E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
metastatic HER2-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 evaluate progression-free survival (PFS) of a combination treatment with docetaxel 75 mg/m2 and sorafenib 400 mg bid every 3 weeks in subjects with MBC as per RECIST tumor response criteria. |
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E.2.2 | Secondary objectives of the trial |
- To analyze the duration of response, time to disease progression and overall survival time. - To evaluate patient reported outcome / Quality of life (FACT B) - Safety and tolerability - Correlate baseline and change in tumor and serum genetic and proteomic patterns with clinical response (optional protocol supplement)
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
translational research protocol supplement for study protocol:
Randomized, double-blind Phase II study of Docetaxel + Sorafenib (Nexavar®) versus Docetaxel + Placebo in First-Line treatment of patients with HER2-negative, metastatic breast cancer.
Final Version, 27.03.2008
Objective: The aim of this protocol to the MADONNA clinical trial is to correlate baseline and changes in serum genetic and proteomis patterns with clinical response. |
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E.3 | Principal inclusion criteria |
1. Histologically or cytologically confirmed stage IV adenocarcinoma of the breast or inoperable local relapse 2. Female patients with HER2 negative breast cancer (latest assessment) 3. Patients requiring first line mono-chemotherapy with taxanes 4. Age > 18 years. 5. ECOG Performance Status of ≤ 2 6. Life expectancy of at least 12 weeks. 7. Subjects with at least one uni-dimensional (for RECIST) measurable lesion. Lesions must be measured by CT-scan or MRI 8. No prior chemotherapy for locally recurrent or metastatic disease 9. At least 12 months since prior adjuvant or neoadjuvant taxane therapy; endocrine treatment for early breast cancer is allowed and patients may have failed hormonal therapy in the metastatic stage, if they are ER/PgR-positive. 10. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening: 11. Hemoglobin > 9.0 g/dl 12. Absolute neutrophil count (ANC) >1.500/mm3 13. Platelet count 100.000/μl 14. Total bilirubin < 1,0 times the upper limit of normal 15. ALT and AST < 2,5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer) 16. Alkaline phosphatase < 4 x ULN 17. PT-INR/PTT < 1.5 x upper limit of normal [Patients who are being therapeutically anticoagulated with an agent such as coumarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.] 18. Serum creatinine < 1.5 x upper limit of normal. 19. Signed and dated informed consent before the start of specific protocol procedures.
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E.4 | Principal exclusion criteria |
1. History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension. 2. History of HIV infection or chronic hepatitis B or C 3. Active clinically serious infections (> grade 2 NCI-CTC version 3.0) 4. Prior radiological or clinical evidence of CNS metastases including previously treated, resected, or asymptomatic brain lesions or leptomeningeal involvement by head CT scan or MRI 5. Patients with seizure disorder requiring medication (such as steroids or anti-epileptics) 6. History of organ allograft 7. Patients with evidence or history of bleeding diathesis 8. Patients undergoing renal dialysis 9. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry. Excluded therapies and medications, previous and concomitant: 10. Anticancer chemotherapy or immunotherapy (including mistletoe) during the study or within 3 weeks of study entry. Hormone therapy parallel to study treatment is not allowed, but no wash-out period is necessary. 11. Radiotherapy during study or within 3 weeks of start of study drug. (Palliative radiotherapy of non-target lesions will be allowed). 12. Major surgery within 4 weeks of start of study 13. Autologous bone marrow transplant or stem cell rescue within 4 months of study 14. Use of biologic response modifiers, such as G-CSF, within 3 week of study entry. [G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator; however they may not be substituted for a required dose reduction.] [Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study] 15. Investigational drug therapy outside of this trial during or within 4 weeks of study entry 16. Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Women enrolled in this trial must use adequate barrier birth control measures during the course of the trial. 17. Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results 18. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study 19. Patients unable to swallow oral medications.
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival |
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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 | No |
E.6.7 | Pharmacodynamic | No |
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 | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 40 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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 | 5 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |