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HER-2 Positive Breast CancerPhase 2ZEPHIRNCT01565200

HER2 Imaging Study to Identify HER2 Positive Metastatic Breast Cancer Patient Unlikely to Benefit From T-DM1

A Phase 2 study testing T-DM1 and 89Zr-trastuzumab in people with HER-2 Positive Breast Cancer, run by Jules Bordet Institute at 5 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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%… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HER-2 Positive Breast Cancer
What is being tested?
T-DM1 and 89Zr-trastuzumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
90 participants
Where
5 sitesin 2 countries
Study dates
May 2012to Dec 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The patient must have histologically confirmed HER2 positive invasive carcinoma of the breast in the reference laboratory of the participating center. HER2 positive criteria to be applied are those used in the participating countries:
  • Belgium: FISH amplification ratio ≥ 2 in the reference laboratory of the participating center
  • The Netherlands: IHC 3+ or FISH ratio ≥ 2 in the reference laboratory of the participating center
  • The patient must have documented progressive disease and present with at least 2 non-bone "target" metastatic lesions, unequivocally of neoplastic origin with
  • a transaxial diameter greater than 2 cm on the screening diagnostic CT/MRI for all non-bone lesions except lymphnodes
  • a short axis greater than 1,5 cm for lymphnodes on the screening diagnostic CT/MRI These two lesions should not be confluent with adjacent lesions and not have been irradiated previously.
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  • A concurrent biopsy of a metastatic site is mandatory (with two formalin fixed paraffin embedded (FFPE) core sample and two snap frozen tumor sample) after progression has been documented and before inclusion and the patient agrees with the procedure.
  • Primary tumor blocks (or 11 unstained slides) available for confirmatory central laboratory HER2 testing in Institut Jules Bordet. If available, a snap frozen sample of the primary tumor will also be centralized in Institut Jules Bordet.
  • Age ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1
  • No significant cardiac history and current LVEF ≥ 50%
  • Adequate organ function, evidenced by the following laboratory results:
  • Absolute neutrophil count > 1,500 cells/mm3
  • Platelet count > 100,000 cells/mm3
  • Hemoglobin > 9 g/dL
  • AST(SGOT) and ALT (SGPT) < 2.5 x ULN
  • Total Bilirubin ≤ 1.5 x ULN unless the patient has documented Gilbert's syndrome. Patients with known Gilbert's Syndrome should have direct bilirubin within normal limits.
  • Serum alkaline phosphatase ≤ 2.5 x ULN. Patients with bone metastases: alkaline phosphatase ≤ 5 x ULN
  • Serum creatinine < 2.0 mg/dL or 177 μmol/L
  • International normalized ratio (INR) and activated partial thromboplastin time or partial thromboplastin time (aPTT or PTT) < 1.5 x ULN (unless on therapeutic anti-coagulation except vitamin K antagonists which are prohibited in this study)
  • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
  • For women of childbearing potential a serum pregnancy test will be done (and it must be negative) and an agreement to use a highly-effective form of contraception during all the study and at least the following 7 months will be obtained.
  • Signed written informed consent obtained prior to any study specific procedure.
  • Completion of all necessary baseline surgical, laboratory and imaging investigations prior to patient inclusion.

Who cannot join

  • Patients with bone only metastases are not eligible.
  • Diffuse liver (≥50%) involvement on imaging.
  • Patients with brain metastasis as the sole site of metastatic disease and/or are symptomatic or require therapy to control symptoms NB: Brain metastasis are allowed provided they are asymptomatic and/or controlled by previous radiotherapy. In case of recent prior brain radiotherapy, there must be evidence on MRI imaging of brain metastatic control for at least 6 weeks since the end of radiotherapy. Moreover, the patient should be at the end of corticosteroid therapy and be clinically asymptomatic.
  • Current uncontrolled hypertension despite medication intake (systolic > 150 mmHg and/or diastolic > 100 mmHg)
  • Current unstable angina
  • History of symptomatic CHF of any New York Heart Association (NYHA) criteria or ventricular arrhythmia that requires treatment
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  • History of myocardial infarction within the last 6 months
  • History of a decrease in LVEF to < 40% or symptomatic CHF with previous trastuzumab treatment
  • Current dyspnea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy
  • Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures)
  • History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other cancers with a similar outcome as those previously mentioned
  • Pregnant or lactating women
  • Concurrent, serious, uncontrolled infections or current known infection with HIV, active hepatitis B and/or hepatitis C.
  • Known prior severe hypersensitivity to trastuzumab
  • Patient who received lapatinib within the 15 days prior to 89Zr-Trastuzumab injection
  • Patient under a prohibited concomitant therapy, including vitamine K antagonist
  • Patients with a peripheral neuropathy Grade 3 or higher

Trial locations and contacts

5 sites in 2 countries.

5 sites in 2 countries

Netherlands3 sites

  • Vrije Universiteit Amsterdam (VUMC)

    Amsterdam, 1081HV

  • University Medical Center Groningen (UMCG)

    Groningen, 9700RB

  • Radboud University Medical Centre Nijmegen (UMCN)

    Nijmegen, 6525 GA

Other trials in Netherlands

Belgium2 sites

  • Universitair Ziekenhuis Antwerpen (UZA)

    Antwerp, Edegem, 2650

  • Institut Jules Bordet

    Brussels, 1000

Other trials in Belgium

About this study

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

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.

Read more

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

Read the detailed description

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.

Being tested
T-DM1, 89Zr-trastuzumab
Keywords
HER2, Metastatic Breast Cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • T-DM1Drug

    Also called Trastuzumab-DM1

    3.6 mg/kg iv every 3 weeks

  • 89Zr-trastuzumabProcedure or surgery

    Also called Zirconium 89 labelled trastuzumab

    Injection of 89Zr-trastuzumab for HER2 imaging

Study groups in NCT01565200
Study groupRoleWhat they receive
T-DM1OtherAfter an imaging phase, the patient will receive T-DM1 iv every 3 weeks until progression or toxicity
Receives: Drug: T-DM1; Procedure: 89Zr-trastuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: 2 years

Secondary outcomes (3)

  1. 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.

    Measured: 2 years

  2. 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.

    Measured: 2 years

  3. 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.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Mar 2012 (estimated)
  2. Study startMay 2012
  3. Primary completionJul 2017
  4. Study completionDec 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Diagnosis
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
90 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01565200
Sponsor's protocol ID
IJBMNTDM1
Other IDs
2011-005437-39
Acronym
ZEPHIR
Status last verified
Nov 2022
First submitted
22 Mar 2012
Last updated
31 Mar 2025
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Gebhart G, Lamberts LE, Wimana Z, Garcia C, Emonts P, Ameye L, Stroobants S, Huizing M, Aftimos P, Tol J, Oyen WJ, Vugts DJ, Hoekstra OS, Schroder CP, Menke-van der Houven van Oordt CW, Guiot T, Brouwers AH, Awada A, de Vries EG, Flamen P. Molecular imaging as a tool to investigate heterogeneity of advanced HER2-positive breast cancer and to predict patient outcome under trastuzumab emtansine (T-DM1): the ZEPHIR trial. Ann Oncol. 2016 Apr;27(4):619-24. doi: 10.1093/annonc/mdv577. Epub 2015 Nov 23.

    PubMed 26598545

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing T-DM1 and 89Zr-trastuzumab in people with HER-2 Positive Breast Cancer, run by Jules Bordet Institute at 5 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Netherlands, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

negative predictive value of the 89Zr-trastuzumab PET/CT (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01565200, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2025.

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