Phase III Randomized, Multi Center Study of Sunitinib Malate (SU 011248) or Capecitabine in Subjects with Advanced Breast Cancer who failed both a taxane and an anthracycline chemotherapy regimen or failed with a taxane and for whom further anthracycline therapy is not indicated - Amendment #7
- Conditions
- Histologically or cytologically proven diagnosis of breast adenocarcinoma that is not amenable to surgery, radiation, or combined modality therapy with curative intentMedDRA version: 9.1Level: LLTClassification code 10006203Term: Breast cancer stage unspecified
- Registration Number
- EUCTR2006-001267-33-GB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 700
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the trial:
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 or 1+ or FISH negative. CISH can replace either test where approved; if more than one test was done, the results 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 the 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 =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) =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 with a total serum bilirubin =2.5 x ULN)
• Absolute neutrophil count (ANC) =1500/µL
• Platelets =100,000/µL
• Hemoglobin =8.5 g/dL
• Calculated creatinine clearance > 50 ml/min.
• Serum albumin =2.5 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Patients presenting with any of the following will not be included in the trial:
1. More than 2 prior regimens of chemotherapy in the advanced/metastatic disease setting and any prior regimen containing capecitabine.
2. Major surgery 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 a 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 accidentincluding 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 the 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 multi-targeted 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)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method