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. Tumors over-expressing Her-2 (3+ by immunohistochemistry [IHC] or FISH-positive). MedDRA version: 9.1 Level: LLT Classification code 10006202 Term: Breast cancer stage IV
Conditions
Interventions
Trade Name: Sutent
Product Name: sunitinib malate
Product Code: SU011248
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Sunitinib Malate
Current Sponsor code: SU-011248
Concentration unit: mg
Sponsors
Pfizer Global Research & Development, La Jolla Laboratories
Eligibility
Sex/Gender
All
Inclusion criteria
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. Tumors over-expressing Her-2 (3+ by immunohistochemistry [IHC] or FISH-positive). 3. Measurable disease as per RECIST. Presence of at least 1 measurable lesion not previously irradiated. 4. Candidate for treatment with trastuzumab and docetaxel. 5. May have received: • Prior adjuvant or neo-adjuvant chemotherapy. • If adjuvant therapy included trastuzumab, relapse must have occurred =6 months since last dose of trastuzumab. • If adjuvant therapy included a taxane, relapse must have occurred =12 months since last dose of chemotherapy. • Hormonal therapy concurrent or sequential to adjuvant chemotherapy is allowed. • Hormonal therapy for advanced disease is allowed but is to be discontinued =3 weeks prior to study treatment. • Not allowed a prior treatment with chemotherapy in the advanced disease setting. 6. May have received prior radiation therapy. A measurable lesion that has been previously irradiated will not be considered a target lesion and will be evaluated only when it increases in size. Radiotherapy is to be completed =3 weeks prior to study treatment, except in the case of palliative radiotherapy for bone lesions. 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). 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 • Alkaline phosphatase (ALP) =2.5 x ULN • Total serum bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Histology of inflammatory carcinoma. 2. Prior treatment on a SU011248 clinical trial. 3. Prior treatment with any tyrosine kinase inhibitors, VEGF inhibitors, or other angiogenic inhibitors. 4. History of severe hypersensitivity reactions to docetaxel or to other drugs formulated with polysorbate 80. 5. History of severe hypersensitivity reactions to trastuzumab. 6. AST and/or ALT >1.5 x ULN concomitant with ALP >2.5 x ULN. 7. Major surgery, radiation therapy, or systemic therapy within 3 weeks of study registration. At least 1 week should elapse since minor surgical procedure including placement of an access device or fine needle aspiration. 8. Prior high-dose chemotherapy requiring hematopoietic stem cell rescue. 9. Prior radiation therapy to >25% of the bone marrow (whole pelvis is 25%). 10. Current treatment on another clinical trial. 11. Known brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease. However, patients who have had brain metastases surgically removed can be included. 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 12 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischemic attack, or pulmonary embolus. 14. Ongoing cardiac dysrhythmias of grade =2, atrial fibrillation of any grade, 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 Coumadin (low dose Coumadin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed). 17. Known human immunodeficiency virus infection. 18. Pregnancy or breastfeeding. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to randomization. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the tolerability of the combination of SU011248 (37.5 mg once daily [Schedule 2/1]) with docetaxel (75 mg/m2 every 3 weeks) and trastuzumab (therapeutic dose) in patients with advanced breast cancer over-expressing Her-2.;Secondary Objective: To assess preliminary anti-tumor activity of the combination. To determine trough plasma concentrations (Ctrough) of SU011248 and its active metabolite SU012662, plasma concentrations of paclitaxel and serum concentrations of trastuzumab.;Primary end point(s): Safety profile characterized by type, incidence, severity, timing, seriousness, and relatedness of adverse events; and laboratory abnormalities | — |
Countries
Belgium, Italy
Outcome results
None listed