HER2 Imaging Study to Identify HER2 Positive Metastatic Breast Cancer Patient Unlikely to Benefit From T-DM1 (ZEPHIR)
T-DM1 , which is a highly innovative but also expensive antiHER2 agent consisting in the coupling of the humanised monoclonal antibody trastuzumab with a cytotoxic agent (maytansine derivate) has shown an encouraging antitumor activity evaluated by Recist criteria (35% objective response rate, 44% stable disease, 18% progressive disease) in patients with advanced HER2 positive Breast Cancer pretreated with several cytotoxic drugs, trastuzumab and lapatinib.
Rationale I :For TDM1 to be active, the presence of an intact HER2 receptor is "key" since the internalization of the cytotoxic moiety depends on the binding of trastuzumab to the external domain of HER2.
The zirconium 89 labelled trastuzumab PET/CT (or HER2 immunoPET/CT) is a non invasive test which shows promise in measuring HER2 expression (extracellular domain) for the entire disease burden and which could identify non responding patients prior to TDM1 administration.
Rationale II: As for many such agents, it is desirable to identify early on (here with the use of FDG-PET/CT) which patients are unlikely to benefit from the therapy
HER-2 Positive Breast Cancer
|Study Design:||Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||Phase II Prospective Imaging Study Evaluating the Utility of Pre-treatment zr89 Labelled Trastuzumab PET/CT and an Early FDG-PET/CT Response to Identify Patients With Advanced HER2+ BC Unlikely to Benefit From a Novel antiHER2 Therapy: TDM1|
- negative predictive value (NPV) of the 89Zr-trastuzumab PET/CT [ Time Frame: 2 years ] [ Designated as safety issue: No ]The primary objective is to show that pre-treatment 89Zr-trastuzumab PET/CT is able to select lesions not responding from treatment with T-DM1 according to the RECIST 1.1
- negative predictive value of the early FDG PET/CT [ Time Frame: 2 years ] [ Designated as safety issue: No ]The secondary objective is to show that early FDG PET/CT (performed after one cycle of T-DM1) is able to select lesions not responding from treatment with T-DM1 according to RECIST 1.1.
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||April 2015|
|Estimated Primary Completion Date:||April 2015 (Final data collection date for primary outcome measure)|
After an imaging phase, the patient will receive T-DM1 iv every 3 weeks until progression or toxicity
3.6 mg/kg iv every 3 weeks
Other Name: Trastuzumab-DM1Procedure: 89Zr-trastuzumab
Injection of 89Zr-trastuzumab for HER2 imaging
Other Name: Zirconium 89 labelled trastuzumab
The main objective of the trial is to prospectively evaluate the ability of a zirconium 89 labelled trastuzumab PET, to predict, before initiation of the treatment, treatment failure to a new targeted drug: T-DM1.
At the same time, the early FDG-PET/CT, performed after 1 course of T-DM1, will also evaluated for its ability to predict non response to TDM1.
|Universitair Ziekenhuis Antwerpen (UZA)|
|Antwerpen, Edegem, Belgium, 2650|
|Institut Jules Bordet|
|Brussels, Belgium, 1180|
|Vrije Universiteit Amsterdam (VUMC)|
|Amsterdam, Netherlands, 1081HV|
|University Medical Center Groningen (UMCG)|
|Groningen, Netherlands, 9700RB|
|Radboud University Medical Centre Nijmegen (UMCN)|
|Nijmegen, Netherlands, 6525 GA|
|Study Chair:||Geraldine Gebhart, MD||Jules Bordet Institute|