| 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). |
|
| 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 | 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 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 |
|
| 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
• 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. Documentation of estrogen and progestin receptor (ER/PR) negative status and HER2/neu receptor negative status (ie, FISH or CISH (where approved) negative or
immunohistochemistry 0 or +1).
3. Prior treatment with an anthracycline and a taxane in the neoadjuvant, 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- or second-line advanced disease setting with
RECIST or WHO-defined disease progression documented during treatment, or, if the
patient completed treatment with objective disease response, documented disease
progression after discontinuing treatment. Patients entering the study on the basis of this criterion may have also previously received neoadjuvant or adjuvant treatment with chemotherapy.
5. Measurable or non-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. (Enrollment of patients having boneonly 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 6 of the study.)
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. Deleted in Amendment #2 (bisphosphonate therapy for metastatic bone disease must have
initiated therapy at least 3 weeks prior to first dose of treatment on study).
8. Male or female, 18 years of age or older.
9. ECOG performance status 0, 1 or 2.
10. Resolution of all acute toxic effects of prior therapy or surgical procedures to grade ≤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) ≤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
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. |
|
| E.4 | Principal exclusion criteria |
1. Deleted in Amendment #2 (histology of inflammatory carcinoma).
2. Prior treatment with ≥3 regimens of cytotoxic therapy in the advanced disease setting.
3. Prior treatment on a SU011248 clinical trial.
4. Deleted in Amendment #1 (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. Deleted in Amendment #2 (prior high-dose chemotherapy requiring hematopoietic stem cell rescue).
7. Deleted in Amendment #2 (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 contralateral breast cancer also with triple negative receptor status, adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
11. 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.
12. 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.
13. Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy).
14. Current treatment with therapeutic doses of coumarin-derivatives or oral anti-vitamin K agents such as warfarin and phenprocoumon (use of low doses 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. |
|
| 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 | Yes |
| 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) | 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 | 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 26 |
| 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
|
| 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). |
|
| 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 |
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