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

NCT01092728 | Terminated Phase 2 Results DMC

• 2 other identifiers: 2009-0447NCI-2011-00468
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to compare how the drug Sprycel (dasatinib) can help to control the tumor in Patients With Acral Lentiginous, Mucosal, or Chronic Sun-damaged Melanoma. The safety of this drug will also be studied. Objectives: Primary Objectives: 1\. To compare the biological response of tumors With and Without Resectable Tumors from patients with acral, or mucosal melanomas after treatment with dasatinib. Secondary Objectives:

1. 1.To assess the safety and tolerability of dasatinib in this patient population
2. 2.To assess the median time to recurrence and overall survival of patients with completely resectable acral, CSD, and mucosal melanoma treated with dasatinib
3. 3.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
4. 4.To assess the response rate, progression free survival, and overall survival of patients with acral, CSD, and mucosal melanoma treated with dasatinib
5. 5.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

Conditions

Melanoma

Keywords

Acral lentiginous melanoma; Mucosal melanoma; Chronic sun-damaged melanoma; Surgically removed tumor; biopsied; Sprycel; Dasatinib

Outcome Measures

Primary Outcomes (1)

• Biologic Response Evaluation of Tumors With and Without Resectable Tumors

  Biologic response defined as either (complete or partial) metabolic tumor response after 7 days dasatinib treatment by positron emission tomography (PET) scan, \>/= 25% decrease in Fluorodeoxyglucose (FDG) activity on PET without \>15% increase in tumoral Ki-67 expression or \>/=25% decrease in tumoral Ki-67 expression without \>15% increase in FDG activity on PET scan. Complete Metabolic Response (CMR): FDG-avidity all lesions reduced to background FDG-avidity level. Partial Metabolic Response (PMR): \>/=25% decrease in FDG-avidity as represented by change in mean Standardized Uptake Values (SUV) max. SUVmax measured by drawing region of interest slightly outside each lesion corresponding to those on CT image \& adjusted for body weight. Measureable disease by PET scan defined as lesions that can be determined to have FDG-avidity of SUVmax of 3 and 2 x background. PR or CR confirmatory disease assessment performed \>4 weeks (28 days) after criteria for response first met.

  Assessment at 7 Days with confirmatory disease assessment performed no less than 4 weeks (28 days) afterwards

Secondary Outcomes (1)

• Progression-Free Survival

  Evaluated every 2 cycles (8 weeks) until disease progression or last follow-up, up to two years

Study Arms (2)

Group 1: Completely Resectable

ACTIVE COMPARATOR

Dasatinib 100 mg daily for 7 days and then surgical resection on Day 8. Afterwards, Dasatinib 100 mg daily will be administered for a total of 12 months/12 cycles (1 cycle = 4 weeks of treatment).

Drug: Dasatinib; Procedure: Surgical Resection

Group 2: Unresectable

ACTIVE COMPARATOR

100 mg Dasatinib daily continued up to 12 months/12 cycles (1 cycle = 4 weeks of treatment).

Drug: Dasatinib

Interventions

Dasatinib DRUG

100 mg daily.

Also known as: BMS-354825, Sprycel

Group 1: Completely Resectable; Group 2: Unresectable

Surgical Resection PROCEDURE

Complete surgical resection of tumor(s).

Group 1: Completely Resectable

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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.
• 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.
• Eastern Cooperative Oncology Group (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 (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;
• 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 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.
• Signed written informed consent including a Health Insurance Portability and Accountability Act (HIPAA) form according to institutional guidelines

You may not qualify if:

• 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.
• 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.
• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Melanoma

Interventions

Dasatinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Results Point of Contact

• Title: Kevin Kim, MD/Melanoma Medical Oncology
• Organization: The University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

1-877-MDA-6789

Study Officials

• Kevin B. Kim, MD, BA

  UT MD Anderson Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2010
• First Posted: March 25, 2010
• Study Start: March 1, 2011
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: September 5, 2016
• Results First Posted: September 5, 2016

Record last verified: 2016-07

Locations

US (1)