| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Treatment of subjects with advanced breast cancer (ABC) who have failed both a taxane and an anthracycline-containing chemotherapy regimen/s (either concurrently or sequentially) or who failed a taxane treatment and for whom further anthracycline therapy is not indicated. |
|
| 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 |
|
| 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) of subjects with advanced breast cancer receiving sunitinib malate at a starting dose of 37.5 mg orally once daily with that of capecitabine at a dose of 1250 or 1000 (in patients older than 65 years) mg/m2 twice a day for 2 consecutive weeks, followed by a 1-week rest period and given as 3 weeks cycles. |
|
| E.2.2 | Secondary objectives of the trial |
| To assess ﾕ Time to Tumor Progression (TTP) ﾕ Overall Response ﾕ Duration of Response ﾕ Time to Tumor Response ﾕ Overall Survival ﾕ Patient Reported Outcomes (PROﾒs) ﾕ Safety |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
| 1. Histologically or cytologically proven diagnosis of breast adenocarcinoma that is not amenable to surgery, radiation, or combined modality 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. Tumor must be HER 2 negative (immunostaining 0, 1+ or FISH negative) 4. Must have received prior treatment with an anthracycline and a taxane either concurrently or sequentially in the neoadjuvant, adjuvant and or/ advanced disease treatment settings. No more than 1 chemotherapy regimen in the advanced setting. 5. Must have received an adequate course of anthracyclines, considered standard for adjuvant and/or metastatic disease therapy. Prior hormonal therapy or immunotherapy in the adjuvant and/or advanced/metastatic disease settings permitted but is to be discontinued at least 3 weeks before enrollment in the study. 6. May have received prior radiation therapy. A measurable lesion that has been previously irradiated will not be considered as target lesion and will be evaluated only when it increases in size. Radiotherapy is to be completed >/=3 weeks prior to study randomization. 7. Female, 18 years of age or older. 8. ECOG performance status 0 or 1. 9. Resolution of all acute toxic effects of prior therapy or surgical procedures to grade </=1 (except alopecia). 10. Adequate organ function as defined by the following criteria: ﾕ 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 ﾕ Total serum bilirubin </=1.5 x ULN ﾕ Serum albumin >/=3.0 g/dL ﾕ Absolute neutrophil count (ANC) >/=1500/ﾵL ﾕ Platelets >/=100,000/ﾵL ﾕ Hemoglobin >/=9.0 g/dL ﾕ Serum creatinine </=1.5 x ULN or calculated creatinine clearance >/= 50 ml/min. ﾕ Left ventricular ejection fraction (LVEF) >/=50% as measured by either multigated acquisition (MUGA) scan or echocardiogram (ECHO) 11.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. 12. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. |
|
| E.4 | Principal exclusion criteria |
| 1. Prior treatment with regimens of chemotherapy in the advanced/metastatic disease setting beyond those containing anthracyclines and taxanes or multiple anthracyclines/ taxanes treatments. Any prior regimen with capecitabine 2. Major surgery, radiation therapy, or systemic therapy within 3 weeks of first study treatment. At least 7 days should elapse from the time of minor surgical procedure including placement of an access device or fine needle aspiration before randomization into this study can occur. 3. Wounds that have not completely healed, active ulcer(s), or bone fracture(s). 4. Prior high-dose chemotherapy requiring hematopoietic stem cell rescue. 5. Prior radiation therapy to >25% of the bone marrow. 6. Current treatment on another clinical trial. 7. Brain metastases, spinal cord compression, or carcinomatous meningitis, or leptomeningeal disease. 8. Bone lesions as the only manifestation of current metastatic breast cancer. 9. 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. 10. 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. 11. Ongoing cardiac dysrhythmias of NCI CTCAE grade >/=2, atrial fibrillation of any grade, or QTc interval >470 msec for females. 12. Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy). 13. Current treatment with therapeutic doses of anticoagulant (low dose Coumadin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed). Low molecular weight heparin monitored by INR is allowed. 14. Known human immunodeficiency virus infection. 15. Female patients who are pregnant or nursing, Female patients of child-bearing potential who are unwilling or unable to use adequate contraception to prevent pregnancy during the program. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to first day of study medication. 16. 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. 17. Known hypersensitivity to 5-fluorouracil or capecitbabine 18. Known dihydropyrimidine dehydrogenase deficiency. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression Free Survival (PFS) is defined as the time from date of randomization to first documentation of objective tumor progression or to death due to any cause, whichever occurs first. |
|
| 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 | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Information not present in EudraCT |
| 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 | 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) | 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.8.5 | 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 |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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
| |
| 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 |
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