Locally recurrent (not amenable to resection with curative intent) or metastatic disease scheduled for a first or any subsequent metastatic treatment line MedDRA version: 23.0 Level: PT Classification code 10065430 Term: HER2 positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant
Conditions
Interventions
Trade Name: KADCYCLA
Product Name: trastuzumab-MCC-DM1
Product Code: RO5304020/F02
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: ado-trastuzumab emtansine
Sponsors
Jules Bordet Institute
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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 2. 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. 3. 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. 4. 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. 5. Age = 18 years 6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1 7. No significant cardiac history and current LVEF = 50% 8. 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) =65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Patients with bone only metastases are not eligible. 2. Diffuse liver (=50%) involvement on imaging. 3. 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. 4. Current uncontrolled hypertension despite medication intake (systolic ? 150 mmHg and/or diastolic ? 100 mmHg) 5. Current unstable angina 6. History of symptomatic CHF of any New York Heart Association (NYHA) criteria or ventricular arrhythmia that requires treatment 7. History of myocardial infarction within the last 6 months 8. History of a decrease in LVEF to < 40% or symptomatic CHF with previous trastuzumab treatment 9. Current dyspnea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy 10. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures) 11. 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 12. Pregnant or lactating women 13. Concurrent, serious, uncontrolled infections or current known infection with HIV, active hepatitis B and/or hepatitis C. 14. Known prior severe hypersensitivity to trastuzumab 15. Patient who received lapatinib within the 15 days prior to 89Zr-Trastuzumab injection 16. Patient under a prohibited concomitant therapy, including vitamine K antagonist (see Section 7.1.7 concomitant therapy) 17. Patients with a peripheral neuropathy Grade 3 or higher
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to show, on a lesion-based analysis, 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). ;Secondary Objective: 1: 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. 2: 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 3: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. 4: Other secondary endpoints are exploratory. (Cf protocol section 3.3) ;Primary end point(s): The primary endpoint for this study is the negative predictive value (NPV) of the 89Zr-trastuzumab PET/CT, defined as the proportion of lesions with a negative imaging test result which will be classified as non responding lesions (stable or progressive) after 3 cycles of T-DM1. ;Timepoint(s) of evaluation of this end point: after 3 cycles of T-DM1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1/Negative predictive value of the early FDG PET/CT, defined as the proportion of lesions without an early metabolic response that will be classified as non responding lesions after 3 cycles of T-DM1 according to anatomic and metabolic criteria. 2/Negative predictive value of the 89Zr-trastuzumab PET/CT, defined as the proportion of lesions with a negative HER2 imaging test result that will be classified as non responding lesions after 3 cycles of T-DM1 according to metabolic criteria. 3/Negative predictive value of the combined 89Zr-trastuzumab PET/CT and early PET/CT. The NPV is defined as the proportion of lesions with a negative HER2 imaging test result and a non responding classification on the early FDG-PET/CT that will be classified as non responding lesions after 3 cycles of T-DM1 according to metabolic and morphological criteria. Other secondary endpoints are exploratory. (Cf protocol section 3.3);Timepoint(s) of evaluation of this end point: end of the study | — |
Countries
Belgium, Netherlands
Contacts
Public ContactGebhart Geraldine
Jules Bordet Institute
Outcome results
None listed