large operable and locally advanced breast cancer MedDRA version: 9.1 Level: LLT Classification code 10006187 Term: Breast cancer
Conditions
Sponsors
IPOLFG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically or cytologically proven newly diagnosed untreated invasive breast cancer (independent of ER, PgR and Her2 status), existence of a tumour greater than 3 cm in diameter by caliper measurement and/or N2-3 disease with a palpable breast mass. 2. Indication for neoadjuvant chemotherapy as judged by the institutional multidisciplinary conference (large operable tumour aiming at breast conservation, locally advanced or inflammatory disease). 3. Multifocal and multicentric breast tumours are allowed as long as only two tumour foci are identified, since two sequential tumour samples are to be collected from each tumour focus. 4. Consent to perform two core biopsies: one immediately before sunitinib administration and another after the two weeks of the first course of sunitinib treatment. 5. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. 6. Adequate organ function 7. Female, 18 years of age or older. 8. ECOG performance status 0, 1 or 2. 10. 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 enrolment. 11. Consent to undergo breast cancer surgery at day 113. 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
Exclusion criteria
Exclusion criteria: 1. 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. 2. Prior treatment for cancer, including systemic chemo or endocrine therapy, surgery or radiation, tyrosine kinase inhibitors or antiangiogenic therapy. 3. Metastatic breast cancer. 4. Patients for whom docetaxel is contraindicated according to the local prescribing information. 5. History of severe hypersensitivity reactions to docetaxel or to other drugs formulated with polysorbate 80. 6. Major surgery, radiation therapy, or systemic therapy within 3 weeks of start of study treatment. 7. Prior radiation therapy to >25% of the bone marrow (whole pelvis is 25%). 8. Current treatment on another clinical trial. 9. 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. 10. Ongoing cardiac dysrhythmias of grade =2, atrial fibrillation of any grade, or QTc interval >470 msec. 11. Hypertension that cannot be controlled by medications (>150/100 mmHg) despite optimal medical therapy). 12. Current treatment with therapeutic doses of warfarin (low dose warfarin up to 2 mg PO daily for deep vein thrombosis prophylaxis or i.v. catheter patency is allowed). 13. Known human immunodeficiency virus infection. 14. Pregnancy or breastfeeding. 15. Female of child-bearing potential that is unwilling or unable to use adequate contraception to prevent pregnancy during the program, (all female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to study entry). 16. Other severe acute, chronic medical, 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: Assessment of efficacy of sunitinib and docetaxel as neoadjuvant treatment for large operableand locally advanced breast cancer;Secondary Objective: Safety and tolerability profile of the association of sunitinib and docetaxel Assessment of pharmacodynamic activity of sunitinib and docetaxel Assessment of sunitinib’s antitumour effect Assessment of sunitinib’s biologic activity;Primary end point(s): Primary Pathologic complete response (pCR) rate. Secondary i. Clinical Endpoints Overall safety profile characterized by type, incidence, severity, timing, seriousness, and relationship to study therapy of adverse events; laboratory abnormalities. ii. Pharmacodynamic activity Change between time point 2 (day 15, after sunitinib alone) and time point 1 (baseline) and between time point 3 (surgery) and time point 2 in: 1. Proliferation marker: Ki67 2. Anti-angiogenic effects 3. Apoptosis of tumour cells: TUNNEL 4. Chemotaxis Axis: CXCR4 and CXCL12/SDF1 ii. Gene signature of sunitinib antitumour effect: Collection of fresh tissue on time points 1 and 2 for identification of a gene array profile associated with the biologic effects of sunitinib. iii. Surrogate Imaging Endpoints of Biologic Activity: Comparison of tumour vascularization, by Gad-enhanced breast MRI, and tumour cell metabolism, by FDG-PET, between time points 2 and 1. | — |
Countries
Portugal
Outcome results
None listed