Clinical trial NCT01081600: 89Zr-trastuzumab PET for Imaging the Effect of HSP90 Inhibition
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 type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Cancer
Keywords: Heat shock protein
breast cancer
PET imaging
trastuzumab
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2010-03-05
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with HER2 positive breast cancer which has become trastuzumab resistent, who are participating in the phase I-II trial with HSP90 inhibitor AUY922

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.

Eligibility criteria: 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)

Primary outcomes:
measure: To show the effect of the HSP90 inhibitor AUY922 on HER2 expression by means of 89Zr-trastuzumab PET scanning.
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: C.P. Schröder, PhD
role: PRINCIPAL_INVESTIGATOR
References: