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

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ClinicalTrials.gov Identifier: NCT01514864
Recruitment Status : Terminated (Lack of efficacy and slow accrual)
First Posted : January 23, 2012
Results First Posted : December 3, 2015
Last Update Posted : December 3, 2015
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Carcinoma, Non-small Cell Lung
Intervention Drug: Dasatinib
Enrollment 19

Recruitment Details  
Pre-assignment Details A total of 19 patients were enrolled, and 14 received treatment in 2 cohorts: 9 with nonsmall-cell lung cancer (NSCLC) and an inactivating B-RAF mutation and 5 with NSCLC and a discoidin domain receptor 2 (DDR2) mutation.
Arm/Group Title Dasatinib, 140 mg (NSCLC With Inactivating B-RAF Mutation) Dasatinib, 140 mg (NSCLC With DDR2 Mutation)
Hide Arm/Group Description 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 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
Period Title: Overall Study
Started 9 5
Completed 0 [1] 0
Not Completed 9 5
Reason Not Completed
Disease progression             7             5
Study drug toxicity             2             0
[1]
Study was terminated; no patients completed study treatment
Arm/Group Title Dasatinib, 140 mg (NSCLC With Inactivating B-RAF Mutation) Dasatinib, 140 mg (NSCLC With DDR2 Mutation) Total
Hide Arm/Group Description 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 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 Total of all reporting groups
Overall Number of Baseline Participants 9 5 14
Hide Baseline Analysis Population Description
All participants who received at least 1 dose of study drug
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 5 participants 14 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
3
  33.3%
3
  60.0%
6
  42.9%
>=65 years
6
  66.7%
2
  40.0%
8
  57.1%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 9 participants 5 participants 14 participants
67.0
(51.0 to 75.0)
63.0
(50.0 to 73.0)
66.5
(50.0 to 75.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 5 participants 14 participants
Female
5
  55.6%
1
  20.0%
6
  42.9%
Male
4
  44.4%
4
  80.0%
8
  57.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 5 participants 14 participants
American Indian or Alaska Native
1
  11.1%
0
   0.0%
1
   7.1%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
1
  20.0%
1
   7.1%
White
8
  88.9%
4
  80.0%
12
  85.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 9 participants 5 participants 14 participants
Hispanic/Latino 1 0 1
Not Hispanic/Latino 5 5 10
Not reported 3 0 3
Time from cancer diagnosis to start of study therapy  
Median (Full Range)
Unit of measure:  Months
Number Analyzed 9 participants 5 participants 14 participants
14.4
(6.2 to 21.7)
8.5
(1.5 to 51.6)
12.1
(1.5 to 51.6)
Tumor Type  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 9 participants 5 participants 14 participants
Nonsmall-cell lung carcinoma 9 5 14
Other 0 0 0
Nonsmall-cell lung carcinoma histology  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 9 participants 5 participants 14 participants
Adenocarcinoma 7 1 8
Bronco-alveolar carcinoma 1 0 1
Large cell carcinoma 1 0 1
Squamous cell carcinoma 0 4 4
Histopathologic Grade  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 9 participants 5 participants 14 participants
G2-moderately differentiated 2 2 4
G3-poorly differentiated 2 0 2
GX-grade cannot be assessed 5 3 8
Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 9 participants 5 participants 14 participants
ECOG score 0 1 1 2
ECOG score 1 6 3 9
ECOG score 2 2 1 3
[1]
Measure Description: ECOG is a 6-item scale used to assess disease progression, daily functioning, and appropriate treatment and prognosis. Performance status is scored on a scale ranging from 0-5, with (best score) 0=fully active and able to carry on all predisease performance without restriction and (worst score) 5=death.
Number of Index Lesions  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 9 participants 5 participants 14 participants
1 2 1 3
2 0 2 2
3 4 1 5
4 3 1 4
1.Primary Outcome
Title Objective Response Rate (ORR)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug. Because no patients had a response of CR or PR, ORR could not be calculated.
Arm/Group Title Dasatinib, 140 mg (NSCLC With Inactivating B-RAF Mutation) Dasatinib, 140 mg (NSCLC With DDR2 Mutation)
Hide Arm/Group Description:
Participants with nonsmall-cell lung cancer (NSCLC) with inactivating B-RAF mutation received dasatinib, 140 mg, once daily as a tablet until unacceptable toxicity or disease progression occurred
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
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
2.Secondary Outcome
Title Duration of Response (DOR)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug. Because no patients had a response of CR or PR, DOR could not be calculated.
Arm/Group Title Dasatinib, 140 mg (NSCLC With Inactivating B-RAF Mutation) Dasatinib, 140 mg (NSCLC With DDR2 Mutation)
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Overall Survival
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received treatment
Arm/Group Title Dasatinib, 140 mg (NSCLC With Inactivating B-RAF Mutation) Dasatinib, 140 mg (NSCLC With DDR2 Mutation)
Hide Arm/Group Description:
Participants with nonsmall-cell lung cancer (NSCLC) with inactivating B-RAF mutation received dasatinib, 140 mg, once daily as a tablet until unacceptable toxicity or disease progression occurred
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
Overall Number of Participants Analyzed 9 5
Median (90% Confidence Interval)
Unit of Measure: Months
3.06
(0.76 to 6.47)
4.21 [1] 
(0.82 to NA)
[1]
The upper limit Confidence Interval cannot be estimated
4.Secondary Outcome
Title Progression-free Survival (PFS) Distribution
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug
Arm/Group Title Dasatinib, 140 mg (NSCLC With Inactivating B-RAF Mutation) Dasatinib, 140 mg (NSCLC With DDR2 Mutation)
Hide Arm/Group Description:
Participants with nonsmall-cell lung cancer (NSCLC) with inactivating B-RAF mutation received dasatinib, 140 mg, once daily as a tablet until unacceptable toxicity or disease progression occurred
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
Overall Number of Participants Analyzed 9 5
Median (90% Confidence Interval)
Unit of Measure: Percentage of participants
1.41
(0.72 to 1.87)
1.38
(0.59 to 2.96)
5.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug
Arm/Group Title Dasatinib, 140 mg (NSCLC With Inactivating B-RAF Mutation) Dasatinib, 140 mg (NSCLC With DDR2 Mutation)
Hide Arm/Group Description:
Participants with nonsmall-cell lung cancer (NSCLC) with inactivating B-RAF mutation received dasatinib, 140 mg, once daily as a tablet until unacceptable toxicity or disease progression occurred
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
Overall Number of Participants Analyzed 9 5
Median (90% Confidence Interval)
Unit of Measure: Months
1.41
(0.72 to 1.87)
1.38
(0.59 to 2.96)
6.Secondary Outcome
Title 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
Hide Description 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.
Time Frame From enrollment of last patient to 24 months or until all patients have died, whichever occurs first
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug
Arm/Group Title Dasatinib, 140 mg (NSCLC With Inactivating B-RAF Mutation) Dasatinib, 140 mg (NSCLC With DDR2 Mutation)
Hide Arm/Group Description:
Participants with nonsmall-cell lung cancer (NSCLC) with inactivating B-RAF mutation received dasatinib, 140 mg, once daily as a tablet until unacceptable toxicity or disease progression occurred
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
Overall Number of Participants Analyzed 9 5
Measure Type: Number
Unit of Measure: Participants
Death 8 4
Death within 30 days of last treatment 3 1
SAEs 7 4
Drug-related SAEs 0 1
AEs leading to discontinuation 7 2
Drug-related AEs leading to discontinuation 2 0
Drug-related AEs 6 3
7.Secondary Outcome
Title Number of Participants With Laboratory Testing Results That Meet the Criteria for Grade 3 or 4 Abnormality
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received study drug.
Arm/Group Title Dasatinib, 140 mg
Hide Arm/Group Description:
Participants with nonsmall-cell lung cancer (NSCLC) received dasatinib, 140 mg, once daily as a tablet until unacceptable toxicity or disease progression occurred. Data from both arms were combined for safety reporting, because the safety profile of dasatinib should not have be affected by the type of mutation in the tumor. In addition, pooling the data from both arms increased the robustness of the data set.
Overall Number of Participants Analyzed 14
Measure Type: Number
Unit of Measure: Participants
Hemoglobin, Grade 3 2
Alkaline phosphatase, Grade 3 1
Total bilirubin, Grade 3 1
Calcium, low, Grade 3 1
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Dasatinib, 140 mg
Hide Arm/Group Description Participants with nonsmall-cell lung cancer received dasatinib, 140 mg, once daily as a tablet until unacceptable toxicity or disease progression occurred. Data from both arms were combined for safety reporting, because the safety profile of dasatinib should not have be affected by the type of mutation in the tumor. In addition, pooling the data from both arms increased the robustness of the data set.
All-Cause Mortality
Dasatinib, 140 mg
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Dasatinib, 140 mg
Affected / at Risk (%)
Total   11/14 (78.57%) 
Cardiac disorders   
Angina pectoris  1  1/14 (7.14%) 
Atrial fibrillation  1  1/14 (7.14%) 
Angina unstable  1  1/14 (7.14%) 
Gastrointestinal disorders   
Diverticular perforation  1  1/14 (7.14%) 
Gastrointestinal haemorrhage  1  1/14 (7.14%) 
General disorders   
General physical health deterioration  1  1/14 (7.14%) 
Pain  1  1/14 (7.14%) 
Hepatobiliary disorders   
Cholangitis  1  1/14 (7.14%) 
Hyperbilirubinaemia  1  1/14 (7.14%) 
Infections and infestations   
Lung infection  1  2/14 (14.29%) 
Lower respiratory tract infection  1  1/14 (7.14%) 
Investigations   
Haemoglobin decreased  1  1/14 (7.14%) 
Lipase increased  1  1/14 (7.14%) 
Metabolism and nutrition disorders   
Hypercalcaemia  1  1/14 (7.14%) 
Musculoskeletal and connective tissue disorders   
Groin pain  1  1/14 (7.14%) 
Musculoskeletal chest pain  1  1/14 (7.14%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Non-small cell lung cancer  1  1/14 (7.14%) 
Neoplasm malignant  1  1/14 (7.14%) 
Malignant neoplasm progression  1  4/14 (28.57%) 
Psychiatric disorders   
Panic reaction  1  1/14 (7.14%) 
Respiratory, thoracic and mediastinal disorders   
Pleural effusion  1  2/14 (14.29%) 
Dyspnoea  1  2/14 (14.29%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Dasatinib, 140 mg
Affected / at Risk (%)
Total   13/14 (92.86%) 
Blood and lymphatic system disorders   
Thrombocytopenia  1  1/14 (7.14%) 
Cardiac disorders   
Angina pectoris  1  1/14 (7.14%) 
Ear and labyrinth disorders   
Hearing impaired  1  1/14 (7.14%) 
Eye disorders   
Uveitis  1  1/14 (7.14%) 
Eyelid oedema  1  1/14 (7.14%) 
Vision blurred  1  1/14 (7.14%) 
Eye disorder  1  1/14 (7.14%) 
Gastrointestinal disorders   
Diverticular perforation  1  1/14 (7.14%) 
Pancreatitis  1  1/14 (7.14%) 
Vomiting  1  2/14 (14.29%) 
Nausea  1  5/14 (35.71%) 
Abdominal pain upper  1  1/14 (7.14%) 
Constipation  1  1/14 (7.14%) 
Dyspepsia  1  1/14 (7.14%) 
Stomatitis  1  1/14 (7.14%) 
Diarrhoea  1  3/14 (21.43%) 
Dysphagia  1  1/14 (7.14%) 
General disorders   
Pyrexia  1  2/14 (14.29%) 
Fatigue  1  7/14 (50.00%) 
Asthenia  1  1/14 (7.14%) 
Oedema peripheral  1  3/14 (21.43%) 
Oedema  1  2/14 (14.29%) 
Extravasation  1  1/14 (7.14%) 
Chest pain  1  2/14 (14.29%) 
Pain  1  2/14 (14.29%) 
Chills  1  1/14 (7.14%) 
Hepatobiliary disorders   
Hepatic pain  1  1/14 (7.14%) 
Infections and infestations   
Lower respiratory tract infection  1  1/14 (7.14%) 
Pneumonia  1  1/14 (7.14%) 
Viral infection  1  1/14 (7.14%) 
Investigations   
Blood alkaline phosphatase increased  1  1/14 (7.14%) 
Calcium ionised increased  1  1/14 (7.14%) 
Blood alkaline phosphatase  1  1/14 (7.14%) 
Blood glucose increased  1  1/14 (7.14%) 
Blood albumin decreased  1  1/14 (7.14%) 
Haemoglobin decreased  1  2/14 (14.29%) 
Lipase increased  1  1/14 (7.14%) 
Electrocardiogram ST segment elevation  1  1/14 (7.14%) 
Weight decreased  1  1/14 (7.14%) 
Metabolism and nutrition disorders   
Decreased appetite  1  3/14 (21.43%) 
Hypoalbuminaemia  1  1/14 (7.14%) 
Hypomagnesaemia  1  1/14 (7.14%) 
Musculoskeletal and connective tissue disorders   
Groin pain  1  1/14 (7.14%) 
Muscular weakness  1  1/14 (7.14%) 
Pain in jaw  1  1/14 (7.14%) 
Nervous system disorders   
Sedation  1  1/14 (7.14%) 
Dizziness  1  1/14 (7.14%) 
Dysgeusia  1  1/14 (7.14%) 
Headache  1  3/14 (21.43%) 
Parosmia  1  1/14 (7.14%) 
Tremor  1  1/14 (7.14%) 
Neuropathy peripheral  1  2/14 (14.29%) 
Psychiatric disorders   
Anxiety  1  2/14 (14.29%) 
Confusional state  1  2/14 (14.29%) 
Insomnia  1  1/14 (7.14%) 
Renal and urinary disorders   
Nocturia  1  1/14 (7.14%) 
Urinary straining  1  1/14 (7.14%) 
Respiratory, thoracic and mediastinal disorders   
Haemoptysis  1  2/14 (14.29%) 
Pleural effusion  1  4/14 (28.57%) 
Nasal ulcer  1  1/14 (7.14%) 
Productive cough  1  1/14 (7.14%) 
Cough  1  4/14 (28.57%) 
Dyspnoea exertional  1  1/14 (7.14%) 
Wheezing  1  1/14 (7.14%) 
Dyspnoea  1  6/14 (42.86%) 
Skin and subcutaneous tissue disorders   
Dry skin  1  1/14 (7.14%) 
Night sweats  1  1/14 (7.14%) 
Pruritus  1  1/14 (7.14%) 
Vascular disorders   
Deep vein thrombosis  1  1/14 (7.14%) 
Vasculitis  1  1/14 (7.14%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
The study was terminated due to lack of efficacy and slow enrollment of patients.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01514864     History of Changes
Other Study ID Numbers: CA180-385
2011-003128-11 ( EudraCT Number )
First Submitted: January 18, 2012
First Posted: January 23, 2012
Results First Submitted: July 23, 2015
Results First Posted: December 3, 2015
Last Update Posted: December 3, 2015