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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Breast Cancer

Intervention / Treatment
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* Other: Imaging with 89Zr-trastuzumab PET


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| AUY922<br>Patients with HER2 positive breast cancer which has become trastuzumab resistent. | Other: Imaging with 89Zr-trastuzumab PET<br>* Injection with 89Zr-trastuzumab and 89Zr-trastuzumab PET scan.<br>* Other names: 89Zr-trastuzumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heat shock protein, breast cancer, PET imaging, trastuzumab