E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Histologically or cytologically proven diagnosis of breast cancer with evidence of 1) unresectable, locally recurrent, or 2) metastatic disease. Documentation of estrogen and progestin receptor (ER/PR) negative status and HER2/neu receptor negative status (ie, FISH negative or immunohistochemistry 0 or +1). |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.1 |
E.1.2 | Level | LLY |
E.1.2 | Classification code | 10055113 |
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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 for SU011248 versus standard-of-care therapy in patients with previously treated, triple receptor negative (ER/PR and HER2/neu), locally recurrent or metastatic breast cancer . |
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E.2.2 | Secondary objectives of the trial |
• To assess the safety of SU011248 versus standard-of-care in this patient population • To assess measures of duration of tumor control and overall survival • To assess patient reported outcomes • To determine SU011248 and SU012662 (active metabolite of SU011248) trough plasma concentrations (Ctrough) and to potentially explore the relationship between Ctrough, efficacy, and safety
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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 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. Documentation of estrogen and progestin receptor (ER/PR) negative status and HER2/neu receptor negative status (ie, FISH negative or immunohistochemistry 0 or +1). 3. Prior treatment with an anthracycline and a taxane in the adjuvant or metastatic disease setting. 4. Prior treatment with chemotherapy as follows: • Receipt of adjuvant chemotherapy with RECIST or World Health Organization (WHO)-defined disease progression documented during treatment or disease relapse within 6 months of last treatment, OR • Receipt of chemotherapy in the first-line advanced disease setting with RECIST or WHO-defined disease progression documented during treatment, or, if the patient completed treatment with objective disease response, disease progression documented within 3 months after discontinuing treatment. Patients entering the study on the basis of this criterion may have also previously received adjuvant treatment with chemotherapy. 5. 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. 6. Candidate for treatment with one of the standard chemotherapy regimens listed if patient is randomized to the control arm. Safety precautions standard for specific chemotherapy regimens but not stated in study entry criteria must be ensured by the investigator prior to randomization. Examples include precautions for some chemotherapy regimens based on moderately elevated liver function tests and prior hypersensitivity to an agent. 7. Patients receiving bisphosphonate therapy for metastatic bone disease must have initiated therapy at least 4 weeks prior to first dose of treatment on study. 8. Male or Female, 18 years of age or older. 9. ECOG performance status 0 or 1. 10. Resolution of all acute toxic effects of prior therapy or surgical procedures to grade less tha/equal to 1 (except alopecia). 11. The definitions of minimum adequacy for organ function required prior to study entry are as follows. In addition, safety precautions provided in the product labeling for the anticipated control arm chemotherapy must be observed. • Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) less than/equal to 2.5 x upper limit of normal (ULN), or AST and ALT less than/equal to 5 x ULN if liver function abnormalities are due to underlying malignancy • Total serum bilirubin less than/equal to 1.5 x ULN • Serum albumin major than/equal to 3.0 g/dL • Absolute neutrophil count (ANC) major than/equal to 1500/microL • Platelets major than/equal to 100,000/microL • Hemoglobin major than/equal to 9.0 g/dL • Serum creatinine less than/equal to 1.5 x ULN 12. 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. 13. 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. Histology of inflammatory carcinoma. 2. Prior treatment with omore than/ equal to2 regimens of cytotoxic therapy in the advanced disease setting. 3. Prior treatment on a SU011248 clinical trial. 4. Prior treatment with any tyrosine kinase inhibitors, VEGF inhibitors, or other angiogenic inhibitors. 5. Major surgery, radiation therapy, or systemic therapy within 3 weeks of study randomization except palliative radiotherapy to non-target metastatic lesions. 6. Prior high-dose chemotherapy requiring hematopoietic stem cell rescue. 7. Prior radiation therapy to >25% of the bone marrow. 8. Current treatment on another clinical trial. 9. Uncontrolled brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease. Patients should have completed surgery or radiation therapy for existing brain metastases, should not have documented increase in size over the previous 3 months prior to first dose of treatment on study and should be asymptomatic. 10. 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. 11. 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, or pulmonary embolus. 12. Ongoing cardiac dysrhythmias of NCI CTCAE grade major than/equal to 2, atrial fibrillation of any grade, or QTc interval >470 msec 13. Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy). 14. Current treatment with therapeutic doses of Coumadin (low dose Coumadin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed). 15. Known human immunodeficiency virus infection. 16. Pregnancy or breastfeeding. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to randomization. 17. 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 | Information not present in EudraCT |
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) | 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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 |
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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
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Treatment on study will continue until disease progression is documented according to the Response Evaluation Criteria in Solid Tumors (RECIST) or it is in the best interest of the patient to discontinue as judged by the investigator (decisions may be based on achievement of maximum benefit or tolerability issues). |
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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 | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 10 |