89Zr-trastuzumab PET for Imaging the Effect of HSP90 Inhibition

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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT01081600

Acronym

AUY922

Enrollment

Registered

2010-03-05

Start date

2010-02-28

Completion date

2012-02-29

Last updated

2013-05-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Cancer

Keywords

Heat shock protein, breast cancer, PET imaging, trastuzumab

Brief summary

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.

Detailed description

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.

Interventions

OTHERImaging with 89Zr-trastuzumab PET

Injection with 89Zr-trastuzumab and 89Zr-trastuzumab PET scan.

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Patients with HER2 positive, trastuzumab (and lapatinib) refractory breast cancer * Participation in the phase I-II trial with HSP90 inhibitor AUY922 (in- and

Exclusion criteria

for this study with AUY922 are described in protocol CAUY922A2101.

Design outcomes

Primary

Measure	Time frame	Description
To show the effect of the HSP90 inhibitor AUY922 on HER2 expression by means of 89Zr-trastuzumab PET scanning.	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.

Countries

Netherlands

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026