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

Phase 2TerminatedNCT01514864

Bristol-Myers Squibb19 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Carcinoma, Non-small Cell Lung

Interventions

DasatinibDRUG

Tablet, oral, 140 mg, once daily until unacceptable toxicity or disease progression

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (24)

H. Lee Moffitt Cancer & Research Institute

Tampa, Florida, United States

Outcomes

Primary Outcomes

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.

Time frame: From enrollment of last patient to 24 months or until all patients have died, whichever occurs first

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: From Day 1 of study treatment to Week 12

Data from ClinicalTrials.gov

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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.

Time frame: From enrollment of last patient to 24 months or until all patients have died, whichever occurs first