EARLY AND LOCALLY ADVANCED HER2-POSITIVE BREAST CANCER
Conditions
Interventions
Product Name: Herceptin for SC injection
Product Code: Ro 045-2317/F07
Pharmaceutical Form: Solution for injection
INN or Proposed INN: TRASTUZUMAB
CAS Number: 180288-69-1
Concentration unit: mg/ml mi
Sponsors
ROCHE SPA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female and male patients aged = 18 years 2. Signed informed consent before any specific study procedure 3. Able and willing to comply with protocol 4. Eastern Cooperative Oncology Group (ECOG) performance status 0–1 5. Pre and post-menopausal status 6. HER2-positive disease immunohistochemistry (IHC) 3+ or in situ hybridization (ISH) positive, as determined in a local laboratory that is experienced/certified in HER2-expression testing using an accurate and validated assay 7. Estrogen and progesterone receptor status (ER and PgR) assessed as negative or positive 8. Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast. Stage of disease: T1-4, N0-3, M0. For T1a-b concomitant axillary involvment is required). 9. Left ventricular ejection fraction (LVEF) of = 55% measured by echocardiography (ECHO) or multiple gated acquisition (MUGA) scan prior to first dose of trastuzumab SC 10. Availability of formalin–fixed paraffin-embedded (FFPE) tissue block or partial block from diagnostic core biopsy (only neoadjuvant patients) and from surgical specimens (both adjuvant and neoadjuvant patients), with representative invasive part of the tumor for additional biomarker analysis 11. Intact skin at site of SC injection on the thigh Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 180 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: Exclusion Criteria 1. History of other malignancy which could affect compliance with the protocol or interpretation of results Patients with curatively treated carcinoma in situ of the cervix or basal cell carcinoma, and patients with other curatively treated malignancies, other than breast cancer, who have been disease-free for at least 5 years, are eligible 2. Severe dyspnea at rest or requiring supplementary oxygen therapy 3. Concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness 4. Serious cardiac illness or medical conditions that would preclude the use of trastuzumab, specifically: history of documented congestive heart failure (CHF), high-risk uncontrolled arrhythmias, angina pectoris requiring medication, clinically significant valvular disease, evidence of transmural infarction on electrocardiogram (ECG), diagnosed poorly controlled hypertension 5. Known infection with human immunodeficiency virus (HIV), active hepatitis B virus (HBV) or hepatitis C virus (HCV) 6. Pregnant or lactating women. Positive serum pregnancy test in women of childbearing potential, premenopausal or less than 12 months of amenorrhea post-menopause, within 7 days prior to the first dose of study drug 7. Women of childbearing potential, premenopausal or less than 12 months of amenorrhea post-menopause (unless surgically sterile), and male patients with partners of childbearing potential who are unable or unwilling to use adequate contraceptive measures during study treatment. In this study, menopause is defined as a minimum of 12 consecutive months of amenorrhea during which time no other biological or physiological cause had been identified as a potential cause of this state. Examples of adequate contraceptive measures are intrauterine device, barrier method (condoms, diaphragm) also in conjunction with spermicidal jelly, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not acceptable 8. Concurrent enrolment in another clinical trial using an investigational anti-cancer treatment, including hormonal therapy, bisphosphonate therapy and immunotherapy, within 28 days prior to the first dose of study treatment 9. Known hypersensitivity to trastuzumab, murine proteins, to any of the excipients of Herceptin® including hyaluronidase, or the adhesive of the SC device (for cohort B), or a history of severe allergic or immunological reactions, e.g. difficulty to control asthma 10. No compliance or adherence with the requirements of the protocol 11. Inadequate bone marrow function (as indicated by any of the following): a) Absolute neutrophil count (ANC) 1.5 × upper limit of normal (ULN) b) Alanine amino transferase (ALT) and/or aspartate amino transferase (AST) > 2.5 × ULN c) Alkaline phosphatase (ALP) > 2.5 × ULN 13. Inadequate renal function, as indicated by serum creatinine > 1.5 × ULN 14. Hormonal treatment concomitant with chemotherapy (allowed in adjuvant phase with adjuvant Trastuzumab SC.) 15. Pre-existing motor or sensory neuropathy of Grade >1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to assess the safety and tolerability of trastuzumab solution injected subcutaneously (vial or single-use injection device [SID]) in patients with HER2-positive early breast cancer (eBC) or locally advanced breast cancer (LABC);Secondary Objective: -Exposure to study medication -Duration of treatment, follow-up, and safety observation -Efficacy: -DFS, OS -In the Neo-adjuvant setting activity of two sequential drug regimens, Anthracycline-containing regimen followed by concomitant administration of Taxane and Trastuzumab SC, assessed as the incidence of pathological Complete Response in breast and nodes (pCR; ypT0-is ypN0) -Patient Satisfaction using SID -HCP satisfaction Explorative Secondary Objective: - assessment of PI3K mutation in tumor tissues and in circulating free DNA (cfDNA) in blood, performed: -to evaluate the agreement between the PI3K mutation assessment in tumor tissue (gold standard) and in circulating free DNA (experimental) -to correlate the baseline mutation status (in tumor tissue and cfDNA) with clinical outcome (pathological response to treatment in the neoadjuvant arm) -to correlate the pharmacodynamic change of the cfDNA before and after treatment with clinical outcome;Primary end point(s): Adverse event (AE) collection will be the primary endpoint for this study. Summaries to be produced will include: ? Incidence and severity by NCI CTCAE version 4.0 of AEs and serious adverse events (SAEs) ? AEs leading to premature discontinuation of study treatment ? Cardiac safety ? Cardiac AEs ? CHF (according to NCI CTCAE version 4.0 and New York Heart Association [NYHA] Classification) ? LVEF over time. In the event of an asymptomatic decline in LVEF, an algorithm (Appendix 2 in the protocol) will be used to determine whether to continue trastuzumab SC treatment;Timepoint(s) of evaluation of this end point: The primary analysis of safety endpoints will be performed after all patients have comple | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary objectives include: -Secondary safety assessments will include the following: ? Exposure to study medication ? Duration of treatment, follow-up, and safety observation ? ECOG ? Concomitant medications Pag. 15 of 119 Trastuzumab—Roche S.p.A. Protocol ML28879, Version 1.0 dated 08-07-2013 ? Laboratory data, vital signs and physical examination ? Premature withdrawals and major protocol violations - Efficacy outcome measures will be evalueted by: ? DFS, OS ?Diagnosis of breast cancer relapse will be made based on routine clinical, radiological and laboratory criteria. In case of uncertainly, disease progression should be confirmed by histological or cytological examination of a suspicious lesion, if possible. In the Neo-adjuvant setting, the activity of two sequential drug regimens, Anthracycline-containing regimen followed by concomitant administration of Taxane and Trastuzumab SC, will be assessed as the incidence of pathological Complete Response in breast and nodes (pCR) (ypT0-is ypN0). Residual in situ disease (ypTis) is considered as pCR. - Patient Satisfaction will be assessed by Patient Satisfaction Questionnaire only in Cohort B (use of Trastuzumab SC SID). In Cohort B, a questionnaire will be completed by patients able to use SID, who completed a minimum of 14 administrations of trastuzumanb SC using SID ( at least 10 self- administered). Health Care Professional (HCP) satisfaction will be assessed by a Health Care Professional Questionnaire (HCPQ). A questionnaire will be completed by both the Investigator and a study nurse at each site when at least 4 patients from their site have received at least 5 cycles of adjuvant study treatment. (For that recruit <4 patients, the investigator and a study nurse will each complete an HCPQ when the last patient at their site has received at least 5 cycles of study treatment).;Timepoint(s) of evaluation of this end point: A preliminary analysis of secondary endpoints | — |
Countries
Italy
Contacts
Public ContactMedical Affairs&Clinical Operations
Roche S.p.A.
Outcome results
None listed