Pertuzumab + trastuzumab (PH) versus PH plus metronomic chemotherapy (PHM) in the elderly HER2+ metastatic breast cancer population who may continue on T-DM1 alone following disease progression while on PH / PHM: an open-label multicentre randomized phase II selection trial of the EORTC Elderly Task Force and Breast Cancer Group

Phase 2

Completed

Conditions: mBC
metastatic breast cancer
10006291

Registration Number: NL-OMON41641

Lead Sponsor: EORTC

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 7

Inclusion Criteria

-Female or male patients with histologically proven HER-2 positive (IHC 3+ or or
HER-2 gene amplification by in situ hybridization [FISH, SISH].
-Patientsmust have measurable (RECIST v. 1.1) or evaluable disease
-Performance status (PS) 0-3 (WHO)
-Age >= 70 years of age, or >= 60 years old with required number of
dependencies as described below :
•65 - 69 in combination with functional restriction defined as limitation
in at least 2 of 8 iADL or 1 of 6 ADL or Charlson comorbidity score > 2
•60 - 64 in combination with functional restrictions defined as
limitation in at least 3 of 8 iADL 2 of 6 ADL or Charlson comorbidity score
> 3
-Life expectancy of more than 12 weeks
-Previous adjuvant chemotherapy/anti HER-2 therapy after surgery is
allowed, given that the time interval from end of previous treatment to
initiation of treatment for metastatic disease is >=6 months.
-Up to one line of anti-HER therapy (trastuzumab or lapatinib) is allowed
in combination with hormone therapy for hormone sensitive metastatic
breast cancer.
-Adequate organ function, evidenced by the following laboratory results
within 3 weeks prior to randomization: (patients with a buffer range
from the normal values of +/- 5% for hematology and +/- 10% for
biochemistry [with the EXCEPTION of Glomerular Filtration Rate] are
acceptable)
-Absolute neutrophil count > 1500 cells/mm3
-Platelet count > 100,000 cells/mm3
-Hemoglobin > 8.5 g/dL
-Total bilirubin <= 1.5 upper limit of normal (ULN)
-SGOT (AST), SGPT (ALT), and alkaline phosphatase <= 2.5× ULN (for
alkaline phosphatase limit applies in the absence of bone metastases)
-Glomerular Filtration Rate (GFR) >= 30 ml/min according to MDRD
formula or Cockcroft and Gault Formula
-Absence of any psychological, familial, sociological or geographical
condition potentially hampering compliance with the study protocol and
follow-up schedule; those conditions should be discussed with the
patient before registration in the trial
-Before patient randomization, written informed consent must be given
according to ICH/GCP, and national/local regulations.
-Newly diagnosed or recurrent (after surgery) stage IV disease
(TNM/AJCC v.7).

Exclusion Criteria

-Current symptomatic brain metastases.
-Prior chemotherapy for metastatic disease.
-Prior treatment with pertuzumab.
-History of exposure to the following cumulative doses of anthracyclines:
•Doxorubicin or liposomal doxorubicin > 360 mg/m2
•Epirubicin > 720 mg/m2
•Mitoxantrone > 120 mg/m2
•Idarubicin > 90 mg/m2
•If another anthracycline or more than 1 anthracycline has been used,
then the cumulative dose must not exceed the equivalent of 360 mg/m2
of doxorubicin.
-History of palliative radiotherapy within 14 days of /prior to randomization.
-History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell or spinocellular carcinoma of the skin.
-Current uncontrolled hypertension (persistent systolic > 180 mmHg
and/or diastolic > 100 mmHg) (with or without medication).
-LVEF below 50%.
-History of significant cardiac disease defined as:
•Symptomatic CHF (NYHA classes II-IV, see Appendix C)
•High-risk uncontrolled arrhythmias, i.e. atrial tachycardia with a heart
rate > 100/min at rest, significant ventricular arrhythmia (ventricular
tachycardia) or higher-grade AV-block (second degree AV-block Type 2
[Mobitz 2] or third degree AV-block)
•History of myocardial infarction within 6 months prior to randomization
•Clinically significant valvular heart disease
•angina pectoris requiring anti-angina treatment
-Peripheral neuropathy of Grade >=3 per NCI CTCAE version 4.0.
current severe, uncontrolled systemic disease (e.g., clinically significant
cardiovascular, pulmonary, or metabolic disease; wound healing
disorders; ulcers; or bone fractures, known infection with HIV, active
hepatitis B and/or hepatitis C virus)
-Major surgical procedure or significant traumatic injury within 28 days
prior to randomization or anticipation of the need for major surgery
during the course of study treatment.
-History of receiving any investigational treatment within 28 days of
randomization.
-History of intolerance (including Grade 3-4 infusion reaction) to
trastuzumab.
-Unwillingness or inability to comply with the requirements of the
protocol as assessed by the investigator.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Progression free survival rate at 6 months</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Overall survival<br /><br>* Breast cancer specific survival<br /><br>Safety<br /><br>* Toxicity (with specific attention to cardiac toxicity);<br /><br>* Tumor response rate as measured by RECIST v1.1<br /><br>* For those patients receiving T-DM1 after progression: toxicity, tumor<br /><br>response, PFS after starting T-DM1<br /><br>* Evolution of HRQoL as assessed by EORTC QLQ-C30 and ELD 15<br /><br>* Evolution of geriatric assessment during treatment. This will be based<br /><br>on the EORTC minimum dataset (G8, IADL and social situation), the<br /><br>ADL and frailty assessment by SPPB.<br /><br>-PFS outside of the brain after brain-only relapse for patients continuing on<br /><br>the treatment they were receiving before brain disease progression (PH or PHM<br /><br>or T-DM1)</p><br>