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

Carcinoma, Non-small Cell Lung Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01514864
• Other study ID #: CA180-385
• Secondary ID: 2011-003128-11
• Status: Terminated
• Phase: Phase 2
• Start date: May 31, 2012
• Est. completion date: July 23, 2014

Study information

• Verified date: December 2023
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 19
• Est. completion date: July 23, 2014
• Est. primary completion date: July 23, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-small Cell Lung
• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Dasatinib
Tablet, oral, 140 mg, once daily until unacceptable toxicity or disease progression

Locations

Country	Name	City	State
Brazil	Local Institution	Barretos	Sao Paulo
Brazil	Local Institution	Barretos	Sao Paulo
Brazil	Local Institution	S?o Paulo	Sao Paulo
Brazil	Local Institution	Sao Paulo
Canada	The Ottawa Hospital Cancer Centre	Ottawa	Ontario
Germany	Local Institution	Frankfurt
Germany	Local Institution	Heidelberg
Germany	Local Institution	Heidelberg
Germany	Local Institution	Koeln
Germany	Local Institution	Koeln
Poland	Local Institution	Gdansk
Poland	Local Institution	Lodz
Poland	Local Institution	Warsaw
Taiwan	Local Institution	Taipei
United Kingdom	Local Institution	Cambridge	Cambridgeshire
United Kingdom	Local Institution	Cambridge
United Kingdom	Local Institution	Edinburgh	Midlothian
United Kingdom	Local Institution	Gwent
United Kingdom	Local Institution	London	Greater London
United Kingdom	Local Institution	Manchester	Greater Manchester
United Kingdom	Local Institution	Sutton	Surrey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering Nassau	New York	New York
United States	H. Lee Moffitt Cancer & Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  Germany,  Poland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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