E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10006187 |
E.1.2 | Term | Breast cancer |
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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 demonstrate that the combination of docetaxel with sunitinib is superior to docetaxel in prolonging PFS in patients with advanced breast cancer who have relapsed after an anthracycline-based chemotherapy in the adjuvant setting. |
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E.2.2 | Secondary objectives of the trial |
To compare the clinical benefit in patients treated with the 2 regimens. To compare the safety of the 2 regimens. To compare the patient reported outcomes of patients treated with the 2 regimens.
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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. Her-2 negative breast cancer (i.e., FISH or CISH (where approved) negative or immunohistochemistry 0 or +1). 3. Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) or bone-only disease. 4. The following patients are eligible: • Patients not candidate for adjuvant chemotherapy at first diagnosis who relapsed with distant metastases • Patients candidate for adjuvant or neo-adjuvant hormonal therapy at first diagnosis who relapsed with distant metastases. • Patients candidate for adjuvant or neo-adjuvant cytotoxic therapy at first diagnosis who relapsed with locally advanced or metastatic disease • If adjuvant or neo-adjuvant therapy included also a taxane, relapse must have occurred ≥12 months since completion of chemotherapy. • Hormonal therapy concurrent or sequential to adjuvant chemotherapy is allowed. • Hormonal therapy for advanced disease is allowed but is to be discontinued prior to the start of study treatment. 5. Must be candidate for treatment with docetaxel. 6. May have received prior radiation therapy. A measurable lesion that has been previously irradiated will be evaluated only when it increases in size. Radiotherapy is to be completed prior to screening disease assessments. 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 or other toxicities not considered a safety risk for the patient). 10. Adequate organ function as defined by the following criteria: • Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤1.5 x upper limit of normal (ULN), or AST and ALT ≤2.5 x ULN if liver function abnormalities are due to underlying malignancy. • Deleted in Amendment 2 (Alkaline phosphatase (ALP) ≤2.5 x ULN). • Total serum bilirubin <1 x ULN. [patients suffering from Gilbert’s disease are allowed to enter the study] • Serum albumin ≥2.5 g/dL. • Absolute neutrophil count (ANC) ≥1500/µL. • Platelets ≥100,000/µL. • Hemoglobin ≥8.5 g/dL. • Serum creatinine ≤1.5 x ULN. • 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. |
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E.4 | Principal exclusion criteria |
1. Clinical presentation of inflammatory carcinoma with no other measurable disease. 2. Prior treatment with chemotherapy in the metastatic disease setting. 3.Prior treatment on a sunitinib clinical trial. 4. Patients for whom docetaxel is contraindicated according to the local prescribing information. 5. History of severe hypersensitivity reactions to docetaxel or to other drugs formulated with polysorbate 80. 6. AST and/or ALT >1.5 x ULN concomitant with ALP >2.5 x ULN. 7. Major surgery, or systemic therapy (with the exception of hormonal therapy) within 3 weeks of start of study treatment. At least 1 week should elapse since minor surgical procedures including placement of an access device or fine needle aspiration. 8. Deleted in Amendment 2 (Prior high-dose chemotherapy requiring hematopoietic stem cell rescue). 9. Deleted in Amendment 2 (Prior radiation therapy to >25% of the bone marrow). 10. Current treatment on another clinical trial. 11. History or presence of brain metastases, presence of spinal cord compression, or carcinomatous meningitis, or leptomeningeal disease. 12. Diagnosis of any second malignancy within the last 3 years, except for adequately treated basal cell carcinoma or squamous cell skin cancer or in situ carcinoma of the cervix uteri. 13. Any of the following within the 6 months prior to starting study treatment: myocardial infarction, severe/unstable angina, congestive heart failure, cerebrovascular accident including transient ischemic attack, or pulmonary embolus. 14. Ongoing cardiac dysrhythmias of grade ≥2, or QTc interval >470 msec. 15. Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy). 16. Current treatment with therapeutic doses of coumarin derivatives or oral antivitamin K agents such as warfarin and phenprocoumon (low dose for deep vein thrombosis prophylaxis is allowed). Treatment with therapeutic doses of lowmolecular- weight heparin is allowed. 17. Known human immunodeficiency virus infection. 18. Pregnancy or breastfeeding. Female patients who are pregnant or nursing, female of child-bearing potential who is 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 study entry. 19. 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. Prior treatment on a sunitinib clinical trial. |
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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 | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 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 | 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.8.6 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 | 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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End of Trial in a Member State of the European Union is defined as the time at which it is deemed that sufficient patients have been recruited and completed the trial as stated in the regulatory application (i.e., Clinical Trial Application (CTA)) and ethics application in the Member State. |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |