Finding studies
Finding studies
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Lead
Institut Català d'Oncologia
OBJECTIVES: Primary * Determine the safe dose level of sunitinib malate that can be combined with exemestane (pilot phase I). * Evaluate the clinical response of neoadjuvant therapy comprising exemestane and sunitinib malate in postmenopausal women with hormone receptor-positive and HER-2 negative primary breast cancer (phase II). Secondary * Evaluate the safety and feasibility of this regimen in these patients. * Evaluate the percentage of patients undergoing breast-conserving surgery after completion of study therapy. * Determine the safety profile of this regimen in these patients. * Determine the rate of complete pathological response in the breast and axillary lymph nodes at the time of surgery. * Determine the extent of treatment-related inhibition of phosphorylation of VEGFR-2, PDGF, and c-KIT receptor tyrosine kinases. * Find a genetic profile, based on the analysis of CYP19A1 polymorphisms, able to predict response to exemestane in neoadjuvant setting. * Conduct exploratory investigation of biomarkers expression before and during therapy in order to identify molecular characteristics of responding tumors. OUTLINE: This is a multicenter, dose-escalation study of sunitinib malate followed by a phase II study. * Phase I pilot: Patients receive oral sunitinib malate and oral exemestane once daily on days 1-28. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. * Phase II: Patients are randomized to 1 of 2 treatment groups: * Group 1: Patients receive oral exemestane and oral placebo once daily on days 1-28. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. * Group 2: Patients receive oral exemestane once daily and oral sunitinib malate once daily on days 1-28. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. At 7-15 days after completion of study therapy, patients undergo definitive surgery. Blood and tissue samples are collected at baseline and periodically during study to examine inhibition of phosphorylation of VEGFR-2, PDGF, and c-KIT receptor tyrosine kinases; CYP19A1 polymorphisms; and biomarkers analysis by cDNA microarrays, ELISA, and RT-PCR.
Age
Any age
Sex
FEMALE
Healthy volunteers
Not accepted
