This study will determine whether the investigational drug dasatinib is effective in treatment of women with progressive advanced triple-negative breast cancer.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
55
Ucsf-Comprehensive Cancer Center
San Francisco, California, United States
Mayo Clinic Jacksonville
Jacksonville, Florida, United States
Dana-Farber Cancer Inst
Boston, Massachusetts, United States
Montefiore Medical Center
Number of Participants With Complete Response (CR) or Partial Response (PR)
Tumor response was defined as the number of participants whose best response was CR or PR, per the Response Evaluation Criteria in Solid Tumor (RECIST): CR: disappearance of all target/non-target lesions; PR: \>= 30% decrease in the sum of the LDs of target lesions relative to the baseline sum LD.
Time frame: Baseline to end of study drug therapy (up to 65 weeks).
Percentage of Participants With Complete Response (CR) or Partial Response (PR)
The percentage of participants whose best response was CR or PR, per the RECIST: CR: disappearance of all target/non-target lesions; PR: \>= 30% decrease in the sum of the LDs of target lesions relative to the baseline sum LD.
Time frame: Baseline to end of study drug therapy (up to 65 weeks).
Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) at or After 16 Weeks on Study
The number of participants whose best response was CR, PR or SD (per the RECIST) at or after 16 weeks on study: CR: disappearance of all target/non-target lesions; PR: \>=30% decrease in the sum of the LDs of target lesions relative to baseline sum LD; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; PD: appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
Time frame: Baseline to 16 weeks.
Percentage of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) at or After 16 Weeks on Study
The percentage of participants whose best response was CR, PR or SD (per the RECIST) at or after 16 weeks on study: CR: disappearance of all target/non-target lesions; PR: \>=30% decrease in the sum of the LDs of target lesions relative to baseline sum LD; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; PD: appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
The Bronx, New York, United States
University Of Texas Md Anderson Cancer Ctr
Houston, Texas, United States
Local Institution
Paris, France
Local Institution
Toulouse, France
Local Institution
Modena, Italy
Local Institution
Barcelona, Spain
Local Institution
Lleida, Spain
Time frame: Baseline to 16 weeks
Proportion of Participants With Progression-Free Survival (PFS) at Weeks 9, 17, and 25
PFS:time from first dose until the date that progressive disease (PD) or clinical PD (cPD) observed,per RECIST criteria.PD:appearance of new lesion/s,or \>=20% increase in the sum of the LD of target lesions,relative to smallest sum LD recorded since treatment start,or unequivocal progression of existing non-target lesions;cPD:deterioration related to disease requiring treatment discontinuation,but without radiographic PD.Participants who died without PD were considered to have PD on the date of death.For participants who neither progressed nor died,date of the last tumor assessment was used.
Time frame: Weeks 9, 17, and 25
Mean Number of Weeks of Complete Response (CR) or Partial Response (PR)
Mean number of weeks of CR/PR (time from first date of CR/PR until first date PD observed. Tumor response defined per RECIST: CR: disappearance of all target/non-target lesions; PR: \>=30% decrease in sum of LDs of target lesions relative to baseline sum LD; PD: appearance of new lesion or \>=20% increase in sum of LD of target lesions relative to smallest sum LD or unequivocal progression of existing non-target lesions. Participants who died without reported PD were considered to have PD on date of death. For participants who neither progressed nor died, date of last tumor assessment used.
Time frame: Baseline to end of study drug therapy (up to 53.86 weeks)
Mean Plasma Concentration at Week 3
Mean plasma concentration was obtained directly from the concentration-time data.
Time frame: At pre-dose and 1, 3, 6 and 12 hours after each dose administration
Mean Plasma Concentration at Week 7
Mean plasma concentration was obtained directly from the concentration-time data.
Time frame: At pre-dose and 1, 3, 6 and 12 hours after each dose administration
Mean Change in Concentration of Collagen Type IV From Baseline
Collagen Type IV is a measure of anti-angiogenic activity. Plasma samples for assessment of change in concentration of Collagen Type IV were obtained and analyzed by enzyme-linked immunosorbent assay.
Time frame: Baseline, Week 3 and Week 5
Mean Change in Concentration of Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) From Baseline
VEGFR2 is a measure of anti-angiogenic activity. Plasma samples for assessment of change in concentration of VEGFR2 were obtained and analyzed by enzyme-linked immunosorbent assay.
Time frame: Baseline, Week 3 and Week 5
Percentage Change in Tumor Biomarkers
Tumor markers are indicators of tumor activity which may be used to predict clinical benefit and circulating biomarkers may reveal key mechanisms of action. Tissue staining was performed for caveolin, phospho-caveolin, EphA2 and insulin-like growth factor binding protein 2 (IGFBP2) markers using immunohistochemistry assays.
Time frame: Baseline
Profiling of Messenger-ribonucleic Acid (mRNA) Expression: mRNA Signal Intensity
Pharmacogenomic analysis included the assessment of the relationship between clinical benefit and mRNA expression levels and between clinical benefit and protein phosphorylation. Tumor mRNA expression was analyzed in all available tissues. mRNA was extracted from 96 formalin-fixed paraffin-embedded tissue (FFPET) samples, amplified, and fluorescently labeled. Gene expression profiling was conducted using Affymetrix Human Genome U133A 2.0 DNA microarrays. mRNA expression is reported as quantile normalized RMA values.
Time frame: Baseline
Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs) or Adverse Events (AEs)
An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition (even if not caused by the study drug). An SAE was defined as an AE that resulted in death, was life-threatening, required hospitalization (or prolongation of existing hospitalization), or was an important medical event.
Time frame: From start of study drug therapy up to 30 days after the last dose.
Number of Participants Who Experienced Drug-related SAEs, Drug-related AEs, Drug-related Grade 3 AEs and Discontinuations Due to Drug-related AEs
AE=any new untoward medical occurrence/worsening of pre-existing medical condition.SAE=AE that resulted in death, was life-threatening, required hospitalization (or prolongation of existing hospitalization), or was an important medical event. Drug-related SAEs or AEs are those events with relationship to study therapy of certain, probable or possible.AEs were graded using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC), v3: Grade 1=mild, 2=moderate, 3=severe, 4=life threatening, 5=death.Participants who discontinued the study due to any drug-related AEs were also recorded.
Time frame: From start of study drug therapy up to 30 days after the last dose.
Most Frequent Drug-related Adverse Events (AEs)
Most frequent drug-related AEs are those AEs with frequency \>=25% in either group. Drug-related AEs are those events with relationship to study therapy of certain, probable or possible.
Time frame: From start of study drug therapy up to 30 days after the last dose.
Number of Participants With Grade 3 or 4 Abnormalities in Hematology Measurements
Abnormalities were graded according to the NCI CTC, version 3.0: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening. Grades 3 and 4 criteria are defined as follows: Granulocytes: Grade 3 \<1.0 - 0.5 x 10\^9/L; Grade 4, \<0.5 x 10\^9/L. Hemoglobin: Grade 3, \<8.0 - 6.5 g/dL; Grade 4, \<6.5 g/dL. Platelets: Grade 3, \<50.0 - 25.0 x 10\^9/L; Grade 4, \<25.0 x 10\^9/L. Leukocytes: Grade 3, \<2.0 - 1.0 x 10\^9/L; Grade 4, \<1.0 x 10\^9/L.
Time frame: Throughout study, from start of study drug therapy up to 30 days after the last dose.
Number of Participants With Abnormalities (Grade 1 or 2) in Prothrombin Time (PT)
PT is a measure of the clotting ability of the blood. Abnormalities were graded according to the NCI CTC, version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening and 5=death.
Time frame: Throughout study, from start of study drug therapy up to 30 days after the last dose.
Number of Participants With Abnormalities (Grade 1 or 2) in Partial Thromboplastin Time (PTT)
PTT is a measure of the clotting ability of the blood. Abnormalities were graded according to the NCI CTC, version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening and 5=death.
Time frame: Throughout study, from start of study drug therapy up to 30 days after the last dose.
Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase
Abnormalities were graded according to the NCI CTC, version 3.0: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening. Grade 3 and 4 criteria are defined as follows: ALT, AST and alkaline phosphatase: Grade 3: \>5-20 x upper limit of normal (ULN), Grade 4: \>20 x ULN.
Time frame: Throughout study, from start of study drug therapy up to 30 days after the last dose.
Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Calcium, Potassium, Magnesium and Sodium
Abnormalities were graded according to the NCI CTC, version 3.0: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening. Grade 3 and 4 criteria are defined as follows: Calcium: Grade 3-4 : \<6.0 - \<7.0 or \>12.5 - \>13.5 mg/dL, Potassium: Grade 3-4 : \<2.5 - \<3.0 or \>6.0 - \>7.0 mEq/L, Magnesium: Grade 3-4 : \<0.6 - \<0.8 or \>2.46 - \>6.6 mEq/L, Sodium:\< 120- 130 or \>155 - \>160 mEq/L.
Time frame: Throughout study, from start of study drug therapy up to 30 days after the last dose.
Number of Participants With Grade 3 or 4 Serum Chemistry Abnormalities in Creatinine, Bicarbonate, Inorganic Phosphorous and Bilirubin (Total).
Abnormalities were graded according to the NCI CTC, version 3.0: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening. Grade 3 and 4 criteria are defined as follows: Creatinine: Grade 3-4 : \> 3.0 -6.0 ULN (upper limit of normal),Bicarbonate: Grade 3-4: \<16 -\<22 mEq/L, Phosphorous: Grade 3-4 : \<1.0 - \<2.0 mg/dL, Bilirubin, total: Grade 3-4: \>3.0 - \>10.0 ULN.
Time frame: Throughout study, from start of study drug therapy up to 30 days after the last dose.
Number of Participants With Identified Electrocardiogram (ECG) Abnormalities
ECGs were performed and all recordings were evaluated by the investigator. Abnormalities, if present at any study time point, were listed. The following ECG variables were collected: heart rate, PR interval, QRS width, and QT interval. Abnormalities in ECGs were defined by reference to institutional reports.
Time frame: Baseline, Weeks 3, 9, 17 and 25, then every 8 weeks until the end of study treatment (up to 17 weeks).
Number of Participants With Abnormal Vital Signs Measurements
Vital signs included systolic and diastolic blood pressure and heart rate. The investigator used his or her judgement to decide whether or not the values were abnormal.
Time frame: At each study visit (Week 3, 5, 7, 9, 13, 17 and 25) and end of treatment (up to 17 weeks)