Pilot / Phase II Randomised, Double Blind, Placebo Controlled Multicenter Study With Biomarker Evaluation of Neoadjuvant Exemestane in Combination With Sunitinib in Post-menopausal Women With Hormone- Sensitive, Her-2 Negative Primary Breast Cancer.
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.
Interventional
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Treatment
Recommended dose of sunitinib malate that can be combined with exemestane
Yes
Sonia Pernas, MD
Institut Catala D'Oncologia
Unspecified
CDR0000640330
NCT00931450
March 2009
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