A multicenter, open-label, single-arm study of pertuzumab in combination with trastuzumab and a taxane in first line treatment of patients with HER2- positive advanced (metastatic or locally recurrent) breast cancer
- Conditions
- Advanced breast cancer (metastatic or locally recurrent)MedDRA version: 21.1Level: PTClassification code 10065430Term: HER-2 positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-005334-20-DE
- Lead Sponsor
- F. Hoffmann-La Roche Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1436
1. Signed written informed consent approved by the relevant Institutional Review Board (IRB), or Independent Ethics Committee (IEC).
2. Male or female patients aged 18 years or over.
3. Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally recurrent disease not amenable to curative resection.
4. HER2-positive (defined as either IHC 3+ or in situ hybridization [ISH] positive) as assessed by local laboratory on primary tumor and/or metastatic site if primary tumor not available (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 (Appendix 5).
6. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 (Appendix 3).
7. LVEF of at least 50%.
8. Negative serum pregnancy test in women of childbearing potential (WOCBP; premenopausal or less than 12 months of amenorrhea post-menopause, and who have not undergone surgical sterilization).
9. For WOCBP and male patients with partners of CBP who are sexually active, agreement to use a highly effective, non-hormonal form of contraception (such as surgical sterilization) or two effective forms of non-hormonal contraception (such as a barrier method of contraception in conjunction with spermicidal jelly) during and for at least 7 months post-study treatment (refer to Section 4.5.2.1 for details).
10. 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 1260
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 240
1. Previous systemic non-hormonal anticancer therapy for the metastatic or locally recurrent disease. Note: Prior to study entry, up to two lines of hormonal therapy for metastatic or locally recurrent disease are permitted, one of which may be in combination with Everolimus.
2. Disease-free interval from completion of adjuvant or neoadjuvant systemic non-hormonal treatment to recurrence within 6 months.
3. Previous approved or investigative anti-HER2 agents in any breast cancer treatment setting, except trastuzumab and/or lapatinib in the adjuvant or neoadjuvant setting.
4. Disease progression while receiving trastuzumab and/or lapatinib in the adjuvant or neoadjuvant setting.
5. History of persistent Grade 2 or higher (National Cancer Institute [NCI]-Common Toxicity Criteria [CTC], Version 4.0) hematological toxicity resulting from previous adjuvant or neoadjuvant therapy.
6. Patients with radiographic evidence of central nervous system (CNS) metastases as assessed by computed tomography (CT) or magnetic resonance imaging (MRI) that are not well controlled (symptomatic or requiring control with continuous corticosteroid therapy (eg dexamethasone)). Note: Patients with CNS metastases are permitted to participate in the study if they are stable in the 3 months prior to screening (as assessed by the investigator) after receiving local therapy (irradiation, surgery etc) but without anti-HER2 therapy.
7. Current peripheral neuropathy of Grade 3 or greater (NCI-CTC, Version 4.0).
8. History of other malignancy within the last 5 years prior to 1st study drug administration (dosing), 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 <1,500 cells/mm3 •Platelet count <100,000 cells/mm3 •Hemoglobin <9 g/dL •Total bilirubin greater than the upper limit of normal (ULN; unless the patient has documented Gilbert’s syndrome) •Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) >2.5 × ULN (> 5 × ULN in patients with liver metastases) •Alkaline phosphatase levels > 2.5 × the ULN (> 5 × ULN in patients with liver metastases, or >10 × ULN in patients with bone metastases) •Serum creatinine >2.0 mg/dL or 177 µmol/L •International normalized ratio (INR) and activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) >1.5 × ULN (unless on therapeutic anti-coagulation).
11. Uncontrolled hypertension (systolic >150 m m Hg and/or diastolic >100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident/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, Hepatitis B virus, or Hepatitis C virus.
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 14 days prior to 1st study drug administration (dosing) or anticipation of need for major surgery during the course of stud
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method