Treatment With Dasatinib in Patients With Acral Lentiginous, Mucosal, or Chronic Sun-damaged Melanoma
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Purpose
The goal of this clinical research study is to compare how the drug Sprycel (dasatinib) can help to control the tumor in patients whose tumor has a gene abnormality known as a "CKIT mutation" to patients whose tumor does not have a CKIT mutation. The safety of this drug will also be studied.
Objectives:
Primary Objectives:
1. To compare the biological response of tumors harboring exon 11 or 13 KIT mutations versus tumors without exon 11 or 13 KIT mutations from patients with acral, or mucosal melanomas after treatment with dasatinib.
Secondary Objectives:
- To assess the safety and tolerability of dasatinib in this patient population
- To evaluate molecular changes of tumors harboring exon 11 or 13 KIT mutations versus tumors without KIT exon 11 or 13 mutations from patients with acral or mucosal melanomas after treatment with dasatinib by assessing apoptosis, autophagy and cell proliferation markers
To assess the secondary mutations that may account for resistance to dasatinib therapy
Completely Resectable Acral, CSD, and Mucosal Melanoma:
- To assess the median time to recurrence and overall survival of patients with completely resectable acral, CSD, and mucosal melanoma treated with dasatinib
- To assess whether FDG-avidity and KIT phosphorylation responses after treatment with dasatinib predicts prolonged time to recurrence and/or overall survival in patients with completely resectable acral, CSD, and mucosal melanomas
To assess whether exon 11 or 13 KIT mutation status predicts prolonged time to recurrence and/or overall survival in patients with completely resectable acral, CSD, and mucosal melanomas treated with dasatinib
Not Completely Resectable Acral, CSD, and Mucosal Melanoma:
- To assess the response rate, progression free survival, and overall survival of patients with acral, CSD, and mucosal melanoma treated with dasatinib
- To assess whether FDG-avidity and KIT phosphorylation responses after treatment with dasatinib predicts response rate, progression free survival, and/or overall survival in patients with acral, CSD, and mucosal melanomas
- To assess whether exon 11 or 13 KIT mutation status predicts response rate, progression free survival, and/or overall survival in patients with acral, CSD, and mucosal melanomas
| Condition | Intervention | Phase |
|---|---|---|
|
Melanoma |
Drug: Dasatinib |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase II Study of Biological Response to Dasatinib Treatment in Patients With Acral Lentiginous, Mucosal, or Chronic Sun-damaged Melanoma |
- Comparison of Biologic Response of Patient Tumors with and without Exon 11 or 13 KIT Mutations [ Time Frame: Baseline to 7 Days ] [ Designated as safety issue: Yes ]Biologic response defined as either a (complete or partial) metabolic response or a molecular response after 7 days of dasatinib treatment.
| Estimated Enrollment: | 30 |
| Study Start Date: | March 2011 |
| Estimated Primary Completion Date: | May 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Group 1: Completely Resectable
100 mg Dasatinib daily x 7 days
|
Drug: Dasatinib
100 mg daily x 7 days
Other Names:
|
|
Active Comparator: Group 2: Unresectable
100 mg Dasatinib daily x 7 days
|
Drug: Dasatinib
100 mg daily x 7 days
Other Names:
|
Show Detailed Description
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
- (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.
- 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.
- 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.
- 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.
- Age >/= 18 years.
- ECOG performance status 0 or 1.
- Adequate Organ Function: a. Total bilirubin < 2.0 times the institutional Upper Limit of Normal (ULN), b.Hepatic enzymes (AST, ALT ) </= 2.5 times the institutional ULN, c. Serum Creatinine < 1.5 time the institutional ULN, d.Neutrophil count >/= 1500; Platelets >/= 75,000;
- Ability to take oral medication (dasatinib must be swallowed whole)
- 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.
- 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.
- Signed written informed consent including a HIPAA form according to institutional guidelines
Exclusion Criteria:
- No other malignancy which required radiotherapy or systemic treatment within the past 5 years.
- Concurrent medical condition which may increase the risk of toxicity, including: a. Pleural or pericardial effusion of any grade.
- 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.
- 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 (</= 3 months) significant gastrointestinal bleeding.
- 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.
- 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,
- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness
- 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
- 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.
- Patients with melanoma harboring BRAF mutation. If BRAF mutation is not known at the time of screening, patients will still be eligible
Contacts and Locations| Contact: Kevin B. Kim, MD, BA | 713-792-2921 |
| United States, Texas | |
| UT MD Anderson Cancer Center | Recruiting |
| Houston, Texas, United States, 77030 | |
| Principal Investigator: Kevin B. Kim, MD, BA | |
| Study Chair: | Kevin B. Kim, MD, BA | UT MD Anderson Cancer Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT01092728 History of Changes |
| Other Study ID Numbers: | 2009-0447 |
| Study First Received: | March 23, 2010 |
| Last Updated: | February 18, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by M.D. Anderson Cancer Center:
|
Acral lentiginous melanoma Mucosal melanoma Chronic sun-damaged melanoma Surgically removed tumor |
biopsied Sprycel Dasatinib CKIT mutation |
Additional relevant MeSH terms:
|
Melanoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Nerve Tissue |
Nevi and Melanomas Dasatinib Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions |
ClinicalTrials.gov processed this record on June 17, 2013