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
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
90
3.6 mg/kg iv every 3 weeks
Injection of 89Zr-trastuzumab for HER2 imaging
Universitair Ziekenhuis Antwerpen (UZA)
Antwerp, Edegem, Belgium
Institut Jules Bordet
Brussels, Belgium
Vrije Universiteit Amsterdam (VUMC)
Amsterdam, Netherlands
University Medical Center Groningen (UMCG)
Groningen, Netherlands
Radboud University Medical Centre Nijmegen (UMCN)
Nijmegen, Netherlands
negative predictive value of the 89Zr-trastuzumab PET/CT
The primary objective is to show that pre-treatment 89Zr-trastuzumab PET/CT is able to select lesions not responding morphologically from treatment with T-DM1 (applying RECIST 1.0 criteria).
Time frame: 2 years
negative predictive value of the early FDG PET/CT
The first secondary objective is to show that early FDG PET/CT (performed after one cycle of T-DM1 just before the second cycle) is able to select lesions not responding from treatment with T-DM1 according to metabolic and morphological response criteria post 3 cycles of T-DM1.
Time frame: 2 years
negative predictive value of the 89Zr-trastuzumab PET/CT
The second secondary objective is to show that 89Zr-trastuzumab PET/CT is able to select lesions not responding from treatment with T-DM1 according to metabolic response criteria post 3 cycles of T-DM1.
Time frame: 2 years
negative predictive value of the combined 89Zr-trastuzumab PET/CT and early PET/CT
The third secondary objective is to show that a lesion with no/faint uptake on 89Zr-trastuzumab PET/CT and not responding metabolically on the early FDG-PET/CT will not respond according to metabolic and morphological criteria after 3 cycles of T-DM1.
Time frame: 2 years
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