89Zr-trastuzumab PET for Imaging the Effect of HSP90 Inhibition (AUY922)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
C.P. Schroder, University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT01081600
First received: March 4, 2010
Last updated: May 13, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention
Breast Cancer
Other: Imaging with 89Zr-trastuzumab PET

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
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

Resource links provided by NLM:


Further study details as provided by University Medical Centre Groningen:

Primary Outcome Measures:
  • To show the effect of the HSP90 inhibitor AUY922 on HER2 expression by means of 89Zr-trastuzumab PET scanning. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 7
Study Start Date: February 2010
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
AUY922
Patients with HER2 positive breast cancer which has become trastuzumab resistent.
Other: Imaging with 89Zr-trastuzumab PET
Injection with 89Zr-trastuzumab and 89Zr-trastuzumab PET scan.
Other Name: 89Zr-trastuzumab

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01081600

Locations
Netherlands
University Medical Center Groningen
Groningen, Netherlands, 9713 GZ
Sponsors and Collaborators
University Medical Centre Groningen
Investigators
Principal Investigator: C.P. Schröder, PhD University Medical Centre Groningen
  More Information

No publications provided

Responsible Party: C.P. Schroder, Principal investigator, University Medical Centre Groningen
ClinicalTrials.gov Identifier: NCT01081600     History of Changes
Other Study ID Numbers: 27112008 version 1, 2008-005751-26
Study First Received: March 4, 2010
Last Updated: May 13, 2013
Health Authority: Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by University Medical Centre Groningen:
Heat shock protein
breast cancer
PET imaging
trastuzumab

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 16, 2014