Clinical trial NCT00700882: Dasatinib in Treating Patients With Locally Advanced or Metastatic Mucosal Melanoma, Acral Melanoma, or Vulvovaginal Melanoma That Cannot Be Removed By Surgery
Official title: A Phase II Trial of Dasatinib in KIT-Positive Patients With Unresectable Locally Advanced or Stage IV Mucosal, Acral and Vulvovaginal Melanomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma (Skin)
Keywords: stage IV melanoma
acral melanoma
mucosal melanoma
vulvovaginal melanoma
stage III melanoma
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-06-19
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well dasatinib works in treating patients with locally advanced or metastatic mucosal melanoma or acral melanoma.

Detailed description: OBJECTIVES:

Primary

* To estimate the objective tumor response rate in patients with KIT-positive, unresectable, locally advanced or metastatic acral or mucosal melanoma treated with dasatinib monotherapy.

Secondary

* To estimate the response duration in patients treated with this drug.
* To estimate the progression-free survival of patients treated with this drug.
* To evaluate the safety profile of this drug in these patients.
* To evaluate the PDGFR expression and activation of Src family kinases in tumor samples and correlate these parameters with response to treatment.

OUTLINE: This is a multicenter study.

Patients receive oral dasatinib twice daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Tissue samples may be collected from some patients for correlative studies.

After completion of study therapy, patients are followed up periodically for up to 5 years.

Eligibility criteria: Inclusion Criteria for Pre-Registration (Step 0):

* Histologically or cytologically confirmed melanoma of 1 of the following subtypes:

  * Acral melanoma (defined as occurring on the palms, soles, or subungual sites)
  * Melanoma arising from the vagina and/or vulva
  * Melanoma arising on other mucosal surface (not vagina or vulva)
* Unresectable locally advanced or metastatic disease
* c-KIT mutation identified by polymerase chain reaction (PCR) and sequencing meeting 1 of the following criteria:

  * At least 1 mutation in exon 9, 11, 13, 17, or 18
  * At least 1 mutation in an exon not listed above and approved by central reviewer
* Metastatic tumor blocks are required for the evaluation of KIT mutations or amplifications
* Prior radiotherapy to a measurable lesion allowed provided there is radiographic evidence of progression of that lesion
* No other concurrent malignancies except basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, ductal or lobular carcinoma in situ of the breast, or other malignancies from which the patient has been continuously disease-free for ≥ 5 years
* ECOG performance status 0-1

Exclusion Criteria for Pre-Registration (Step 0):

* Prior treatment with targeted therapies directed to c-KIT/PDGFR (e.g., imatinib or sunitinib)
* Ocular melanoma
* Evidence of bleeding diathesis
* Clinically significant psychiatric illness or social situations that would limit compliance with study requirements
* Clinically significant cardiovascular disease including the following:

  * Myocardial infarction or ventricular tachyarrhythmia within 6 months
  * Prolonged QTc \>480 msec (Fridericia correction)
  * Ejection fraction less than institutional normal
  * Major conduction abnormality (unless a cardiac pacemaker is present)
  * Patients with any cardiopulmonary symptoms of unknown cause (e.g., shortness of breath, chest pain, etc.) are to be evaluated by a baseline echocardiogram with or without stress test as needed in addition to electrocardiogram (EKG) to rule out QTc prolongation
  * Patients with underlying cardiopulmonary dysfunction are excluded from the study

Inclusion Criteria for Registration (Step 1):

* Meeting the eligibility criteria for pre-registration (Step 0)
* The melanoma must harbor a c-KIT mutation determined by PCR and sequencing as defined in the protocol either by local assessment or Massachusetts General Hospital (MGH)
* Measurable disease, defined as at least one measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
* At least 4 weeks since prior chemotherapy, radiotherapy or immunotherapy and the beginning of protocol therapy and the patient must have recovered from toxicity due to the previous therapy
* History or clinical evidence of brain metastasis allowed provided the following criteria are met:

  * Completed radiotherapy or surgical treatment of brain lesions and there is no evidence of central nervous system (CNS) progression for ≥ 8 weeks
  * Must not require corticosteroids for treatment of cerebral edema from brain metastases
* Negative pregnancy test
* Fertile patients must use effective contraception
* Patients must have the following within 4 weeks of registration:

  * computed tomography (CT) chest with intravenous (IV) and oral agent
  * CT pelvis/abdomen with IV and oral agent
  * MRI brain with gadolinium
* Baseline bone scan required for patients with known bone metastases, elevated alkaline phosphatase, or symptoms raising suspicion of bone metastases
* White blood count (WBC) ≥ 3,000/mm³
* Absolute granulocyte count (AGC) ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Creatinine ≤ 2.0 times upper limit of normal (ULN) OR creatinine clearance (CrCl) ≥ 40 mL/min
* Total bilirubin ≤ 1.5 times ULN (\< 3.0 times ULN in the presence of Gilbert disease)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN (≤ 5.0 times ULN in the presence of liver metastases)
* Serum potassium and magnesium normal (repletion allowed)
* Total serum calcium or ionized calcium ≥ institutional lower limit of normal
* International normalized ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) wtihin normal limits

  * Therapeutic anticoagulation with warfarin allowed provided INR ≤ 1.5 or PTT normal prior to initiating anticoagulation therapy

Exclusion Criteria for Registration (Step 1):

* Pregnant or nursing
* Concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (i.e., phenytoin, carbamazepine, or phenobarbital), rifampin, or Hypericum perforatum (St. John wort)
* Uncontrolled hypertension, defined as systolic blood pressure ≥ 150 mm Hg or diastolic blood pressure ≥ 90 mm Hg

  * Hypertension that is adequately controlled with medication allowed
* QTc prolongation, defined as a QTc interval ≥ 450 msecs
* Serious intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics

Primary outcomes:
measure: Objective Response Rate Among KIT-positive Patients
timeFrame: Every 6 weeks; up to 5 years
Secondary outcomes:
measure: Duration of Response for Dasatinib Monotherapy in This Patient Population
timeFrame: Every 6 weeks; up to 5 years
measure: Progression-free Survival
timeFrame: Every 6 weeks; up to 5 years
Other outcomes:
measure: To Evaluate the PDGFR Expression, and Activation of Src Family Kinases in Tumor Samples and Correlate These Parameters With Response to Treatment.
timeFrame: Every 6 weeks; up to 5 years
Locations:
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
state: Arkansas
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Fort Lauderdale
country: United States
facility: Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
state: Florida
city: Jacksonville
country: United States
facility: Baptist Cancer Institute - Jacksonville
state: Florida
city: Jupiter
country: United States
facility: Ella Milbank Foshay Cancer Center at Jupiter Medical Center
state: Florida
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute at Florida Hospital Orlando
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: 'Aiea
country: United States
facility: Kapiolani Medical Center at Pali Momi
state: Hawaii
city: 'Aiea
country: United States
facility: Oncare Hawaii, Incorporated - Pali Momi
state: Hawaii
city: Honolulu
country: United States
facility: Cancer Research Center of Hawaii
state: Hawaii
city: Honolulu
country: United States
facility: OnCare Hawaii, Incorporated - Lusitana
state: Hawaii
city: Honolulu
country: United States
facility: Queen's Cancer Institute at Queen's Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: Straub Clinic and Hospital, Incorporated
state: Hawaii
city: Honolulu
country: United States
facility: Kuakini Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: OnCare Hawaii, Incorporated - Kuakini
state: Hawaii
city: Honolulu
country: United States
facility: Kapiolani Medical Center for Women and Children
state: Hawaii
city: Kailua
country: United States
facility: Castle Medical Center
state: Hawaii
city: Lihue
country: United States
facility: Kauai Medical Clinic
state: Hawaii
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Elmhurst
country: United States
facility: Elmhurst Memorial Hospital
state: Illinois
city: Maywood
country: United States
facility: Cardinal Bernardin Cancer Center at Loyola University Medical Center
state: Illinois
city: Moline
country: United States
facility: Trinity Cancer Center at Trinity Medical Center - 7th Street Campus
state: Illinois
city: Moline
country: United States
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Veterans Affairs Medical Center - Indianapolis
state: Indiana
city: Indianapolis
country: United States
facility: William N. Wishard Memorial Hospital
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic, PC
state: Iowa
city: Bettendorf
country: United States
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, LLP
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center - Sioux City
state: Iowa
city: Sioux City
country: United States
facility: St. Luke's Regional Medical Center
state: Iowa
city: Chanute
country: United States
facility: Cancer Center of Kansas, PA - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas, PA - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas, PA - El Dorado
state: Kansas
city: Fort Scott
country: United States
facility: Cancer Center of Kansas - Fort Scott
state: Kansas
city: Independence
country: United States
facility: Cancer Center of Kansas-Independence
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas, PA - Kingman
state: Kansas
city: Lawrence
country: United States
facility: Lawrence Memorial Hospital
state: Kansas
city: Liberal
country: United States
facility: Cancer Center of Kansas, PA - Liberal
state: Kansas
city: McPherson
country: United States
facility: Cancer Center of Kansas, PA - McPherson
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas, PA - Newton
state: Kansas
city: Overland Park
country: United States
facility: Menorah Medical Center
state: Kansas
city: Overland Park
country: United States
facility: Saint Luke's Hospital - South
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas, PA - Parsons
state: Kansas
city: Prairie Village
country: United States
facility: CCOP - Kansas City
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas, PA - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas, PA - Salina
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas, PA - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates in Womens Health, PA - North Review
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas, PA - Winfield
state: Kansas
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Escanaba
country: United States
facility: Green Bay Oncology, Limited - Escanaba
state: Michigan
city: Iron Mountain
country: United States
facility: Dickinson County Healthcare System
state: Michigan
city: Kalamazoo
country: United States
facility: Borgess Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy and Unity Cancer Center at Mercy Hospital
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Mercy and Unity Cancer Center at Unity Hospital
state: Minnesota
city: Hutchinson
country: United States
facility: Hutchinson Area Health Care
state: Minnesota
city: Maplewood
country: United States
facility: HealthEast Cancer Care at St. John's Hospital
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology - Maplewood
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center - Minneapolis
state: Minnesota
city: New Ulm
country: United States
facility: New Ulm Medical Center
state: Minnesota
city: Robbinsdale
country: United States
facility: Humphrey Cancer Center at North Memorial Outpatient Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Saint Louis Park
country: United States
facility: Park Nicollet Cancer Center
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital Cancer Care Center
state: Minnesota
city: Saint Paul
country: United States
facility: United Hospital
state: Minnesota
city: Shakopee
country: United States
facility: St. Francis Cancer Center at St. Francis Medical Center
state: Minnesota
city: Stillwater
country: United States
facility: Lakeview Hospital
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Willmar
country: United States
facility: Willmar Cancer Center at Rice Memorial Hospital
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Oncology - Woodbury
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute at Saint Luke's Hospital
state: Missouri
city: Kansas City
country: United States
facility: North Kansas City Hospital
state: Missouri
city: Kansas City
country: United States
facility: Heartland Hematology Oncology Associates, Incorporated
state: Missouri
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Lee's Summit
country: United States
facility: Saint Luke's East - Lee's Summit
state: Missouri
city: Liberty
country: United States
facility: Parvin Radiation Oncology
state: Missouri
city: Saint Joseph
country: United States
facility: Heartland Regional Medical Center
state: Missouri
city: Saint Joseph
country: United States
facility: Saint Joseph Oncology, Incorporated
state: Missouri
city: Springfield
country: United States
facility: CCOP - Cancer Research for the Ozarks
state: Missouri
city: Springfield
country: United States
facility: St. John's Regional Health Center
state: Missouri
city: Springfield
country: United States
facility: Hulston Cancer Center at Cox Medical Center South
state: Missouri
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Billings
country: United States
facility: St. Vincent Healthcare Cancer Care Services
state: Montana
city: Billings
country: United States
facility: Hematology-Oncology Centers of the Northern Rockies - Billings
state: Montana
city: Billings
country: United States
facility: Billings Clinic - Downtown
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Cancer Center
state: Montana
city: Butte
country: United States
facility: St. James Healthcare Cancer Care
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic - Main Facility
state: Montana
city: Great Falls
country: United States
facility: Sletten Cancer Institute at Benefis Healthcare
state: Montana
city: Helena
country: United States
facility: St. Peter's Hospital
state: Montana
city: Kalispell
country: United States
facility: Glacier Oncology, PLLC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Medical Oncology at KRMC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Specialists at Montana Cancer Center
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
state: Montana
city: Bismarck
country: United States
facility: Medcenter One Hospital Cancer Care Center
state: North Dakota
city: Bismarck
country: United States
facility: Mid Dakota Clinic, PC
state: North Dakota
city: Bismarck
country: United States
facility: St. Alexius Medical Center Cancer Center
state: North Dakota
city: Akron
country: United States
facility: Summa Center for Cancer Care at Akron City Hospital
state: Ohio
city: Barberton
country: United States
facility: Barberton Citizens Hospital
state: Ohio
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Cancer Care Center at MetroHealth Medical Center
state: Ohio
city: Lima
country: United States
facility: St. Rita's Medical Center
state: Ohio
city: Tulsa
country: United States
facility: Natalie Warren Bryant Cancer Center at St. Francis Hospital
state: Oklahoma
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Lewistown
country: United States
facility: Lewistown Hospital
state: Pennsylvania
city: Paoli
country: United States
facility: Cancer Center of Paoli Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Centers
state: Pennsylvania
city: State College
country: United States
facility: Mount Nittany Medical Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: CCOP - Main Line Health
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Cancer Center at Lankenau Hospital
state: Pennsylvania
city: Chippewa Falls
country: United States
facility: Marshfield Clinic - Chippewa Center
state: Wisconsin
city: Eau Claire
country: United States
facility: Marshfield Clinic Cancer Care at Regional Cancer Center
state: Wisconsin
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Mary's Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: St. Mary's Hospital Medical Center - Green Bay
state: Wisconsin
city: Green Bay
country: United States
facility: St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Johnson Creek
country: United States
facility: UW Cancer Center Johnson Creek
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
state: Wisconsin
city: Manitowoc
country: United States
facility: Holy Family Memorial Medical Center Cancer Care Center
state: Wisconsin
city: Marinette
country: United States
facility: Bay Area Cancer Care Center at Bay Area Medical Center
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic - Marshfield Center
state: Wisconsin
city: Minocqua
country: United States
facility: Marshfield Clinic - Lakeland Center
state: Wisconsin
city: Mukwonago
country: United States
facility: D.N. Greenwald Center
state: Wisconsin
city: Oconomowoc
country: United States
facility: Regional Cancer Center at Oconomowoc Memorial Hospital
state: Wisconsin
city: Oconto Falls
country: United States
facility: Green Bay Oncology, Limited - Oconto Falls
state: Wisconsin
city: Rhinelander
country: United States
facility: Ministry Medical Group at Saint Mary's Hospital
state: Wisconsin
city: Rice Lake
country: United States
facility: Marshfield Clinic - Indianhead Center
state: Wisconsin
city: Sheboygan
country: United States
facility: St. Nicholas Hospital
state: Wisconsin
city: Stevens Point
country: United States
facility: Marshfield Clinic at Saint Michael's Hospital
state: Wisconsin
city: Sturgeon Bay
country: United States
facility: Green Bay Oncology, Limited - Sturgeon Bay
state: Wisconsin
city: Waukesha
country: United States
facility: Waukesha Memorial Hospital Regional Cancer Center
state: Wisconsin
city: Wausau
country: United States
facility: Marshfield Clinic - Wausau Center
state: Wisconsin
city: Weston
country: United States
facility: Marshfield Clinic - Weston Center
state: Wisconsin
city: Wisconsin Rapids
country: United States
facility: Marshfield Clinic - Wisconsin Rapids Center
state: Wisconsin
city: Casper
country: United States
facility: Rocky Mountain Oncology
state: Wyoming
Study officials:
affiliation: Massachusetts General Hospital
name: Donald P. Lawrence, MD
role: STUDY_CHAIR
affiliation: Tufts Medical Center Cancer Center
name: Kevin Kalinsky, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kalinsky K, Lee S, Rubin KM, Lawrence DP, Iafrarte AJ, Borger DR, Margolin KA, Leitao MM Jr, Tarhini AA, Koon HB, Pecora AL, Jaslowski AJ, Cohen GI, Kuzel TM, Lao CD, Kirkwood JM. A phase 2 trial of dasatinib in patients with locally advanced or stage IV mucosal, acral, or vulvovaginal melanoma: A trial of the ECOG-ACRIN Cancer Research Group (E2607). Cancer. 2017 Jul 15;123(14):2688-2697. doi: 10.1002/cncr.30663. Epub 2017 Mar 23.
citation: Kalinsky K, Hong F, McCourt CK, Sachdev JC, Mitchell EP, Zwiebel JA, Doyle LA, McShane LM, Li S, Gray RJ, Rubinstein LV, Patton D, Williams PM, Hamilton SR, Conley BA, O'Dwyer PJ, Harris LN, Arteaga CL, Chen AP, Flaherty KT. Effect of Capivasertib in Patients With an AKT1 E17K-Mutated Tumor: NCI-MATCH Subprotocol EAY131-Y Nonrandomized Trial. JAMA Oncol. 2021 Feb 1;7(2):271-278. doi: 10.1001/jamaoncol.2020.6741.