A trial of Pertuzumab and Herceptin versus Pertuzumab and Herceptin and metronomic chemotherapy in elderly patients with Her2 positive metastatic breast cancer, with the option to receive TDM-1 at disease progressio

Phase 1

• Conditions: ewly diagnosed or recurrent (after surgery) stage IV (TNM/AJCC v.7) HER-2 positive (IHC 3+ or or HER-2 gene amplification by in situ hybridization) invasive breast cancer; MedDRA version: 18.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-006342-32-PT
• Lead Sponsor: EORTC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-06-19
• Study Completion: 2022-08-11
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

- patients with histologically proven HER-2 positive (IHC 3+ or or HER-2 gene amplification by in situ hybridization [FISH, SIS-Patients must have measurable (RECIST v. 1.1) or evaluable disease (please refer to chapter 7)
-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 (see Appendix D)
-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.
mula or Cockcroft and Gault Formula (see Appendix D)H or CISH]) invasive breast cancer, based on the results of local laboratories of the participating centers. All histologies are eligible.
-Newly diagnosed or recurrent (after surgery) stage IV disease (TNM/AJCC v.7).
Evaluate the evolution of potential ageing biomarkers and their predictive potential for toxicity, decline in functionality and fraility status and outcome.
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 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70

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 clinical trial of medicinal product
• Study Design: Not specified