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

• Register: EUCTR
• Last refreshed on: 3 November 2020
• Main ID: EUCTR2011-005334-20-NL
• Date of registration: 05/03/2012
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd.
• Public title: 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
• Scientific title: 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 - PERUSE
• Date of first enrolment: 25/06/2012
• Target sample size: 1500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-005334-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Algeria, Argentina, Australia, Austria, Bahrain, Belgium, Brazil, Canada, China, Ecuador, Egypt, Estonia, European Union, Finland, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Lebanon, Lithuania, Mexico, Morocco, Netherlands, Pakistan, Peru, Poland, Portugal, Saudi Arabia, Serbia, Slovenia, Spain, Sweden, Turkey, Ukraine, United Arab Emirates, United Kingdom, Uruguay, Venezuela, Bolivarian Republic of

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd.

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
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

Exclusion criteria:
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 (e.g. dexamathasone)). 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 tharapy (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 study

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Advanced breast cancer (metastatic or locally recurrent)
MedDRA version: 19.0 Level: PT Classification code 10065430 Term: HER-2 positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Trade Name: Perjeta
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 code: RO4368451
Other descriptive name: rhuMAb 2C4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 420 mg/14 ml-

Primary Outcome(s)

Main Objective: To evaluate the safety and tolerability of pertuzumab in combination with trastuzumab and a taxane.

Secondary Objective: To evaluate pertuzumab in combination with trastuzumab and a taxane with respect to:
•Progression-free survival (PFS)
•Overall survival (OS)
•Overall response rate (ORR)
•Clinical benefit rate (CBR)
•Duration of response
•Time to response
•Quality of life (Functional Assessment of Cancer Therapy- Breast [FACT-B] questionnaire for female patients only).

Timepoint(s) of evaluation of this end point: The final analysis will be done at least 60 months after the last patient has been enrolled into the study or all patients in the study have withdrawn consent, or died, or if the study is prematurely terminated by the Sponsor, whichever occurs first. In addition to the final analysis, there will be five interim safety analyses for review by the IDMC, after approximately 100, 350, 700, 1100 and 1500 patients have been enrolled. There will also be an annual review of safety data by the IDMC following completion of enrollment.

Primary end point(s): Assessment of safety and tolerability

Secondary Outcome(s)

Secondary end point(s): Analysis of efficacy

Timepoint(s) of evaluation of this end point: The final analysis will be done at least 60 months after the last patient has been enrolled into the study or all patients in the study have withdrawn consent, or died, or if the study is prematurely terminated by the Sponsor, whichever occurs first. In addition to the final analysis, there will be five interim safety analyses for review by the IDMC, after approximately 100, 350, 700, 1100 and 1500 patients have been enrolled. There will also be an annual review of safety data by the IDMC following completion of enrollment.

Secondary ID(s)

2011-005334-20-AT

MO28047

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd.

Ethics review

Status: Approved
Approval date: 25/06/2012
Contact:

Results

• Results available: Yes
• Date Posted: 16/09/2020
• Date Completed: 20/09/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-005334-20/results