E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally Recurrent or Metastatic Breast Cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055113 |
E.1.2 | Term | Breast cancer metastatic |
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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 compare the progression-free survival (PFS) for patients having locally recurrent or metastatic BC who receive SU011248 plus paclitaxel versus bevacizumab plus paclitaxel |
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E.2.2 | Secondary objectives of the trial |
· To compare the safety of SU011248 plus paclitaxel versus bevacizumab plus paclitaxel in this patient population · To compare measures of duration of tumor control and overall survival · To assess patient reported outcomes of health-related quality of life and disease-related symptoms · To assess measurement and valuation of health status · To explore the relationship between specific biomarkers and cancer- and treatment-related outcomes |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically or cytologically proven diagnosis of breast cancer with evidence of 1) unresectable, locally recurrent, or 2) metastatic disease. Locally recurrent disease must not be amenable to resection OR radiation therapy with curative intent. 2. Measurable disease as per RECIST. Measurable lesions that have been previously radiated will not be considered target lesions unless increase in size has been observed following completion of radiation therapy. 3. Male or female, 18 years of age or older. 4. ECOG performance status 0 or 1. 5. Resolution of all acute toxic effects of prior therapy or surgical procedures to grade </=1 (except alopecia). 6. Adequate organ function as defined by the following criteria: · Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) </=2.5 x upper limit of normal (ULN), or AST and ALT </=5 x ULN if liver function abnormalities are due to underlying malignancy · Total serum bilirubin </=1.5 x ULN · Serum albumin >/=3.0 g/dL · Absolute neutrophil count (ANC) >/=1500/mL · Platelets >/=100,000/mL · Hemoglobin >/=9.0 g/dL · Serum creatinine </=1.5 x ULN · Urine protein:creatinine ratio <1 · Left ventricular ejection fraction (LVEF) above the lower limit of normal (LLN) as assessed by either multigated acquisition (MUGA) scan or echocardiogram (ECHO). 7. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment. 8. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. |
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E.4 | Principal exclusion criteria |
1. HER2/neu positive disease unless trastuzumab was previously received and the patient experience progression or trastuzumab was contraindicated. 2. Receipt of a taxane in the adjuvant setting unless disease free interval >/=12 months after end of treatment. 3. Prior treatment with bevacizumab or SU011248. 4. Prior treatment with cytotoxic anti-cancer therapies in the advanced disease setting. 5. History of dose-limiting hypersensitivity reactions to paclitaxel, Cremophor EL, Chinese hamster ovary cell product or other recombinant human antibodies. 6. Radiation therapy within 2 weeks of first study treatment. 7. Major surgery within 4 weeks of first study treatment. At least 7 days should elapse from the time of minor surgical procedure including placement of an access device. 8. Wounds that have not completely healed, active ulcer(s), or bone fracture(s). 9. Prior high-dose chemotherapy requiring hematopoietic stem cell rescue. 10. Prior radiation therapy to >25% of the bone marrow. 11. Current treatment on another clinical trial. 12. Presence of brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease. 13. Diagnosis of any second malignancy within the last 3 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix. 14. Any of the following within the 12 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischemic attack, pulmonary embolus, deep vein thrombosis or other significant thromboembolic events. 15. Ongoing cardiac dysrhythmias of NCI CTCAE grade >/=2, atrial fibrillation of any grade, or QTc interval >450 msec for males or >470 msec for females. 16. Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy). 17. Current treatment with therapeutic doses of coumarin-derived anticoagulant (low dose Coumadin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed). 18. History of gross hemorrhage within the past 6 months (eg, hemoptysis or hematuria requiring medical intervention). 19. Known human immunodeficiency virus infection. 20. Pregnancy or breastfeeding. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to first day of study medication. 21. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
· Progression-free survival (PFS) |
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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 | No |
E.6.11 | Pharmacogenomic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |