HER2 Imaging Study to Identify HER2 Positive Metastatic Breast Cancer Patient Unlikely to Benefit From T-DM1 (ZEPHIR)
|ClinicalTrials.gov Identifier: NCT01565200|
Recruitment Status : Active, not recruiting
First Posted : March 28, 2012
Last Update Posted : November 29, 2017
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
|Condition or disease||Intervention/treatment||Phase|
|HER-2 Positive Breast Cancer||Drug: T-DM1 Procedure: 89Zr-trastuzumab||Phase 2|
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 (Clinical Trial)|
|Actual Enrollment :||90 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||May 2012|
|Estimated Primary Completion Date :||June 2018|
|Estimated Study Completion Date :||December 2018|
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
- negative predictive value of the 89Zr-trastuzumab PET/CT [ Time Frame: 2 years ]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).
- negative predictive value of the early FDG PET/CT [ Time Frame: 2 years ]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.
- negative predictive value of the 89Zr-trastuzumab PET/CT [ Time Frame: 2 years ]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.
- negative predictive value of the combined 89Zr-trastuzumab PET/CT and early PET/CT [ Time Frame: 2 years ]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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01565200
|Universitair Ziekenhuis Antwerpen (UZA)|
|Antwerpen, Edegem, Belgium, 2650|
|Institut Jules Bordet|
|Brussels, Belgium, 1000|
|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:||Patrick Flamen, MD/PhD||Jules Bordet Institute|