| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Locally Recurrent or Metastatic Breast Cancer |
|
| 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 | 10006198 |
| E.1.2 | Term | Breast cancer recurrent |
|
| 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 | 10027475 |
| E.1.2 | Term | Metastatic breast cancer |
|
| 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 |
|
| 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
|
|
| 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 or bone-only disease. (Enrollment of patients having bone-only disease is at the discretion of Principal Investigators and Institutional Review Boards/Ethics Committees at participating institutions. Patients having bone-only disease will be required to undergo an additional bone scan at week 8 of the study. Patients having bone-only disease that are hormone receptor-positive must have progressed on previous hormone 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) or other not toxicities considered a safety risk for the patient.
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 (Patients with Gilbert’s disease may not be required to meet this criterion.)
•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
•Urine protein:creatinine ratio <1
•Left ventricular ejection fraction (LVEF) equal to or above 50% as measured 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. |
|
| 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. (Hormonal therapy for advanced disease is allowed, but must be discontinued prior to the start of study treatment).
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. Deleted in Amendment #2 (prior high-dose chemotherapy).
10. Deleted in Amendment #2 (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 6 months prior to starting study treatment: myocardial infarction, severe/unstable angina, 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 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-derivatives such as warfarin and phenprocoumon (use of low dose for deep vein thrombosis prophylaxis is allowed) or oral anti-vitamin K agents. If currently receiving treatment with oral coumarin-derivatives, patients must have their PT measured and their INR monitored.
Patients with an INR >1.5 will be excluded from enrollment. Low molecular weight heparin is allowed at any dose level.
18. History of gross hemorrhage within the past 6 months (eg, hemoptysis or hematuria requiring medical intervention).
19. Known human immunodeficiency virus infection.
20. Female who is pregnant or nursing; female of child-bearing potential who is unwilling or unable to use adequate contraception to prevent pregnancy during the trial and for 90 days after the last dose of study treatment. All female patients with reproductive potential must have a negative pregnancy test (serum or urine)
prior to randomization.
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. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression-free survival (PFS) |
|
| 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 | Yes |
| 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 | 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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 10 |
| 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 | 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
|
End of Trial in a MS of the EU is defined when sufficient patients have been recruited and completed the trial as stated in the regulatory application and ethics application in the MS.
End of Trial in all participating countries is defined as the time at which all patients enrolled in the study have completed treatment on study
Patients should continue to be evaluated for safety for at least 28 calendar days after the last dose of study drug (chemotherapy or angiogenesis inhibitor) |
|
| 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 | 7 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 1 |
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