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

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

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 Overview

• Status: Terminated
• Conditions: Carcinoma, Non-small Cell Lung
• Intervention / Treatment: Drug: Dasatinib

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 01246-000
    • Local Institution
  • Sao Paulo
    • Barretos, Sao Paulo, Brazil, 14784-400
      • Local Institution
    • Barretos, Sao Paulo, Brazil, 14784
      • Local Institution
    • S?o Paulo, Sao Paulo, Brazil, 05403
      • Local Institution
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital Cancer Centre
• Germany
  • Frankfurt, Germany, 60488
    • Local Institution
  • Heidelberg, Germany, 69126
    • Local Institution
  • Heidelberg, Germany, 69120
    • Local Institution
  • Koeln, Germany, 50924
    • Local Institution
  • Koeln, Germany, 50931
    • Local Institution
• Poland
  • Gdansk, Poland, 80-219
    • Local Institution
  • Lodz, Poland, 93-509
    • Local Institution
  • Warsaw, Poland, 02-781
    • Local Institution
• Taiwan
  • Taipei, Taiwan, 112
    • Local Institution
• United Kingdom
  • Cambridge, United Kingdom, CB2 2QQ
    • Local Institution
  • Gwent, United Kingdom, NP20 2UB
    • Local Institution
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 2QQ
      • Local Institution
  • Greater London
    • London, Greater London, United Kingdom, SW3 6JJ
      • Local Institution
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M20 4BX
      • Local Institution
  • Midlothian
    • Edinburgh, Midlothian, United Kingdom, EH4 2XU
      • Local Institution
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Local Institution
• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer & Research Institute
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Nassau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2012
• Primary Completion (Actual): July 23, 2014
• Study Completion (Actual): July 23, 2014

Study Registration Dates

• First Submitted: January 18, 2012
• First Submitted That Met QC Criteria: January 20, 2012
• First Posted (Estimated): January 23, 2012

Study Record Updates

• Last Update Posted (Estimated): December 19, 2023
• Last Update Submitted That Met QC Criteria: December 17, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Dasatinib
• Other Study ID Numbers: CA180-385; 2011-003128-11 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No