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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00700882
Recruitment Status : Active, not recruiting
First Posted : June 19, 2008
Results First Posted : February 24, 2020
Last Update Posted : November 17, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group

Study Description
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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.


Condition or disease Intervention/treatment Phase
Melanoma (Skin) Drug: dasatinib Phase 2

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 81 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Dasatinib in KIT-Positive Patients With Unresectable Locally Advanced or Stage IV Mucosal, Acral and Vulvovaginal Melanomas
Actual Study Start Date : May 1, 2009
Actual Primary Completion Date : May 6, 2016
Estimated Study Completion Date : December 28, 2020

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma
Drug Information available for: Dasatinib

Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.
 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.
Other Names:
  • Sprycel
  • BMS-354825


Outcome Measures
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Primary Outcome Measures :
  1. Objective Response Rate Among KIT-positive Patients [ Time Frame: Every 6 weeks; up to 5 years ]
    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.


Secondary Outcome Measures :
  1. Duration of Response for Dasatinib Monotherapy in This Patient Population [ Time Frame: Every 6 weeks; up to 5 years ]
    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).

  2. Progression-free Survival [ Time Frame: Every 6 weeks; up to 5 years ]
    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).

  3. To Evaluate the PDGFR Expression, and Activation of Src Family Kinases in Tumor Samples and Correlate These Parameters With Response to Treatment. [ Time Frame: Every 6 weeks; up to 5 years ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00700882


Locations
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Sponsors and Collaborators
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Investigators
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Study Chair: Donald P. Lawrence, MD Massachusetts General Hospital
Principal Investigator: Kevin Kalinsky, MD Tufts Medical Center Cancer Center
More Information
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Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00700882    
Other Study ID Numbers: E2607
E2607 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
U10CA180794 ( U.S. NIH Grant/Contract )
First Posted: June 19, 2008    Key Record Dates
Results First Posted: February 24, 2020
Last Update Posted: November 17, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Eastern Cooperative Oncology Group:
stage IV melanoma
acral melanoma
mucosal melanoma
vulvovaginal melanoma
stage III melanoma
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
 Nevi and Melanomas
Dasatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action