HER2-positive advanced (metastatic or locally advanced) breast cancer MedDRA version: 14.0 Level: LLT Classification code 10065430 Term: HER-2 positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Pertuzumab (rhuMAb 2C4)
Product Code: RO 4368451/F01
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Pertuzumab
CAS Number: 380610-27-5
Current Sponsor co
Sponsors
F. Hoffmann-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent approved by the relevant Institutional Ethical Review Board (IRB). 2. Female or male patients aged 18 years or older. 3. Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally advanced disease not amenable to curative resection. 4. HER2-positive (defined as either immunohistochemistry [IHC] 3+ or in situ hybridization [ISH] positive) as assessed by local laboratory on primary or metastatic tumor (ISH positivity is defined as a ratio of 2.0 or greater for the number of HER2 gene copies to the number of signals for CEP17, or for single probe tests, a HER2 gene count greater than 4). 5. At least one measurable lesion and/or non-measurable disease evaluable according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 (Eisenhauer et al. 2009). 6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 7. Left ventricular ejection fraction (LVEF) of at least 55%. 8. Negative pregnancy test in women of childbearing potential (premenopausal or less than 12 months of amenorrhea post-menopause, and who have not undergone surgical sterilization). 9. For women of childbearing potential who are sexually active, agreement to use a highly effective, nonhormonal form of contraception or two effective forms of non-hormonal contraception during and for at least 6 months post-study treatment. 10. Fertile males willing and able to use effective nonhormonal means of contraception (barrier method of contraception in conjunction with spermicidal jelly, or surgical sterilization) during and for at least 6 months post-study treatment. 11. Life expectancy of at least 12 weeks. 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 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 110
Exclusion criteria
Exclusion criteria: 1. Previous systemic non-hormonal anticancer therapy in the metastatic or locally advanced breast cancer setting. 2. Previous approved or investigative anti-HER2 agents in any breast cancer treatment setting, except trastuzumab and/or lapatinib in the adjuvant or neoadjuvant setting. 3. Disease progression while receiving trastuzumab and/or lapatinib in the adjuvant or neoadjuvant setting. 4. Disease-free interval from completion of adjuvant or neo-adjuvant systemic non-hormonal treatment to recurrent disease of less than 6 months. 5. History of persistent Grade 2 or higher (NCI-CTC, Version 4.0) hematological toxicity resulting from previous adjuvant or neoadjuvant therapy. 6. Radiographic evidence of central nervous system (CNS) metastases as assessed by computed tomography (CT) or magnetic resonance imaging (MRI). 7. Current peripheral neuropathy of Grade 3 or greater (NCI-CTC, Version 4.0). 8. History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma. 9. Serious uncontrolled concomitant disease that would contraindicate the use of any of the investigational drugs used in this study or that would put the patient at high risk for treatment-related complications. 10. Inadequate organ function, evidenced by the following laboratory results: ? Absolute neutrophil count 2.5 × ULN ? AST (SGOT) or ALT (SGPT) >1.5 × ULN with concurrent serum alkaline phosphatase >2.5 × ULN; Serum alkaline phosphatase may be >2.5 × ULN only if bone metastases are present and AST (SGOT) and ALT (SGPT) 2.0 mg/dL or 177 ?mol/L ? International normalized ratio (INR) and activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) >1.5 × ULN (unless on therapeutic coagulation) 11. Uncontrolled hypertension (systolic >150 mm Hg and/or diastolic >100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident (CVA)/stroke or myocardial infarction within 6 months prior to first study medication, unstable angina, congestive heart failure (CHF) of New York Heart Association (NYHA) Grade II or higher, or serious cardiac arrhythmia requiring medication. 12. Current known infection with HIV, HBV, or HCV. 13. Dyspnea at rest due to complications of advanced malignancy, or other disease requiring continuous oxygen therapy. 14. Major surgical procedure or significant traumatic injury within 28 days prior to enrollment into the study or anticipation of need for major surgery during the course of study treatment. 15. Receipt of intravenous (IV) antibiotics for infection within 14 days prior to enrollment into the study. 16. Current chronic daily treatment with corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled steroids. 17. Known hypersensitivity to any of the study medications or to excipients of recombinant human or humanized antibodies. 18. History of receiving any investigational treatment within 28 days prior to enrollment into the study. 19. Concurrent participation in any clinical trial. 20. Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare objective overall response rates (ORR) assessed by a blinded independent review committee (IRC) of pertuzumab given in combination with trastuzumab and vinorelbine together in a single infusion bag versus conventional sequential administration in separate infusion bags.;Secondary Objective: o ORR assessed by the investigator o Time to response assessed by IRC and investigator o Duration of response assessed by IRC and investigator o Progression free survival (PFS) o Time to progression (TTP) o Overall survival (OS) o Safety and tolerability o Quality of life (EQ-5D and FACT-B questionnaires);Primary end point(s): ORR assessed by IRC according to RECIST version 1.1, based on the best (confirmed) overall response (BOR; defined as the best response recorded from the start of trial treatment until disease progression/recurrence or death).;Timepoint(s) of evaluation of this end point: When all patients have progressed, have been followed up for at least 24 months after the last patient is enrolled into the corresponding cohort, discontinued study medication, withdrawn consent from the study, or died, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? BOR as assessed by the investigator ? Time to and duration of response (in responders) as assessed by the Investigator and IRC ? PFS ? TTP ? OS;Timepoint(s) of evaluation of this end point: Final analysis of PFS and TTP, and the first analysis of OS will be performed at the time of the final analysis of BOR. The final analysis of OS will take place when all patients have been followed up for at least 24 months after the last patient is enrolled into the corresponding cohort, unless they have been lost to follow-up, withdrawn consent, or died, or if the study is prematurely terminated by the Sponsor, whichever occurs first. | — |
Countries
Brazil, Denmark, European Union, Germany, Italy, Spain, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd.
Outcome results
None listed