Randomized phase II study comparing pertuzumab, trastuzumab and anaromatase inhibitor vs. trastuzumab and an aromatase inhibitor inpatients with HER2 and ER/PgR positive breast cancer

Phase 1

• Conditions: HER2- and hormone receptor-positive advanced (metastatic or locally advanced) breast cancer.; MedDRA version: 14.1Level: LLTClassification 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: EUCTR2011-002132-10-IT
• Lead Sponsor: ROCHE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-12-19
• Last Update Posted: 30 November 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 258

Inclusion Criteria

1. Signed written informed consent approved by the Institutional Ethical
Review Board (IRB).
2. Age greater than or equal to 18 years.
3. Postmenopausal status >1 year (fulfilling one or more of National Comprehensive Cancer Network [NCCN] guideline criteria, Version 2.2011).
4. Histologically or cytologically confirmed and documented
adenocarcinoma of the breast with metastatic or locally advanced disease not amenable to curative resection.
5. HER2-positive (defined as either IHC 3+ or 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).
6. Hormone receptor-positive defined as ER-positive and/or PgR-positive assessed locally as defined by institutional criteria.
7. 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).
8. ECOG performance status 0 or 1.
9. Left ventricular ejection fraction (LVEF) of at least 50%.
10. Life expectancy of at least 12 weeks.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion Criteria

1. Previous systemic non-hormonal anticancer therapy in the metastatic or locally advanced breast cancer setting.
2. Disease-free interval from completion of adjuvant or neo-adjuvant
systemic non-hormonal treatment to recurrence of within 6 months.
3. Previous approved or investigative anti-HER2 agents in any breast cancer treatment setting, except trastuzumab and/or lapatinib in the neoadjuvant or adjuvant setting.
4. Disease progression while receiving trastuzumab and/or lapatinib in the adjuvant setting.
5. History of persistent grade 2 or higher (NCI-CTC, Version 4.0) hematological toxicity resulting from previous adjuvant or neo-adjuvant therapy.
6. Radiographic evidence of central nervous system (CNS) metastases as assessed by CT or MRI.
7. Current peripheral neuropathy of grade 3 or higher (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 reatment 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).
• AST (SGOT) or ALT (SGPT) >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) <1.5 × ULN.
• 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 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 edication,
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 randomization or anticipation of need for major surgery during the course of study treatment.
15. Lack of physical integrity of the upper gastrointestinal tract,
clinically significant malabsorption syndrome, or inability to take oral medication.
16. Receipt of intravenous antibiotics for infection within 14 days prior to randomization.
17. Current chronic daily treatment with corticosteroids (dose of 10 mg/day methylprednisolone equivalent), excluding inhaled steroids.
18. Known hypersensitivity to any of the study medications or to excipients of recombinant human or humanized antibodies.
19. History of receiving any investigational treatment within 28
days prior to randomization.
20. Concurrent participation in any clinical trial.
Et al.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: •Confrontare la sopravvivenza libera da progressione (PFS) con pertuzumab somministrato in associazione a trastuzumab più un inibitore dell'aromatasi (IA) rispetto a trastuzumab più un IA.;Secondary Objective: plus an AI versus trastuzumab plus an AI with respect to:<br>• Overall survival (OS)<br>• Overall response rate (ORR)<br>• Clinical benefit rate (CBR)<br>• Duration of response<br>• Time to response<br>• Safety and tolerability<br>• Quality of life (EQ-5D questionnaires);Primary end point(s): The primary efficacy endpoint is Progression-Free Survival (PFS).;Timepoint(s) of evaluation of this end point: Analysis of PFS will be performed when 165 events have occurred.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The secondary efficacy endpoints are:<br>• Overall survival (OS)<br>• Overall response rate (ORR)<br>• Clinical benefit rate (CBR)<br>• Duration of response<br>• Time to response;Timepoint(s) of evaluation of this end point: A first analysis of OS will be performed with the final analysis of PFS.<br>The final analysis of OS will take place once all patients have been<br>followed up for at least 24 months after the last patient is randomized,<br>unless they have been lost to follow-up, withdrawn consent, or died,<br>whichever occurs first. All other secondary endpoints will be summarized<br>with the final analysis of PFS.