Dasatinib in Treating Patients With Locally Advanced or Metastatic Mucosal Melanoma, Acral Melanoma, or Vulvovaginal Melanoma That Cannot Be Removed By Surgery

Melanoma (Skin) Clinical Trial

Official title:

A Phase II Trial of Dasatinib in KIT-Positive Patients With Unresectable Locally Advanced or Stage IV Mucosal, Acral and Vulvovaginal Melanomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00700882
• Other study ID #: E2607
• Secondary ID: E2607U10CA180794
• Status: Completed
• Phase: Phase 2
• Start date: July 2, 2009
• Est. completion date: December 28, 2020

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: December 28, 2020
• Est. primary completion date: May 6, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

Drug:
• dasatinib
Patients receive oral dasatinib at 70 mg twice daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Locations

Country	Name	City	State
United States	Kapiolani Medical Center at Pali Momi	'Aiea	Hawaii
United States	Oncare Hawaii, Incorporated - Pali Momi	'Aiea	Hawaii
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	McFarland Clinic, PC	Ames	Iowa
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Greater Baltimore Medical Center Cancer Center	Baltimore	Maryland
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Barberton Citizens Hospital	Barberton	Ohio
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota
United States	Mid Dakota Clinic, PC	Bismarck	North Dakota
United States	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Marshfield Clinic - Chippewa Center	Chippewa Falls	Wisconsin
United States	Case Comprehensive Cancer Center	Cleveland	Ohio
United States	MetroHealth Cancer Care Center at MetroHealth Medical Center	Cleveland	Ohio
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	Marshfield Clinic Cancer Care at Regional Cancer Center	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Elmhurst Memorial Hospital	Elmhurst	Illinois
United States	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan
United States	Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	St. Peter's Hospital	Helena	Montana
United States	Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Kuakini Medical Center	Honolulu	Hawaii
United States	OnCare Hawaii, Incorporated - Kuakini	Honolulu	Hawaii
United States	OnCare Hawaii, Incorporated - Lusitana	Honolulu	Hawaii
United States	Queen's Cancer Institute at Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital, Incorporated	Honolulu	Hawaii
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Veterans Affairs Medical Center - Indianapolis	Indianapolis	Indiana
United States	William N. Wishard Memorial Hospital	Indianapolis	Indiana
United States	Dickinson County Healthcare System	Iron Mountain	Michigan
United States	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida
United States	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin
United States	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida
United States	Castle Medical Center	Kailua	Hawaii
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology at KRMC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Heartland Hematology Oncology Associates, Incorporated	Kansas City	Missouri
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Cancer Institute at Saint Luke's Hospital	Kansas City	Missouri
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas
United States	Parvin Radiation Oncology	Liberty	Missouri
United States	Kauai Medical Clinic	Lihue	Hawaii
United States	St. Rita's Medical Center	Lima	Ohio
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin
United States	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	Minnesota Oncology - Maplewood	Maplewood	Minnesota
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Cancer Center of Kansas, PA - McPherson	McPherson	Kansas
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Marshfield Clinic - Lakeland Center	Minocqua	Wisconsin
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois
United States	D.N. Greenwald Center	Mukwonago	Wisconsin
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Regional Cancer Center at Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin
United States	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's Hospital - South	Overland Park	Kansas
United States	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	UPMC Cancer Centers	Pittsburgh	Pennsylvania
United States	CCOP - Kansas City	Prairie Village	Kansas
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Ministry Medical Group at Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Clinic - Indianhead Center	Rice Lake	Wisconsin
United States	Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Saint Joseph Oncology, Incorporated	Saint Joseph	Missouri
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	Regions Hospital Cancer Care Center	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	St. Nicholas Hospital	Sheboygan	Wisconsin
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	St. John's Regional Health Center	Springfield	Missouri
United States	Stanford Cancer Center	Stanford	California
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	Marshfield Clinic at Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Waukesha Memorial Hospital Regional Cancer Center	Waukesha	Wisconsin
United States	Marshfield Clinic - Wausau Center	Wausau	Wisconsin
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Marshfield Clinic - Weston Center	Weston	Wisconsin
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology - Woodbury	Woodbury	Minnesota
United States	CCOP - Main Line Health	Wynnewood	Pennsylvania
United States	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To Evaluate the PDGFR Expression, and Activation of Src Family Kinases in Tumor Samples and Correlate These Parameters With Response to Treatment.	Objective response is defined as complete response (CR) or partial response (PR) per Solid Tumor Response Criteria (RECIST). Complete response is defined as disappearance of all target and non-target lesions. Partial response is defined as at least 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter.	Every 6 weeks; up to 5 years
Primary	Objective Response Rate Among KIT-positive Patients	Objective response is defined as complete response (CR) or partial response (PR) per Solid Tumor Response Criteria (RECIST). Complete response is defined as disappearance of all target and non-target lesions. Partial response is defined as at least 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter.	Every 6 weeks; up to 5 years
Secondary	Duration of Response for Dasatinib Monotherapy in This Patient Population	Duration of response is defined as the period measured from the time that measurement criteria are met for complete or partial response (whichever status is recorded first) until the first date that progressive disease is objectively documented, taking as reference the smallest measurements recorded since treatment started. Progressive disease is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s).	Every 6 weeks; up to 5 years
Secondary	Progression-free Survival	Progression-free survival is defined as the time from registration to development of progressive disease. Patients without documented progressive disease are censored at the date of last disease assessment. Progressive disease is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s).	Every 6 weeks; up to 5 years