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

NCT ID: NCT01081600

Last Updated: 2013-05-14

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 7 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2010-02-28
• Study Completion Date: 2012-02-29

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.

Conditions

Breast Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

AUY922

Patients with HER2 positive breast cancer which has become trastuzumab resistent.

Imaging with 89Zr-trastuzumab PET

Intervention Type: OTHER

Injection with 89Zr-trastuzumab and 89Zr-trastuzumab PET scan.

Interventions

Imaging with 89Zr-trastuzumab PET

Injection with 89Zr-trastuzumab and 89Zr-trastuzumab PET scan.

Intervention Type: OTHER

Other Intervention Names

89Zr-trastuzumab

Eligibility Criteria

Inclusion Criteria

• Patients with HER2 positive, trastuzumab (and lapatinib) refractory breast cancer

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

C.P. Schroder

Principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

C.P. Schröder, PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Locations

University Medical Center Groningen

Groningen, Provincie Groningen, Netherlands

Countries

Netherlands

Other Identifiers

2008-005751-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

27112008 version 1

Identifier Type: -

Identifier Source: org_study_id