Trial of Dasatinib in Patients With Advanced Cancers Harboring DDR2 Mutation or Inactivating B-RAF Mutation

Study Overview
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Brief Summary
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The purpose of this study is to establish whether patients with malignancy harboring a discoidin domain receptor 2 mutation or an inactivating B-RAF mutation will respond to dasatinib.

Official Title
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Phase II Trial of Dasatinib in Subjects With Advanced Cancers Harboring DDR2 Mutation or Inactivating B-RAF Mutation

Conditions
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Carcinoma, Non-small Cell Lung

Intervention / Treatment
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* Drug: Dasatinib


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria Diagnosis of advanced malignancy, nonsmall-cell lung cancer (NSCLC) only during stage 1 of accrual. Nonsynonymous mutation of B-RAF or DDR2, defined as follows:. i) NSCLC with inactivating B-RAF mutation. ii) NSCLC with discoidin domain receptor 2 (DDR2) mutation. iii) Malignancy of other histology with DDR2 mutation or inactivating B-RAF mutation, or NSCLC having a B-RAF mutation that is not functionally characterized. At least 1 target lesion per Response Evaluation Criteria in Solid Tumors, vol 1.1, on baseline staging evaluation. Disease progression after ≥ 1 prior treatment regimen. Exclusion Criteria Pleural or pericardial effusion, Grade >1. QTcF >470 msec (Grade ≥2) or diagnosed congenital long QT syndrome. Absolute granulocyte count <1500/mm^3. Hemoglobin level <10 g/dL. Platelet count < 75,000/mm^3. Serum calcium level <institutional lower limit of normal. Hypokalemia, hypophosphatemia, or hypomagnesemia, Grade >1, despite supplementation. Creatinine >3*institutional upper limit of normal (ULN). Total bilirubin level >1.5*ULN. Alanine transaminase level >3*ULN. Other protocol-defined Inclusion/Exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dasatinib, 140 mg (NSCLC With Inactivating B-RAF Mutation)<br>Participants with nonsmall-cell lung cancer (NSCLC) and an inactivating B-RAF mutation received dasatinib, 140 mg, once daily as a tablet until unacceptable toxicity or disease progression occurred | Drug: Dasatinib<br>* Tablet, oral, 140 mg, once daily until unacceptable toxicity or disease progression<br>|
| Experimental: Dasatinib, 140 mg (NSCLC With DDR2 Mutation)<br>Participants with NSCLC and a discoidin domain receptor 2 (DDR2) mutation received dasatinib, 140 mg, once daily as a tablet until unacceptable toxicity or disease progression occurred | Drug: Dasatinib<br>* Tablet, oral, 140 mg, once daily until unacceptable toxicity or disease progression<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR is defined as the percentage of patients with best tumor response of either Partial Response (a 30% or greater decrease in the sum of the longest diameter [LD] of all lesions in reference to the baseline sum LD) or Complete Response (disappearance of clinical and radiologic evidence of target lesions), according to Response Evaluation Criteria in Solid Tumors. | From enrollment of last patient to 24 months or until all patients have died, whichever occurs first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) | DOR is defined as the time from the first assessment documentation of partial response (PR) or complete response (CR) until the first assessment documentation of disease progression. | From enrollment of last patient to 24 months or until all patients have died, whichever occurs first | 
| Overall Survival | Overall survival is defined as the time from treatment start date to the date of death. If a patient does not die, survival will be censored on the last date the patient was known to be alive. | From enrollment of last patient to 24 months or until all patients have died, whichever occurs first | 
| Progression-free Survival (PFS) Distribution | PFS distribution is defined as the percentage of patients with no documentation of disease progression at a specified time point. Confidence interval computed using the Brookmeyer and Crowley method | From Day 1 of study treatment to Week 12 | 
| Progression-free Survival (PFS) | PFS is defined as the time from treatment start date to the earliest evidence of disease progression or death. Patients who die or whose disease does not progress will be censored on the date of their last tumor assessment. | From Day 1 of study treatment to Week 12 | 
| Number of Patients With Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs) Leading to Discontinuation, and Drug-related AEs Leading to Discontinuation | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=having certain, probable, possible, or unknown relationship to study drug. | From enrollment of last patient to 24 months or until all patients have died, whichever occurs first | 
| Number of Participants With Laboratory Testing Results That Meet the Criteria for Grade 3 or 4 Abnormality | Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to adverse event. Laboratory values graded by Common Terminology Criteria for Adverse Events, volume 3. Hemoglobin, Grade 3: <8.0 - 6.5 g/dL, <4.9-4.0 mmol/L, <80-65 g/L. Alkaline phosphatase, Grade 3: >5.0-20.0*upper limit of normal (ULN). Total bilirubin, Grade 3: >3.0-10.0*ULN. Calcium, low, Grade 3: <7.0-6.0 mg/dL, <1.75-1.5 mmol/L. | From enrollment of last patient to 24 months or until all patients have died, whichever occurs first |