89Zr-trastuzumab PET for Imaging the Effect of HSP90 Inhibition (AUY922)
|ClinicalTrials.gov Identifier: NCT01081600|
Recruitment Status : Completed
First Posted : March 5, 2010
Last Update Posted : May 14, 2013
HSP90 inhibition is a potentially new targeted drug modality in the treatment of HER2 positive, trastuzumab refractory breast cancer. Little is known about the pharmacodynamics of HSP90 inhibitors in vivo, but non-invasive PET/CT imaging in a xenograft mouse model could visualize and quantify HER2 reduction after AUY922 treatment by 89Zr-trastuzumab PET imaging. Two doses of 50 mg/kg AUY922 resulted in a decrease in HER2 expression of approximately 50%, quantified 6 days after the last administration of AUY922.
Visualizing HER2 expression in breast cancer patients before and early following HSP90 inhibition by means of 89Zr-trastuzumab PET, is likely to provide insight in the early in vivo effect of HSP90 inhibition and could potentially support patient tailored therapy.
|Condition or disease||Intervention/treatment|
|Breast Cancer||Other: Imaging with 89Zr-trastuzumab PET|
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.
|Study Type :||Observational|
|Actual Enrollment :||7 participants|
|Official Title:||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|
|Study Start Date :||February 2010|
|Primary Completion Date :||February 2012|
|Study Completion Date :||February 2012|
Patients with HER2 positive breast cancer which has become trastuzumab resistent.
Other: Imaging with 89Zr-trastuzumab PET
Injection with 89Zr-trastuzumab and 89Zr-trastuzumab PET scan.
Other Name: 89Zr-trastuzumab
- To show the effect of the HSP90 inhibitor AUY922 on HER2 expression by means of 89Zr-trastuzumab PET scanning. [ Time Frame: 2 years ]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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01081600
|University Medical Center Groningen|
|Groningen, Netherlands, 9713 GZ|
|Principal Investigator:||C.P. Schröder, PhD||University Medical Center Groningen|