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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-023304-27 | EudraCT Number |
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| Name | Class |
|---|---|
| Bristol-Myers Squibb | INDUSTRY |
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This is a single-arm, open-label, phase I/II study. In the phase I, patients with Human Epidermal Growth Factor Receptor 2 (HER2) positive MBC will be treated with paclitaxel, trastuzumab and increasing doses of dasatinib to determine the Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT) and Recommended Phase II Dose (RPD) of the combination. Once the RPD has been identified, 48 patients will be treated at that dose to evaluate the efficacy and safety of the combination in the phase II.
Eligible patients will be enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib will be administered orally in two dose levels 100 and 140 mg once daily (a -1 dose level is included just in case dose de-escalation is needed). Treatment will be repeated on Day 1 of a 28-day cycle in all patients (both in the phase I as in the phase II) until radiographic or symptomatic progression or unacceptable toxicity occurs. Only in the phase I and in all patients included in every different dose level, the first cycle will last 38 days.
Primary Objective:
Secondary Objective(s):
Exploratory objective:
• To explore the correlation between the lymphocytosis and efficacy.
Sample Size:
Phase I: following the 3+3 rule, a minimum of 6 and a maximum of 12 patients will be recruited.
Phase II:Assuming 10% drop-out rate, 48 patients are required to enter the study.
The duration of the study, from first patient visit to last patient visit will be approximately 42 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dasatinib + trastuzumab + paclitaxel | Experimental | Eligible patients will be enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib will be administered orally in two dose levels 100 and 140 mg once daily (QD) (a -1 dose level is included just in case dose de-escalation is needed). Treatment will be repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occurs. Only in the phase I, the first cycle will last 38 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dasatinib | Drug |
|
| |
| Trastuzumab |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose Limiting Toxicity (DLT) Within the First Cycle of Dasatinib in Combination With Trastuzumab and Paclitaxel (Phase I) | DLT was defined as the occurrence of any of the following adverse events or abnormal laboratory value (graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03), assessed as possibly, probably or definitively related to study drugs, occurring within the first cycle of study treatment: Need of any dose modification within the first cycle due to toxicity, grade 3 or 4 neutropenia complicated with fever ≥38.5° C or infection, grade 4 neutropenia (absolute neutrophil count (ANC)<0.5x1000000000/L) of at least 7 days duration, grade 3 thrombocytopenia complicated by hemorrhage, grade 4 thrombocytopenia, any grade 4 non-hematologic toxicity, grade 3 non-hematologic toxicities except nausea, vomiting, or diarrhea that can be controlled by appropriate medical intervention or prophylaxis, inability to resume dosing for cycle 2 at the current dose level within 14 days due to treatment related toxicity. | Up to cycle 1 |
| Maximum Tolerated Dose (MTD) of Dasatinib in Combination With Trastuzumab and Paclitaxel (Phase I) | MTD is determined by testing increasing doses of dasatinib on dose escalation cohorts 3 to 6 patients per dose level. MTD reflects the highest dose tested in which a DLT is experienced by 0 out of 3 or 1 out of 6 patients among the dose levels | Up to cycle 1 |
| Recommended Phase II Dose (RP2D) of Dasatinib in Combination With Trastuzumab and Paclitaxel (Phase I). | The RP2D was decided by the investigators taken into consideration the information obtained in the study and based on the MTD. To define the RP2D, information about toxicity observed during the full treatment were taken into consideration (relative dose intensity and toxicity observed). | Up to cycle 1 |
| Objective Response Rate (ORR) | Tumor response was assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. ORR is defined as the percentage of patients with a Complete Response (CR) or Partial Response (PR) out of the patients who had measurable disease at baseline. Per RECIST, Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as an >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
| Measure | Description | Time Frame |
|---|---|---|
| The Number of Participants Who Experienced Adverse Events (AE) | Safety was assessed by standard clinical (blood pressure, pulse and body temperature, electrocardiogram (ECG), left ventricular ejection fraction (LVEF)) and laboratory tests (hematology: hemoglobin, platelet count, red blood cells (RBC), white blood cells (WBC) with differential (neutrophils) and absolute lymphocyte count, and serum chemistry: alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, creatinine, sodium, potassium, magnesium, phosphate and calcium). Adverse events grade were defined by the NCI CTCAE v 4.03. |
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Inclusion Criteria:
Female with histologically confirmed breast cancer with documented metastasis.
Patients must have Human Epidermal Growth Factor Receptor 2 (HER2) overexpression by immunohistochemistry (3+, HercepTest®; DAKO) or a positive fluorescence in situ hybridization for HER2 amplification evaluated by central laboratory. It is recommended that a formalin-fixed paraffin embedded (FFPE) tumor tissue block from the metastatic site (or the primary tumor, if metastatic site not available) required for HER2 testing are provided.
Patients can have measurable or non measurable disease for the Phase I part. For the Phase II only patients with measurable disease defined per RECIST 1.1 will be included.
Signed Written Informed Consent.
Target Population:
Patients with Performance Status (ECOG) of 0 or 1.
Number of previous therapies allowed or previous therapies may have included:
Adequate Organ Function (...).
Ability to take oral medication (dasatinib must be swallowed whole).
Concomitant Medications
i) Patient agrees to discontinue St. Johns Wort while receiving dasatinib therapy (discontinue St. Johns Wort at least 5 days before starting dasatinib) ii) Biphosphonates must not be initiated within 28 days prior to study therapy
Age and sex:
f) Patient, age 18 years old. g) Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 4 weeks after the last dose of study drug to minimize the risk of pregnancy. (...)
Exclusion Criteria:
Sex and reproductive status:
Target Disease Exceptions:
a) Central nervous system (CNS) metastases which are not well controlled. Eligible patients must be asymptomatic, cannot be receiving steroids or anticancer treatment, and must be enrolled at least 1 month after the end of the radiotherapy treatment
Medical History and Concurrent Diseases
i) Uncontrolled angina, congestive heart failure or myocardial infarction (MI) within (6 months) ii). Patients with intercurrent cardiac dysfunction or left ventricular ejection fraction (LVEF) < 50%.
iii) Diagnosed congenital long QT syndrome. iv) Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes).
v) Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (450 msec).
vi) Patients with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration.
d) History of significant bleeding disorder unrelated to cancer, including: i) Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease). ii) Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies).
iii) Ongoing or recent (≤ 3 months) significant gastrointestinal bleeding.
Allergies and Adverse Drug Reactions
a) Patients with known allergy to any of the study drugs or their components.
Prohibited Treatments and/or Therapies
a) Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Patients must discontinue drug 7 days prior to starting dasatinib) i) quinidine, procainamide, disopyramide ii) amiodarone, sotalol, ibutilide, dofetilide iii) erythromycin, clarithromycin iv) chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide v) cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.
b) Concurrent anti-cancer therapy c) Potent CYP3A4 inhibitors
Other exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Complejo Hospitalario Universitario de Albacete | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Instituto Catalán de Oncología de Barcelona (Hospital Duran i Reynalds) | L'Hospitalet de Llobregat | Barcelona | 08907 | Spain | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30607629 | Result | Ocana A, Gil-Martin M, Antolin S, Atienza M, Montano A, Ribelles N, Urruticoechea A, Falcon A, Pernas S, Orlando J, Montero JC, Escudero MJ, Benito S, Caballero R, Carrasco E, Rojo F, Pandiella A, Ruiz-Borrego M. Efficacy and safety of dasatinib with trastuzumab and paclitaxel in first line HER2-positive metastatic breast cancer: results from the phase II GEICAM/2010-04 study. Breast Cancer Res Treat. 2019 Apr;174(3):693-701. doi: 10.1007/s10549-018-05100-z. Epub 2019 Jan 3. | |
| 29069857 |
| Label | URL |
|---|---|
| Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research Group | View source |
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Ten patients were enrolled at the phase I receiving at least one cycle of the combination. Six patients were included at Dose Level (DL) 1 and four patients at DL 2. One patient at DL 1 and two patients at DL 2 had a DLT. Twenty-seven patients were included at the phase II.
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| ID | Title | Description |
|---|---|---|
| FG000 | Dasatinib 100mg + Trastuzumab 2mg/kg + Paclitaxel 80mg/m2 | Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Phase I |
|
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| Drug |
|
|
| Paclitaxel | Drug |
|
|
| Through study treatment, an average of 24 months |
| Through study treatment, an average of 24 months |
| To Evaluate the Clinical Benefit Rate (CBR) | Tumor response was assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. CBR is defined as the percentage of patients with a Complete Response (CR) or Partial Response (PR) plus stable disease lasting at least 6 months out of the efficacy population. Per RECIST, CR is defined as the disappearance of all target lesions; PR is defined as an >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | Through study treatment, an average of 24 months |
| Time to Progression (TTP) | TTP is defined as the time from the date of the first dose to the first date of objectively determined progressive disease. For patients not known to have objectively-determined progressive disease, TTP will be censored at the date of the last objective progression-free assessment. For patients who receive subsequent systemic anticancer therapy (after discontinuation from the study treatment) prior to objective disease progression, TTP will be censored at the date of last objective progression-free assessment prior to the initiation of post-discontinuation systemic anticancer therapy. | Through study treatment, an average of 24 months |
| Progression Free Survival (PFS) | PFS is defined as the time from the date of the first dose to the first date of objectively determined progressive disease or death from any cause. For patients not known to have died as of the data cut-off date and who do not have objectively-determined progressive disease, PFS will be censored at the date of the last objective progression-free assessment. For patients who receive subsequent systemic anticancer therapy (after discontinuation from the study treatment) prior to objective disease progression or death, PFS will be censored at the date of last objective progression-free assessment prior to the initiation of post-discontinuation systemic anticancer therapy. | Through study treatment, an average of 24 months |
| Response Duration (RD) | Tumor response was assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. RD is defined as the time from the date when the measurement criteria are met for complete response (CR) or partial response (PR) (whichever status is recorded first) until the date of first observation of disease progression or death occurred. Per RECIST, CR is defined as the disappearance of all target lesions; PR is defined as an >=30% decrease in the sum of the longest diameter of target lesions. For responding patients not known to have died as of the data cut-off date and who do not have progression, RD will be censored at the date of last visit with adequate assessment. For responding patients who receive subsequent anticancer therapy (after discontinuation from the study treatment) prior to progression, RD will be censored at the date of last visit with adequate assessment prior to the initiation of post-discontinuation anticancer therapy. | Through study treatment, an average of 24 months |
| Dasatinib Maximun Plasma Concentration (Cmax) Value (Pharmacokinetics (PK) Phase I) | To assess the influence of the concomitant administration of paclitaxel and trastuzumab on dasatinib PKs, we compared dasatinib exposures alone (first PK occasion: day 2 of cycle 1) or combined (second PK occasion: day 18 on cycle 1). The mean profiles of dasatinib plasma concentrations were determined by dose and PK occasion. | Cycle 1 day 2 and day 18 |
| Dasatinib Area Under the Plasma Concentration-time Curve (AUC) Value (Pharmacokinetics (PK) Phase I) | To assess the influence of the concomitant administration of paclitaxel and trastuzumab on dasatinib PKs, we compared dasatinib exposures alone (first PK occasion: day 2 of cycle 1) or combined (second PK occasion: day 18 on cycle 1). The area under the plasma concentration-time curve from time zero to 8 hours post dose (AUC0-8) were calculated in all treated patients, as the dasatinib plasmatic half-life is very short and concentrations at 24 hours post dose could only be quantified in some patients. | Cycle 1 day 2 and day 18 |
| Phosphorylated SRC (p-SRC) Protein Expression Change in Peripheral Blood Mononuclear Cells After 8 Hours of Treatment (Phase II) | Sequential peripheral blood mononuclear cells (PBMCs) on Cycle 1 Day 1 before treatment and 8 hours (h) after treatment (0h and 8h) were assessed to explore changes in the expression of p-SRC proteins measured by enzyme-linked immunosorbent assay (ELISA). For ELISA analyses, a duplicate of 100 µg of the extract was used to detect p-SRC (Tyr416). ELISA is a plate-based assay technique designed for detecting and quantifying proteins. The instrumentation used for protein signal-detection is an absorbance spectrophotometer (AS), which measures Absorbance (A). A is the quantity of light absorbed by a sample. As different compounds absorb light at different wavelengths, an AS can be used to distinguish compounds by analyzing the pattern of wavelengths absorbed by a given sample. Additionally, the amount of light absorbed is directly proportional to the concentration of absorbing compounds in that sample, so an AS can also be used to determine concentrations of compounds in the sample. | Cycle 1 day 1 at 0 hours and at 8 hours |
| Phosphorylated AKT (p-AKT) Protein Expression Change in Peripheral Blood Mononuclear Cells After 8 Hours of Treatment (Phase II) | Sequential peripheral blood mononuclear cells (PBMCs) on Cycle 1 Day 1 before treatment and 8 hours (h) after treatment (0h and 8h) were assessed to explore changes in the expression of p-AKT proteins measured by enzyme-linked immunosorbent assay (ELISA). For ELISA analyses, a duplicate of 100 µg of the extract was used to detect p-AKT (Ser473). ELISA is a plate-based assay technique designed for detecting and quantifying proteins. The instrumentation used for protein signal-detection is an absorbance spectrophotometer (AS), which measures Absorbance (A). A is the quantity of light absorbed by a sample. As different compounds absorb light at different wavelengths, an AS can be used to distinguish compounds by analyzing the pattern of wavelengths absorbed by a given sample. Additionally, the amount of light absorbed is directly proportional to the concentration of absorbing compounds in that sample, so an AS can also be used to determine concentrations of compounds in the sample. | Cycle 1 day 1 at 0 hours and at 8 hours |
| Phosphorylation Status of Phosphorylated SRC (p-SRC) in Skin After Treatment (Phase I) | p-SRC was analyzed in the skin biopsies taken at cycle 1 day 1 at 0 hours and 8 hours, cycle 1 day 4 and cycle 2 day 1, only in patients accepting to participate. A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300. Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of SRC. | Cycle 1 day 1 at 0 hours and at 8 hours, cycle 1 day 4 and cycle 2 day 1 |
| Phosphorylation Status of Phosphorylated SRC (p-SRC) in Skin After Treatment (Phase II) | p-SRC was analyzed in the skin biopsies taken at cycle 1 day 1 at 0 hours and 8 hours, only in patients accepting to participate. A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300. Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of SRC. | Cycle 1 day 1 at 0 hours and at 8 hours |
| Phosphorylation Status of Phosphorylated AKT (p-AKT) in Skin After Treatment (Phase I) | p-AKT was analyzed in the skin biopsies taken at cycle 1, day 1 at 0 hours and 8 hours, and cycle 2 day 1, only in patients accepting to participate. A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300. Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of AKT | Cycle 1 day 1 at 0 hours and at 8 hours and cycle 2 day 1 |
| Phosphorylation Status of Phosphorylated AKT (p-AKT) in Skin After Treatment (Phase II) | p-AKT was analyzed in the skin biopsies taken at cycle 1, day 1 at 0 hours and 8 hours, only in patients accepting to participate. A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300. Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of AKT | Cycle 1 day 1 at 0 hours and at 8 hours |
| Phosphorylation Status of Phosphorylated ERK (p-ERK) in Skin After Treatment (Phase I) | p-ERK was analyzed in the skin biopsies taken at cycle 1 day 1 at 0 hours and 8 hours, cycle 1 day 4 at 8 hours, and cycle 2 day 1 at 8 hours, only in patients accepting to participate. A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300. Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of ERK | Cycle 1 day 1 at 0 hours and at 8 hours, cycle 1 day 4 at 8 hours and cycle 2 day 1 at 8 hours |
| Phosphorylation Status of Phosphorylated ERK (p-ERK) in Skin After Treatment (Phase II) | Phosphorylated extracellular signal-regulated kinases (p-ERK) 1 and 2 expression were analyzed in the skin biopsies taken at the cycle 1 day 1 at 0 hours and 8 hours, only in patients accepting to participate. A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300. Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of ERK | Cycle 1 day 1 at 0 hours and at 8 hours |
| Number of Participants With Correlation Between Lymphocytosis and Efficacy. | Efficacy (ORR, CBR, TTP, RD and PFS) was assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria, and were correlated Lymphocytes, that were measured in the weekly hematology analyses performed within the first cycle. | Cycle 1 |
| Hospital Alvaro Cunqueiro |
| Vigo |
| Pontevedra |
| 36204 |
| Spain |
| Complejo Hospitalario Universitario A Coruña | A Coruña | 15006 | Spain |
| Hospital Clinic i Provincial | Barcelona | 08036 | Spain |
| Hospital General Universitario Gregorio Marañón | Madrid | 28007 | Spain |
| Hospital Clínico Universitario Virgen de la Victoria | Málaga | 29010 | Spain |
| Hospital Universitario Virgen del Rocío | Seville | 41013 | Spain |
| Instituto Valenciano de Oncología | Valencia | 46009 | Spain |
| Result |
| Ocana A, Gil-Martin M, Martin M, Rojo F, Antolin S, Guerrero A, Trigo JM, Munoz M, Pandiella A, Diego NG, Bezares S, Caballero R, Carrasco E, Urruticoechea A. A phase I study of the SRC kinase inhibitor dasatinib with trastuzumab and paclitaxel as first line therapy for patients with HER2-overexpressing advanced breast cancer. GEICAM/2010-04 study. Oncotarget. 2017 Apr 14;8(42):73144-73153. doi: 10.18632/oncotarget.17113. eCollection 2017 Sep 22. |
| FG001 | Dasatinib 140mg + Trastuzumab 2mg/kg + Paclitaxel 80mg/m2 | Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days. |
| FG002 | Dasatinib 70mg + Trastuzumab 2mg/kg + Paclitaxel 80mg/m2 | Cohort 3: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 70mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days. |
| FG003 | PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 | Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Phase II |
|
|
Two patients from phase I with measurable disease and RP2D 100mg were included in the phase II analyses, and there is only one statistical analysis with this population of 29 patients (27 patients from phase II + 2 patients from phase I) for phase II.
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| ID | Title | Description |
|---|---|---|
| BG000 | Dasatinib 100mg + Trastuzumab 2mg/kg + Paclitaxel 80mg/m2 | Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days. |
| BG001 | Dasatinib 140mg + Trastuzumab 2mg/kg + Paclitaxel 80mg/m2 | Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days. |
| BG002 | PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 | Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
| ||||||||||||||||
| Menopausal Status | Count of Participants | Participants |
| ||||||||||||||||
| Eastern Cooperative Oncology Group (ECOG) status | Measure Description: ECOG score runs from 0 to 5, with 0 denoting perfect health and 5 death. 0 - Asymptomatic
| Count of Participants | Participants |
| |||||||||||||||
| Hormonal Receptor | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Dose Limiting Toxicity (DLT) Within the First Cycle of Dasatinib in Combination With Trastuzumab and Paclitaxel (Phase I) | DLT was defined as the occurrence of any of the following adverse events or abnormal laboratory value (graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03), assessed as possibly, probably or definitively related to study drugs, occurring within the first cycle of study treatment: Need of any dose modification within the first cycle due to toxicity, grade 3 or 4 neutropenia complicated with fever ≥38.5° C or infection, grade 4 neutropenia (absolute neutrophil count (ANC)<0.5x1000000000/L) of at least 7 days duration, grade 3 thrombocytopenia complicated by hemorrhage, grade 4 thrombocytopenia, any grade 4 non-hematologic toxicity, grade 3 non-hematologic toxicities except nausea, vomiting, or diarrhea that can be controlled by appropriate medical intervention or prophylaxis, inability to resume dosing for cycle 2 at the current dose level within 14 days due to treatment related toxicity. | Posted | Count of Participants | Participants | Up to cycle 1 |
|
|
| ||||||||||||||||||||||||||||||
| Primary | Maximum Tolerated Dose (MTD) of Dasatinib in Combination With Trastuzumab and Paclitaxel (Phase I) | MTD is determined by testing increasing doses of dasatinib on dose escalation cohorts 3 to 6 patients per dose level. MTD reflects the highest dose tested in which a DLT is experienced by 0 out of 3 or 1 out of 6 patients among the dose levels | Posted | Number | mg | Up to cycle 1 |
|
| |||||||||||||||||||||||||||||||
| Primary | Recommended Phase II Dose (RP2D) of Dasatinib in Combination With Trastuzumab and Paclitaxel (Phase I). | The RP2D was decided by the investigators taken into consideration the information obtained in the study and based on the MTD. To define the RP2D, information about toxicity observed during the full treatment were taken into consideration (relative dose intensity and toxicity observed). | Posted | Number | mg | Up to cycle 1 |
|
| |||||||||||||||||||||||||||||||
| Primary | Objective Response Rate (ORR) | Tumor response was assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. ORR is defined as the percentage of patients with a Complete Response (CR) or Partial Response (PR) out of the patients who had measurable disease at baseline. Per RECIST, Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as an >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | Posted | Count of Participants | Participants | Through study treatment, an average of 24 months |
|
| |||||||||||||||||||||||||||||||
| Secondary | The Number of Participants Who Experienced Adverse Events (AE) | Safety was assessed by standard clinical (blood pressure, pulse and body temperature, electrocardiogram (ECG), left ventricular ejection fraction (LVEF)) and laboratory tests (hematology: hemoglobin, platelet count, red blood cells (RBC), white blood cells (WBC) with differential (neutrophils) and absolute lymphocyte count, and serum chemistry: alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, creatinine, sodium, potassium, magnesium, phosphate and calcium). Adverse events grade were defined by the NCI CTCAE v 4.03. | Posted | Count of Participants | Participants | Through study treatment, an average of 24 months |
| ||||||||||||||||||||||||||||||||
| Secondary | To Evaluate the Clinical Benefit Rate (CBR) | Tumor response was assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. CBR is defined as the percentage of patients with a Complete Response (CR) or Partial Response (PR) plus stable disease lasting at least 6 months out of the efficacy population. Per RECIST, CR is defined as the disappearance of all target lesions; PR is defined as an >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | Posted | Count of Participants | Participants | Through study treatment, an average of 24 months |
|
| |||||||||||||||||||||||||||||||
| Secondary | Time to Progression (TTP) | TTP is defined as the time from the date of the first dose to the first date of objectively determined progressive disease. For patients not known to have objectively-determined progressive disease, TTP will be censored at the date of the last objective progression-free assessment. For patients who receive subsequent systemic anticancer therapy (after discontinuation from the study treatment) prior to objective disease progression, TTP will be censored at the date of last objective progression-free assessment prior to the initiation of post-discontinuation systemic anticancer therapy. | Posted | Median | 95% Confidence Interval | months | Through study treatment, an average of 24 months |
|
| ||||||||||||||||||||||||||||||
| Secondary | Progression Free Survival (PFS) | PFS is defined as the time from the date of the first dose to the first date of objectively determined progressive disease or death from any cause. For patients not known to have died as of the data cut-off date and who do not have objectively-determined progressive disease, PFS will be censored at the date of the last objective progression-free assessment. For patients who receive subsequent systemic anticancer therapy (after discontinuation from the study treatment) prior to objective disease progression or death, PFS will be censored at the date of last objective progression-free assessment prior to the initiation of post-discontinuation systemic anticancer therapy. | Posted | Median | 95% Confidence Interval | months | Through study treatment, an average of 24 months |
|
| ||||||||||||||||||||||||||||||
| Secondary | Response Duration (RD) | Tumor response was assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. RD is defined as the time from the date when the measurement criteria are met for complete response (CR) or partial response (PR) (whichever status is recorded first) until the date of first observation of disease progression or death occurred. Per RECIST, CR is defined as the disappearance of all target lesions; PR is defined as an >=30% decrease in the sum of the longest diameter of target lesions. For responding patients not known to have died as of the data cut-off date and who do not have progression, RD will be censored at the date of last visit with adequate assessment. For responding patients who receive subsequent anticancer therapy (after discontinuation from the study treatment) prior to progression, RD will be censored at the date of last visit with adequate assessment prior to the initiation of post-discontinuation anticancer therapy. | Posted | Median | 95% Confidence Interval | months | Through study treatment, an average of 24 months |
| |||||||||||||||||||||||||||||||
| Secondary | Dasatinib Maximun Plasma Concentration (Cmax) Value (Pharmacokinetics (PK) Phase I) | To assess the influence of the concomitant administration of paclitaxel and trastuzumab on dasatinib PKs, we compared dasatinib exposures alone (first PK occasion: day 2 of cycle 1) or combined (second PK occasion: day 18 on cycle 1). The mean profiles of dasatinib plasma concentrations were determined by dose and PK occasion. | Two participant samples for cycle 1 day 18 could not be obtained. | Posted | Mean | Standard Deviation | ng/mL | Cycle 1 day 2 and day 18 |
| ||||||||||||||||||||||||||||||
| Secondary | Dasatinib Area Under the Plasma Concentration-time Curve (AUC) Value (Pharmacokinetics (PK) Phase I) | To assess the influence of the concomitant administration of paclitaxel and trastuzumab on dasatinib PKs, we compared dasatinib exposures alone (first PK occasion: day 2 of cycle 1) or combined (second PK occasion: day 18 on cycle 1). The area under the plasma concentration-time curve from time zero to 8 hours post dose (AUC0-8) were calculated in all treated patients, as the dasatinib plasmatic half-life is very short and concentrations at 24 hours post dose could only be quantified in some patients. | Two participant samples for cycle 1 day 18 could not be obtained. | Posted | Mean | Standard Deviation | ng·h/mL | Cycle 1 day 2 and day 18 |
| ||||||||||||||||||||||||||||||
| Secondary | Phosphorylated SRC (p-SRC) Protein Expression Change in Peripheral Blood Mononuclear Cells After 8 Hours of Treatment (Phase II) | Sequential peripheral blood mononuclear cells (PBMCs) on Cycle 1 Day 1 before treatment and 8 hours (h) after treatment (0h and 8h) were assessed to explore changes in the expression of p-SRC proteins measured by enzyme-linked immunosorbent assay (ELISA). For ELISA analyses, a duplicate of 100 µg of the extract was used to detect p-SRC (Tyr416). ELISA is a plate-based assay technique designed for detecting and quantifying proteins. The instrumentation used for protein signal-detection is an absorbance spectrophotometer (AS), which measures Absorbance (A). A is the quantity of light absorbed by a sample. As different compounds absorb light at different wavelengths, an AS can be used to distinguish compounds by analyzing the pattern of wavelengths absorbed by a given sample. Additionally, the amount of light absorbed is directly proportional to the concentration of absorbing compounds in that sample, so an AS can also be used to determine concentrations of compounds in the sample. | Posted | Mean | Standard Deviation | Absorbance 450 nm | Cycle 1 day 1 at 0 hours and at 8 hours |
| |||||||||||||||||||||||||||||||
| Secondary | Phosphorylated AKT (p-AKT) Protein Expression Change in Peripheral Blood Mononuclear Cells After 8 Hours of Treatment (Phase II) | Sequential peripheral blood mononuclear cells (PBMCs) on Cycle 1 Day 1 before treatment and 8 hours (h) after treatment (0h and 8h) were assessed to explore changes in the expression of p-AKT proteins measured by enzyme-linked immunosorbent assay (ELISA). For ELISA analyses, a duplicate of 100 µg of the extract was used to detect p-AKT (Ser473). ELISA is a plate-based assay technique designed for detecting and quantifying proteins. The instrumentation used for protein signal-detection is an absorbance spectrophotometer (AS), which measures Absorbance (A). A is the quantity of light absorbed by a sample. As different compounds absorb light at different wavelengths, an AS can be used to distinguish compounds by analyzing the pattern of wavelengths absorbed by a given sample. Additionally, the amount of light absorbed is directly proportional to the concentration of absorbing compounds in that sample, so an AS can also be used to determine concentrations of compounds in the sample. | Posted | Mean | Standard Deviation | Absorbance 450 nm | Cycle 1 day 1 at 0 hours and at 8 hours |
| |||||||||||||||||||||||||||||||
| Secondary | Phosphorylation Status of Phosphorylated SRC (p-SRC) in Skin After Treatment (Phase I) | p-SRC was analyzed in the skin biopsies taken at cycle 1 day 1 at 0 hours and 8 hours, cycle 1 day 4 and cycle 2 day 1, only in patients accepting to participate. A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300. Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of SRC. | Skin biopsies could only be obtained in 5 participants at cycle 1 day 1 at 0 hours and 8 hours, cycle 1 day 4 and cycle 2 day 1. | Posted | Mean | 95% Confidence Interval | score on a scale | Cycle 1 day 1 at 0 hours and at 8 hours, cycle 1 day 4 and cycle 2 day 1 |
| ||||||||||||||||||||||||||||||
| Secondary | Phosphorylation Status of Phosphorylated SRC (p-SRC) in Skin After Treatment (Phase II) | p-SRC was analyzed in the skin biopsies taken at cycle 1 day 1 at 0 hours and 8 hours, only in patients accepting to participate. A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300. Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of SRC. | Skin biopsies could only be obtained in 6 participants at cycle 1 day 1 at 0 hours and 8 hours. | Posted | Mean | 95% Confidence Interval | score on a scale | Cycle 1 day 1 at 0 hours and at 8 hours |
| ||||||||||||||||||||||||||||||
| Secondary | Phosphorylation Status of Phosphorylated AKT (p-AKT) in Skin After Treatment (Phase I) | p-AKT was analyzed in the skin biopsies taken at cycle 1, day 1 at 0 hours and 8 hours, and cycle 2 day 1, only in patients accepting to participate. A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300. Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of AKT | Skin biopsies could only be obtained in 5 participants at cycle 1 day 1 at 0 hours and 8 hours and cycle 2 day 1. | Posted | Mean | 95% Confidence Interval | score on a scale | Cycle 1 day 1 at 0 hours and at 8 hours and cycle 2 day 1 |
| ||||||||||||||||||||||||||||||
| Secondary | Phosphorylation Status of Phosphorylated AKT (p-AKT) in Skin After Treatment (Phase II) | p-AKT was analyzed in the skin biopsies taken at cycle 1, day 1 at 0 hours and 8 hours, only in patients accepting to participate. A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300. Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of AKT | Skin biopsies could only be obtained in 6 participants at cycle 1 day 1 at 0 hours and 8 hours. | Posted | Mean | 95% Confidence Interval | score on a scale | Cycle 1 day 1 at 0 hours and at 8 hours |
| ||||||||||||||||||||||||||||||
| Secondary | Phosphorylation Status of Phosphorylated ERK (p-ERK) in Skin After Treatment (Phase I) | p-ERK was analyzed in the skin biopsies taken at cycle 1 day 1 at 0 hours and 8 hours, cycle 1 day 4 at 8 hours, and cycle 2 day 1 at 8 hours, only in patients accepting to participate. A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300. Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of ERK | Skin biopsies could only be obtained in 5 participants at cycle 1 day 1 at 0 hours and 8 hours, cycle 1 day 4 at 8 hours and cycle 2 day 1 at 8 hours. | Posted | Mean | 95% Confidence Interval | score on a scale | Cycle 1 day 1 at 0 hours and at 8 hours, cycle 1 day 4 at 8 hours and cycle 2 day 1 at 8 hours |
| ||||||||||||||||||||||||||||||
| Secondary | Phosphorylation Status of Phosphorylated ERK (p-ERK) in Skin After Treatment (Phase II) | Phosphorylated extracellular signal-regulated kinases (p-ERK) 1 and 2 expression were analyzed in the skin biopsies taken at the cycle 1 day 1 at 0 hours and 8 hours, only in patients accepting to participate. A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300. Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of ERK | Skin biopsies could only be obtained in 6 participants at cycle 1 day 1 at 0 hours and 8 hours. | Posted | Mean | 95% Confidence Interval | score on a scale | Cycle 1 day 1 at 0 hours and at 8 hours |
| ||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Correlation Between Lymphocytosis and Efficacy. | Efficacy (ORR, CBR, TTP, RD and PFS) was assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria, and were correlated Lymphocytes, that were measured in the weekly hematology analyses performed within the first cycle. | Posted | Count of Participants | Participants | Cycle 1 |
|
Through study treatment, an average of 12 months
AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dasatinib 100mg + Trastuzumab 2mg/kg + Paclitaxel 80mg/m2 | Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days. | 0 | 6 | 1 | 6 | 6 | 6 |
| EG001 | Dasatinib 140mg + Trastuzumab 2mg/kg + Paclitaxel 80mg/m2 | Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days. | 0 | 4 | 2 | 4 | 4 | 4 |
| EG002 | PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 | Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses. | 1 | 29 | 6 | 29 | 29 | 29 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 3 |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 3 |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 3 |
|
| Angina | Cardiac disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 2 |
|
| Overdose | Injury, poisoning and procedural complications | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 3. Patient took dasatinib 140mg from January 30, 2014 to March 14, 2014. No any additional AEs were observed due to this intake of higher dose of dasatinib. |
|
| Soft tissue and skin infection | Infections and infestations | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 3 |
|
| Catheter related infection | Infections and infestations | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 2 |
|
| Sudden death | General disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 5 |
|
| Febrile syndrome respiratory focus | Respiratory, thoracic and mediastinal disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alanine aminotransferase increased | Investigations | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 3 |
|
| Aspartate aminotransferase increased | Investigations | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 3 |
|
| Diarrhea | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 3 |
|
| Fatigue | General disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 3 |
|
| Hypertension | Vascular disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 3 |
|
| Hyponatremia | Metabolism and nutrition disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 3 |
|
| Tumor pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 3 |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 3 |
|
| Nausea | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 3 |
|
| Abdominal pain | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 3 |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 3 |
|
| Vomiting | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 3 |
|
| Ejection Fraction Decreased | Investigations | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 3 |
|
| Anemia | Blood and lymphatic system disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 2 |
|
| Ejection Fraction Decreased | Investigations | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 2 |
|
| Neutrophil Count Decreased | Investigations | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 2 |
|
| Neutrophil Count Decreased | Investigations | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 3 |
|
| Neutrophil Count Decreased | Investigations | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
| Weight Gain | Investigations | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 2 |
|
| Alopecia | Skin and subcutaneous tissue disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 2 |
|
| Hypocalcemia | Metabolism and nutrition disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 2 |
|
| Fatigue | General disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
| Fatigue | General disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 2 |
|
| Anorexia | Metabolism and nutrition disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 2 |
|
| Alanine Aminotransferase Increased | Investigations | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
| Aspartate Aminotransferase Increased | Investigations | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
| Red Blood Cells Count Decrease | Investigations | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
| Anemia | Blood and lymphatic system disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
| Diarrhea | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
| White Blood Cell Decreased | Investigations | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
| Lymphopenia | Investigations | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
| Cough | Respiratory, thoracic and mediastinal disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
| Fever | General disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
| Hypertension | Vascular disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
| Edema limbs | General disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
| Anorexia | Metabolism and nutrition disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
| Alkaline phosphatase increased | Investigations | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
| Headache | Nervous system disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
| Mucositis oral | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
| Nausea | Gastrointestinal disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
| Peripheral sensory neuropathy | Nervous system disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
| Activated Partial Thromboplastin Time Prolonged | Investigations | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 2 |
|
| Hypomagnesemia | Metabolism and nutrition disorders | NCI CTC-AE v 4.03 | Non-systematic Assessment | Grade 1 |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Scientific Director / Medical Lead / Project Manager | Spanish Breast Cancer Research Group | +34916592870 | geicam@geicam.org |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069439 | Dasatinib |
| D000068878 | Trastuzumab |
| D017239 | Paclitaxel |
| ID | Term |
|---|---|
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011743 | Pyrimidines |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |
Not provided
Not provided
| Physician Decision |
|
| Withdrawal by Subject |
|
| Death |
|
| Not finished treatment |
|
| Protocol Violation |
|
| Male |
|
| Hispanic |
|
| Premenopausal |
|
| Perimenopausal |
|
| ECOG 1 |
|
| Negative |
|
| Progesterone Receptor |
|
|
|
|
| OG002 | PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 | Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses. |
|
|
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| Participants |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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| Units | Counts |
|---|---|
| Participants |
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|
|
|
|
|
| OG002 | PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 | Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses. |
|
|