Phase II Trial of Dasatinib (BMS 354825) for Recurrent or Metastatic c-KIT Expressing Adenoid Cystic Carcinoma and Non-adenoid Cystic Malignant Salivary Tumors
Overview
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 55
- Locations
- 34
- Primary Endpoint
- Progression-free Survival
Overview
Brief Summary
This phase II trial is studying how well dasatinib works in treating patients with malignant salivary gland tumors that have come back after treatment or have spread to other parts of the body. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed Description
PRIMARY OBJECTIVES:
I. Determine the objective response rate (complete response plus partial response) of dasatinib in adenoid cystic carcinoma (ACC).
II. Determine the progression-free survival of dasatinib in ACC.
SECONDARY OBJECTIVES:
I. Determine the duration of response. II. Determine the stable disease rate and duration of stable disease. III. Determine progression-free survival. IV. Determine the median survival. V. Determine the overall survival. VI. Determine the safety and tolerability.
TERTIARY OBJECTIVES:
I. To examine biomarkers that relate to SRC proto-oncogene, non-receptor tyrosine kinase (Src) signal transduction and to correlate these biomarkers with clinical response to dasatinib in ACC and non-ACC malignant salivary gland tumors (MSGT).
II. Determine if activating mutations in platelet-derived growth factor alpha polypeptide (PDGFA) and KIT are associated with response in ACC.
OUTLINE:
Patients receive dasatinib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed at 8 weeks.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically or cytologically confirmed malignant salivary gland tumor (MSGT), including one of the following histologic subtypes:
- •Adenoid cystic carcinoma (ACC) with c v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (Kit) overexpression or non-ACC MSGT that is not amenable to potentially curable surgery or radiation
- •c-KIT overexpression in ACC patients is defined as cluster of differentiation (CD) 117 staining by immunohistochemistry (IHC) in 25% of tumor cells
- •No stipulation for c-KIT overexpression is not required for non-ACC MSGT patients
- •Patients must have radiographically measurable disease; radiographically measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan
- •Patients must have evidence of disease progression (objective growth of existing tumors) within 4 months of study entry
- •No known brain metastases, unless patient meets both of the following criteria:
- •Neurologic status stable for \>= 8 weeks after completion of definitive local therapy (surgery or radiotherapy)
- •No neurologic dysfunction that would confound study results
- •Life expectancy greater than 12 weeks
Exclusion Criteria
- •Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; at least 4 weeks must have elapsed since any major surgery
- •Patients may not be receiving any other investigational agents
- •No prior treatment with any other targeted agents that inhibit vascular endothelial growth factor receptor (VEGFR), Breakpoint cluster region (BCR) ABL proto-oncogene 1, non-receptor tyrosine kinase (ABL), c-Src, c-KIT, platelet-derived growth factor (PDGF) beta receptor, or ephrin type-A receptor 2 (EPHA2) (e.g., imatinib mesylate)
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to dasatinib
- •Patients with corrected QT interval (QTc) prolongation (defined as a QTc interval equal to or greater than 500 msec), serious ventricular arrhythmia (ventricular fibrillation or ventricular tachycardia greater than or equal to 3 beats in a row) or other significant echocardiogram (ECG) abnormalities are excluded
- •Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication, requirement for intravenous \[IV\] alimentation, or active peptic ulcer disease) that impairs their ability to swallow and retain dasatinib tablets are excluded
- •Patients with any of the following conditions are excluded:
- •Serious or non-healing wound, ulcer, or bone fracture
- •History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscesses within the past 28 days
- •Any history of cerebrovascular accident (CVA) or transient ischemic attack within the past 12 months
Arms & Interventions
Arm I
Patients receive dasatinib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Dasatinib (Drug)
Arm I
Patients receive dasatinib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis (Other)
Outcomes
Primary Outcomes
Progression-free Survival
Time Frame: up to 5 years
Progression-free survival from start of treatment to the time of disease progression or death from any cause was estimated using the Kaplan-Meier method.
Response Rate
Time Frame: Up to 2 months
Response rate is percentage of the best overall response which recoded from the start of the treatment until diseases progression/recurrence. Response criteria are defined using the international criteria proposed by the Response Evaluation Criteria In Solid Tumors (RECIST) Committee: Complete Response, Disappearance of all target lesions; Partial Response, \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease, neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, no occurrence of progression disease for non-target lesions, and no new lesions.
Secondary Outcomes
- Changes in Laboratory Correlates(Baseline and 4 weeks)
- Overall Survival(Up to 5 years)