Treatment With Dasatinib in Patients With Acral Lentiginous, Mucosal, or Chronic Sun-damaged Melanoma

This study has been terminated.
(Slow accrual.)
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01092728
First received: March 23, 2010
Last updated: August 19, 2014
Last verified: August 2014
  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:

  1. To assess the safety and tolerability of dasatinib in this patient population
  2. 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
  3. To assess the secondary mutations that may account for resistance to dasatinib therapy

    Completely Resectable Acral, Chronic Sun-damaged (CSD), and Mucosal Melanoma:

  4. To assess the median time to recurrence and overall survival of patients with completely resectable acral, CSD, and mucosal melanoma treated with dasatinib
  5. 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
  6. 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:

  7. To assess the response rate, progression free survival, and overall survival of patients with acral, CSD, and mucosal melanoma treated with dasatinib
  8. 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
  9. 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
Procedure: Surgical Resection
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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • 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.


Enrollment: 19
Study Start Date: March 2011
Study Completion Date: August 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group 1: Completely Resectable
Surgical Resection Day 1 with 100 mg Dasatinib daily for 7 days. About 6 weeks after surgery, continue daily Dasatinib up to 13 cycles of 4 weeks (adjuvant treatment).
Drug: Dasatinib
100 mg daily.
Other Names:
  • BMS-354825
  • Sprycel
Active Comparator: Group 2: Unresectable
100 mg Dasatinib daily continued up to 13 cycles of 4 weeks
Drug: Dasatinib
100 mg daily.
Other Names:
  • BMS-354825
  • Sprycel
Procedure: Surgical Resection
Complete surgical resection of tumor(s).

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 18-Fluoro-deoxyglucose positron emission tomography (FDG-PET) (with or without computed tomography (CT)) defined as having a maximum standardized uptake value (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. Eastern Cooperative Oncology Group (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 (aspartate transaminase, alanine transaminase (AST, ALT) ) </= 2.5 times the institutional ULN, 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 human chorionic gonadotropin (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 Health Insurance Portability and Accountability Act (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 corrected QT interval (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 (</= 3 months) significant gastrointestinal bleeding.
  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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01092728

Locations
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Bristol-Myers Squibb
Investigators
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, NCI-2011-00468
Study First Received: March 23, 2010
Last Updated: August 19, 2014
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 September 30, 2014