Clinical trial NCT01081613: Imaging HSP90 Inhibitor AUY922 on VEGF-89ZR-bevacizumab Positron Emission Tomography (PET)
Official title: Imaging the Effect of HSP90 Inhibitor AUY922 on VEGF by Means of 89Zr-bevacizumab PET
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Cancer
Keywords: heat shock protein
breast cancer
PET imaging
bevacizumab
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 ER positive, hormone therapy refractory breast cancer, who are participating in the phase I-II trial with HSP90 inhibitor AUY922

Brief summary: Inhibition of Heat Shock Protein (HSP)90 is a new, promising treatment modality for cancer patients, particularly in the setting of resistance. A reliable read out system (biomarker) for the evaluation of early treatment effect is of great importance in the development of this treatment modality, and could contribute to customize this treatment for individual patients. So far, no reliable biomarker has been described for HSP90 effect. Visualizing the effect of HSP90 on vascular endothelial growth factor (VEGF) secretion in vivo in the patient, by whole body 89Zr-bevacizumab uptake, can be of great importance in this respect, and may contribute to tailored made cancer treatment. The purpose of the present study is to evaluate the effect of HSP90 inhibition by AUY922 on VEGF by means of 89ZR-bevacizumab PET.

Detailed description: This feasibility study is designed as a side study to the multicenter, international phase I-II trial with 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 (p37, 38). Briefly, a dose-escalation study is performed according to phase I design in adult patients with advanced solid malignancies. 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), on the maximal tolerated dose of AUY922 based on the phase I part of the study. Patients with ER positive, hormone therapy refractory breast cancer, will receive a 89Zr-bevacizumab 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-bevacizumab PET scan will be performed before (baseline) and during treatment with HSP90 inhibitor AUY922, as described below.

A minimum of six patients will be entered to evaluate whether the effect of HSP90 inhibition by AUY922 can be detected with a 89Zr-bevacizumab PET scan

Eligibility criteria: Inclusion Criteria:

* patients with ER positive, hormone therapy refractory breast cancer
* participation in the phase I-II trial with HSP90 inhibitor AUY922 (in- and exclusion criteria for the study with AUY922 are described in protocol CAUY922A2101, Clinical Trials no NCT00526045A.

Exclusion Criteria:

* no participation in the phase I-II trial with HSP90 inhibitor AUY922

Primary outcomes:
measure: To evaluate the effect of HSP90 inhibition by AUY922 on VEGF by means of 89Zr-bevacizumab PET.
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: