood (about 1 tablespoon) will be drawn for routine tests.
- You will have a physical exam including a measurement of your weight and vital signs.
- Your performance status will be recorded.
- You will be asked about any other drugs you may be taking, and any side effects you may
be experiencing.
The following tests and procedures will be performed on Day 1 of each cycle starting with
Cycle 2:
- Blood (about 1 tablespoon) will be drawn for routine tests.
- You will have a physical exam, including a measurement of your weight and vital signs.
- Your performance status will be recorded.
- You will be asked about any other drugs you may be taking, and any side effects you may
be experiencing.
Every 12 weeks while you are receiving treatment, the following tests and procedures will be
performed:
- An ECG will be performed to check your heart function.
- You will have a CT scan or MRI scan of the chest, abdomen, and pelvis to check on the
status of the disease.
Length of Study:
You will continue to take the study drug for up to 13 cycles. You will be taken off study
early if you experience intolerable side effects, the disease returns (Group 1 only), the
disease gets worse (Group 2 only), or if the study doctor thinks it is in your best
interest.
If you are in Group 2, and you are benefiting from the treatment, you may be allowed to
continue to receive treatment with the study drug after you have completed the 12 study
cycles. The study doctor will discuss this option with you in more detail.
End-of-Study Visit:
Within 30 days after the last dose of study drug, you will have an end-of-study visit, at
which the following tests and procedures will be performed:
- Blood (about 1 tablespoon) will be drawn for routine tests.
- An ECG will be performed to check your heart function.
- You will have a CT scan or MRI scan of your chest, abdomen, and pelvis performed to
check the status of the disease.
- You will have a physical exam, including a measurement of your weight and vital signs.
- Your performance status will be recorded.
- You will be asked about any other drugs you may be taking, and any side effects you may
be experiencing.
Follow-Up Visits:
After your participation on this study is complete, you will have follow-up visit every 3
months and you will be asked about your health status. If you do not come to the hospital
for a regularly scheduled clinic visit, you will receive a follow-up phone call. The phone
call should last about 15 minutes each time.
This is an investigational study. Dasatinib is FDA approved and commercially available for
the treatment of certain types of leukemia. The use of dasatinib to treat acral lentiginous
melanoma, mucosal melanoma, or chronic sun-damaged melanoma is investigational.
Inclusion Criteria:
1. Patients must have primary, recurrent or metastatic melanoma with one of the
following pathology or characteristics: i) acral lentiginous melanoma ii) mucosal
melanoma iii) any known KIT mutation.
2. (Continued 1) If 20 patients without tumors harboring exon 11 or 13 KIT mutation are
enrolled and treated before the completion of the patient accrual of 30, only those
with tumors harboring exon 11 or 13 KIT mutation will be enrolled. Likewise, if 10
patients with tumors harboring exon 11 or 13 KIT mutation are enrolled and treated
before the completion of the patient accrual of 30, only those without tumors
harboring exon 11 or 13 KIT mutation will then be enrolled.
3. Patients must have measurable disease by FDG-PET (with or without CT) defined as
having a SUVmax of 3 and SUVmax ofat least 2 fold greater than background.
4. Patients scheduled for FDG-PET should have uptake of the tracer in at least one
lesion (tumor-to-muscle ratio >2) in the baseline PET/CT scan in order to be eligible
for the follow-up FDG PET scans.
5. Patient must have surgically resectable melanoma lesion(s) or biopsiable lesion(s)
which are amenable to 2 separate biopsy procedures by a core needle or excision.
6. Age >/= 18 years.
7. ECOG performance status 0 or 1.
8. Adequate Organ Function: a. Total bilirubin < 2.0 times the institutional Upper Limit
of Normal (ULN), b.Hepatic enzymes (AST, ALT ) c. Serum Creatinine < 1.5 time the institutional ULN, d.Neutrophil count >/= 1500;
Platelets >/= 75,000;
9. Ability to take oral medication (dasatinib must be swallowed whole)
10. Concomitant Medications: a. Patient agrees to discontinue St. Johns Wort while
receiving dasatinib therapy (discontinue St. Johns Wort at least 5 days before
starting dasatinib), b.Patient agrees that IV bisphosphonates will be withheld for
the first 8 weeks of dasatinib therapy due to risk of hypocalcemia.
11. Women of childbearing potential (WOCBP) must have: a) A negative serum or urine
pregnancy test (sensitivity 25 IU HCG/L) within 72 hours prior to the start of study
drug administration b) Persons of reproductive potential must agree to use and
utilize an adequate method of contraception throughout treatment and for at least 4
weeks after study drug is stopped. Prior to study enrollment, women of childbearing
potential must be advised of the importance of avoiding pregnancy during trial
participation and the potential risk factors for an unintentional pregnancy.
12. Signed written informed consent including a HIPAA form according to institutional
guidelines
Exclusion Criteria:
1. No other malignancy which required radiotherapy or systemic treatment within the past
5 years.
2. Concurrent medical condition which may increase the risk of toxicity, including: a.
Pleural or pericardial effusion of any grade.
3. Cardiac Symptoms; any of the following should be considered for exclusion: a.
Uncontrolled angina, congestive heart failure or MI within (6 months), b. Diagnosed
congenital long QT syndrome, c. Any history of clinically significant ventricular
arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades
de pointes), d. Prolonged QTc interval on pre-entry electrocardiogram (> 480 msec)
[or > 500 msec for patients with a bundle branch block]), e. Subjects with
hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib
administration.
4. History of significant bleeding disorder unrelated to cancer, including: a. Diagnosed
congenital bleeding disorders (e.g., von Willebrand's disease), b. Diagnosed acquired
bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies), c.
Ongoing or recent (
5. Concomitant Medications, any of the following should be considered for exclusion: a.
Category I drugs that are generally accepted to have a risk of causing Torsades de
Pointes including: (Patients must discontinue drug 7 days prior to starting
dasatinib), I. quinidine, procainamide, disopyramide, II. amiodarone, sotalol,
ibutilide, dofetilide, III. erythromycin, clarithromycin, IV. chlorpromazine,
haloperidol, mesoridazine, thioridazine, pimozide V. cisapride, bepridil, droperidol,
methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl,
pentamidine, sparfloxacin, lidoflazine.
6. Women who: a. are unwilling or unable to use an acceptable method to avoid pregnancy
for the entire study period and for at least 4 weeks after cessation of study drug,
or, b. have a positive pregnancy test at baseline, or, c. are pregnant or
breastfeeding,
7. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
treatment of either a psychiatric or physical (e.g., infectious) illness
8. No active, untreated brain metastases. Patients with known brain metastases will be
included if the brain metastases have been treated and stable for at least 3 months
without the use of steroid
9. HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with dasatinib. In addition, these
patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy. Appropriate studies will be undertaken in patients
receiving combination antiretroviral therapy when indicated.
10. Patients with melanoma harboring BRAF mutation. If BRAF mutation is not known at the
time of screening, patients will still be eligible
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Comparison of Biologic Response of Patient Tumors with and without Exon 11 or 13 KIT Mutations
Outcome Description:
Biologic response defined as either a (complete or partial) metabolic response or a molecular response after 7 days of dasatinib treatment.
Outcome Time Frame:
Baseline to 7 Days
Safety Issue:
Yes
Principal Investigator
Kevin B. Kim, MD, BA
Investigator Role:
Study Chair
Investigator Affiliation:
UT MD Anderson Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
2009-0447
NCT ID:
NCT01092728
Start Date:
March 2011
Completion Date:
Related Keywords:
- Melanoma
- Acral lentiginous melanoma
- Mucosal melanoma
- Chronic sun-damaged melanoma
- Surgically removed tumor
- biopsied
- Sprycel
- Dasatinib
- CKIT mutation
- Melanoma
Name | Location |
|---|---|
| UT MD Anderson Cancer Center | Houston, Texas 77030 |
