Imaging the Effect of HSP90 Inhibitor AUY922 on HER2 Expression by Means of 89Zr-trastuzumab PET. Side Study to Phase I-II Study With AUY922 in Either HER2 or ER Positive Locally Advanced or Metastatic Breast Cancer: Protocol CAUY922A2101
This study is designed as a side study to the multicenter, international phase I-II trial
with the HSP90 inhibitor AUY922 (protocol CAUY922A2101), as part of the biomarker
assessment. In protocol CAUY922A2101, section 4, the design of this phase I-II trial is
described (p36, 37). Briefly, a dose-escalation study is performed according to phase I
design. This part is followed by a dose-expansion study according to a phase II design. In
the latter part, breast cancer patients are enrolled that are either refractory to hormone-
or trastuzumab treatment (both treatment arms, n=40 patients). Patients with HER2 positive,
trastuzumab refractory breast cancer, will receive a 89Zr-trastuzumab PET scan as part of
the present side study protocol, which will be performed in collaboration with the Royal
Marsden Hospital (United Kingdom).
To this end, a 89Zr-trastuzumab PET scan will be performed before (baseline) and during
treatment with the HSP90 inhibitor AUY922, as described below.
A minimum of six patients are needed to evaluate whether the 89Zr-trastuzumab PET scan can
be used for the detection of a decrease of HER2 expression, induced by HSP90 inhibition.
Observational Model: Cohort, Time Perspective: Prospective
To show the effect of the HSP90 inhibitor AUY922 on HER2 expression by means of 89Zr-trastuzumab PET scanning.
Primary endpoint: measurement of decreased HER2 expression compared to baseline. A decline is defined as a decrease of at least 30% in mean Standardized Uptake Value (SUV) in a maximum of three lesions.
C.P. Schröder, PhD
University Medical Centre Groningen
Netherlands: Medical Ethics Review Committee (METC)
27112008 version 1