E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent or progressive locally-advanced or metastatic 'triple-negative' breast cancer |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To estimate objective response rate (ORR) of dasatinib in women with recurrent or progressive locally-advanced or metastatic 'triple-negative' breast cancer. |
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E.2.2 | Secondary objectives of the trial |
1. To estimate, by subgroup, Disease Control Rate (DCR) and proportion free of progression at week 9, 17 and 25, Progression-Free Survival (PFS) distribution, and response duration 2. To determine the safety and tolerability of dasatinib in this population 3. To obtain pharmacokinetic (PK) and pharmacodynamic data 4. To obtain exploratory tumor biomarker and pharmacogenomic data |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Signed written informed consent according to institutional guidelines.
Target population 2) Invasive breast cancer based on previous biopsy, documented as negative for expression of Estrogen and Progesterone Receptor [<10% of cells stained] and for Her2/neu [IHC 0-1+ or CISH/FISH-negative] 3) A paraffin-embedded tissue block from prior surgery must be available 4) Measurable, recurrent or progressive, locally-advanced or metastatic disease assessed within 28 days prior to study drug start (see Protocol section 3.2). At least one target lesion (see Protocol section 3.3.2) must be identified. 5) Prior chemotherapy with an anthracycline, a taxane, or both (adjuvant or metastatic) 6) Zero or one chemotherapy regimen in the locally-advanced or metastatic setting 7) Recovered to Grade ≤1 from toxicities of prior therapy (except alopecia) 8) Performance status (ECOG) 0 – 1 9) Adequate organ function (CTCAE v.3.0 severity grading): a) Hepatic enzymes (AST, ALT), Total bilirubin all Grade 0 – 1 b) Serum Ca2+ ≥ Lower Limit of Normal (LLN) c) Serum K+, Mg2+, Phosphate all Grade 0 – 1 d) Creatinine Grade 0 – 2 e) Hemoglobin, Neutrophil count, Platelets, PT, PTT all Grade 0 – 1
Age and Sex 10) Females, age ≥ 18 years |
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E.4 | Principal exclusion criteria |
Sex and Reproductive Status 1) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 12 weeks after the study. 2) Women who are pregnant or breastfeeding 3) Women with a positive pregnancy test on enrollment or prior to study drug administration
Target Disease Exceptions 4) Metastatic disease confined to bone only 5) Symptomatic CNS metastasis (see section 7.2.1)
Medical History and Concurrent Diseases 6) Any anti-neoplastic therapy, including radiotherapy, or intravenous bisphosphonate within 14 days prior to study drug start 7) Prior administration of any small-molecule ‘targeted’ kinase inhibitor or any investigational agent 8) Other malignancy requiring radiotherapy or systemic treatment within 3 years 9) Concurrent medical condition which may increase the risk of toxicity, including: a) Pleural or pericardial effusion of any grade b) Clinically-significant coagulation or platelet function disorder (e.g. known von Willebrand’s disease) c) Infection requiring intravenous antibiotics d) Requirement for prohibited concomitant therapy (see section 6.4.1) e) Ongoing or recent (≤3 months) significant gastrointestinal bleeding f) Clinically-significant cardiovascular disease, including myocardial infarction or ventricular tachyarrhythmia within 6 months, prolonged QTc >450 msec. (Fridericia correction), EF <40% or major conduction abnormality (unless a cardiac pacemaker is present) g) Other medical condition which in the opinion of the Investigator might confer an unacceptable increase in risk
Other Exclusion Criteria 10) Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness 11) Inability to take oral medication for any reason 12) Inability to understand the potential risks and provide informed consent |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: Anti-tumor efficacy will be assessed by radiographic or clinical measurement. Primary analysis will be radiographically-defined Objective Response Rate (ORR) by RECIST criteria. Disease control rate (DCR) will be the key secondary efficacy endpoint and basis for interim analysis.
Safety/tolerability: Safety and tolerability is a main secondary endpoint. Adverse events will be assessed continuously and graded according to NCI Common Terminology Criteria for Adverse Events version 3.0 (CTCAEv3) for all treated subjects. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Exploratory tumor biomarker |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |