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

NCT01565200 | Completed Phase 2

• 2 other identifiers: IJBMNTDM12011-005437-39
• Study Type: interventional
• Target: 90
• Locations: 2 countries
• Sites: 5

Brief 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% 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

Conditions

HER-2 Positive Breast Cancer

Keywords

HER2; Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (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).

  2 years

Secondary Outcomes (3)

• negative predictive value of the early FDG PET/CT

  2 years

• negative predictive value of the 89Zr-trastuzumab PET/CT

  2 years

• negative predictive value of the combined 89Zr-trastuzumab PET/CT and early PET/CT

  2 years

Study Arms (1)

T-DM1

OTHER

After an imaging phase, the patient will receive T-DM1 iv every 3 weeks until progression or toxicity

Drug: T-DM1; Procedure: 89Zr-trastuzumab

Interventions

T-DM1 DRUG

3.6 mg/kg iv every 3 weeks

Also known as: Trastuzumab-DM1

T-DM1

89Zr-trastuzumab PROCEDURE

Injection of 89Zr-trastuzumab for HER2 imaging

Also known as: Zirconium 89 labelled trastuzumab

T-DM1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Jules Bordet Institute: lead
• Roche Pharma AG: collaborator

Study Sites (5)

Universitair Ziekenhuis Antwerpen (UZA)

Antwerp, Edegem, 2650, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Vrije Universiteit Amsterdam (VUMC)

Amsterdam, 1081HV, Netherlands

Location

University Medical Center Groningen (UMCG)

Groningen, 9700RB, Netherlands

Location

Radboud University Medical Centre Nijmegen (UMCN)

Nijmegen, 6525 GA, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 26598545 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Ado-Trastuzumab Emtansine; zirconium-89-trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Patrick Flamen, MD/PhD

  Jules Bordet Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2012
• First Posted: March 28, 2012
• Study Start: May 1, 2012
• Primary Completion: July 1, 2017
• Study Completion: December 1, 2022
• Last Updated: March 31, 2025

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

BE (2); NL (3)