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

Completed

• Conditions: Breast Cancer
• Interventions: Other: Imaging with 89Zr-trastuzumab PET

• Registration Number: NCT01081600
• Lead Sponsor: University Medical Center Groningen

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.

Study Timeline

• Study Start: 2010-02
• Study First Submitted: 2010-03-04
• Study First Submitted QC: 2010-03-04
• Study First Posted: 2010-03-05
• Primary Completion: 2012-02
• Study Completion: 2012-02
• Status Verified: 2013-05
• Last Update Submitted: 2013-05-13
• Last Update Posted: 2013-05-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 7

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.

Exclusion Criteria

• No participation in the phase I-II trial with HSP90 inhibitor AUY922 (CAUY922A2101. Clinical trials no. NCT00526045A)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
AUY922	Imaging with 89Zr-trastuzumab PET	Patients with HER2 positive breast cancer which has become trastuzumab resistent.

Primary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

University Medical Center Groningen; 🇳🇱 Groningen, Netherlands