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

This study has been terminated.
(Lack of efficacy and slow accrual)
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01514864
First received: January 18, 2012
Last updated: November 2, 2015
Last verified: November 2015
  Purpose
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.

Condition Intervention Phase
Carcinoma, Non-small Cell Lung
Drug: Dasatinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Dasatinib in Subjects With Advanced Cancers Harboring DDR2 Mutation or Inactivating B-RAF Mutation

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Objective Response Rate (ORR) [ Time Frame: From enrollment of last patient to 24 months or until all patients have died, whichever occurs first ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Duration of Response (DOR) [ Time Frame: From enrollment of last patient to 24 months or until all patients have died, whichever occurs first ] [ Designated as safety issue: No ]
    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.

  • Overall Survival [ Time Frame: From enrollment of last patient to 24 months or until all patients have died, whichever occurs first ] [ Designated as safety issue: No ]
    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.

  • Progression-free Survival (PFS) Distribution [ Time Frame: From Day 1 of study treatment to Week 12 ] [ Designated as safety issue: No ]
    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

  • Progression-free Survival (PFS) [ Time Frame: From Day 1 of study treatment to Week 12 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: From enrollment of last patient to 24 months or until all patients have died, whichever occurs first ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Laboratory Testing Results That Meet the Criteria for Grade 3 or 4 Abnormality [ Time Frame: From enrollment of last patient to 24 months or until all patients have died, whichever occurs first ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 19
Study Start Date: May 2012
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dasatinib, 140 mg (NSCLC With Inactivating B-RAF Mutation)
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
Tablet, oral, 140 mg, once daily until unacceptable toxicity or disease progression
Experimental: Dasatinib, 140 mg (NSCLC With DDR2 Mutation)
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
Tablet, oral, 140 mg, once daily until unacceptable toxicity or disease progression

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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:

    • NSCLC with inactivating B-RAF mutation
    • NSCLC with discoidin domain receptor 2 (DDR2) mutation
    • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01514864

Locations
United States, Florida
H. Lee Moffitt Cancer & Research Institute
Tampa, Florida, United States, 33612
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Brazil
Local Institution
Barretos, Sao Paulo, Brazil, 14784
Local Institution
S?o Paulo, Sao Paulo, Brazil, 05403
Canada, Ontario
The Ottawa Hospital Cancer Centre
Ottawa, Ontario, Canada, K1H 8L6
Germany
Local Institution
Frankfurt, Germany, 60488
Local Institution
Heidelberg, Germany, 69120
Local Institution
Heidelberg, Germany, 69126
Local Institution
Koeln, Germany, 50924
Local Institution
Koeln, Germany, 50931
Poland
Local Institution
Gdansk, Poland, 80-219
Local Institution
Lodz, Poland, 93-509
Local Institution
Warsaw, Poland, 02-781
Taiwan
Local Institution
Taipei, Taiwan, 112
United Kingdom
Local Institution
Cambridge, Cambridgeshire, United Kingdom, CB2 2QQ
Local Institution
London, Greater London, United Kingdom, SW3 6JJ
Local Institution
Manchester, Greater Manchester, United Kingdom, M20 4BX
Local Institution
Edinburgh, Midlothian, United Kingdom, EH4 2XU
Local Institution
Sutton, Surrey, United Kingdom, SM2 5PT
Local Institution
Gwent, United Kingdom, NP20 2UB
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01514864     History of Changes
Other Study ID Numbers: CA180-385  2011-003128-11 
Study First Received: January 18, 2012
Results First Received: July 23, 2015
Last Updated: November 2, 2015
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Germany: Federal Institute for Drugs and Medical Devices
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
Brazil: National Committee of Ethics in Research
Brazil: National Health Surveillance Agency
Canada: Health Canada
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Taiwan : Food and Drug Administration
Korea: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Dasatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 23, 2016