| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Histologically or cytologically proven diagnosis of breast adenocarcinoma that is not amenable to surgery, radiation, or combined modality therapy with curative intent |
|
| 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
• Time to Tumor Progression (TTP)
• Overall Response
• Duration of Response
• Time to Tumor Response
• Overall Survival
• Patient Reported Outcomes (PRO’s)
• Safety
of sunitinib malate at a starting dose of 37.5 mg orally once daily and of capecitabine at a dose of 1,250 or 1,000 (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.2.3 | Trial contains a sub-study | No |
| 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 score of 0, 1+ or FISH negative, CISH can replace either test where approved; if more than one test was done, the result of the FISH test should be used)
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 2 chemotherapy regimens in the
advanced disease setting.
5. Must have received an adequate course of anthracyclines, considered standard
for adjuvant and/or metastatic disease unless further anthracycline therapy is
not indicated. Prior hormonal therapy or immunotherapy in the adjuvant and/or
advanced/metastatic disease settings are permitted. Immunotherapy is to be discontinued at least 3 weeks before start of study treatment. Hormonal therapy is to be discontinued prior to the start of study treatment.
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 prior to screening disease assessments.
7. Female, 18 years of age or older. Per Amendment #4 (Japan only), subjects under age of 20 are not considered adults and will require a legal representative to supply consent.
8. ECOG performance status 0, 1 or 2.
9. Resolution of all acute toxic effects of prior therapy or surgical procedures to
grade minor than/equal to 1 (except alopecia) or other toxicities not considered a safety risk to the patient.
10. Adequate organ function as defined by the following criteria:
· 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 (Patients with Gilbert's disease with total bilirubin less than/ equal to 2.5 x ULN)
· Absolute neutrophil count (ANC) ≥ 1500/microL
· Platelets ≥ 100,000/microL
· Hemoglobin ≥8.5 g/dL
· Calculated creatinine clearance > 50 ml/min
· Serum albumin ≥2.5 g/dL
· Serum creatinine less than or equal to 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.
|
|
| E.4 | Principal exclusion criteria |
1. More than 2 prior regimens of chemotherapy in the advanced/metastatic disease
setting and any prior regimen containing capecitabine.
2. Major surgery, radiation therapy, or systemic therapy (except hormone 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.
3. Wounds that have not completely healed, active ulcer(s), or bone fracture(s).
4. Current treatment on another clinical trial.
5. Brain metastases, spinal cord compression, or carcinomatous meningitis, or
leptomeningeal disease.
6. Bone lesions as the only manifestation of current metastatic breast cancer.
7. Diagnosis of any second malignancy within the last 3 years, except for previous breast cancer,adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
8. 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.
9. Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2 or QTc interval >470 msec for females.
10. Hypertension that cannot be controlled by medications (>150/100 mmHg
despite optimal medical therapy).
11. 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). If currently receiving treatment with these agents, patients must have their PT or INR monitored. Low molecular weight heparin is allowed at any dose level.
12. Known human immunodeficiency virus infection as well as patients with active Hepatitis B and C infection. Active infection is defined as patients requiring treatment.
13. 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 period of study and for 90 days after last dose of study treatment. All female patients with reproductive potential
must have a negative pregnancy test (serum or urine) prior to first day of study
medication.
14. 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.
15. History of severe and unexpected reactions to fluoropyrimidine therapy or
known hypersensitivity to 5-fluorouracil or capecitabine or any excipients of
capecitabine.
16. Known dihydropyrimidine dehydrogenase deficiency.
17. Current treatment with sorivudine or its chemically related analogues, such as
brivudine.
18. Prior treatment with anti-angiogenic therapy including
multitargeted TKIs such as sorafenib or experimental agents.Prior treatment with bevacizumab will be permitted.
19. Pre-existing thyroid abnormality with thyroid function that cannot be maintained
in the normal range.
20. Prior treatment with TS-1 (tegafur/gimeracil/oteracil) |
|
| 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 | 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 | 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 | 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 | 14 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| 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 years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
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