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: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-02-05
• Study Completion: 2022-08-11
• Last Update Posted: 23 October 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• 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, SISH 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).
- No current symptomatic brain metastases or if previously present, must have been treated at least two months before randomization. CT or MRI scan of the brain is mandatory (within 4 weeks prior to randomization) if there is clinical suspicion of brain metastases.
- Patients must 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 or 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.
- No prior chemotherapy for metastatic disease is allowed
- No prior treatment with pertuzumab is allowed
- No 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.
- No history of palliative radiotherapy within 14 days prior to randomization
- No 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
- No current uncontrolled hypertension (persistent systolic > 180 mmHg and/or diastolic > 100 mmHg) (with or without medication).
- No LVEF below 50%
- No history of significant cardiac disease defined as:
- Symptomatic CHF (NYHA classes II-IV,)
High-risk uncontrolled arrhythmias, i.e. atrial tachycardia with a heart rate > 100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or highergrade AV-block (2nd
degree AV-block Type 2 [Mobitz 2] or 3rd degree AV-block)
- History of myocardial infarction within 6 months prior to randomization
- Clinically significant valvular heart disease
- No angina pectoris requiring anti-angina treatment
- No peripheral neuropathy of Grade =3 per NCI CTCAE version 4.0.
- 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 GFR] are acceptable)
- Absolute neutrophil count > 1500 cells/mm3
- Platelet count > 100,000 cells/mm3
- Hemoglobin > 8.5 g/dL
- Total bilirubin = 1.5 ULN
- SGOT (AST), SGPT (ALT), and ALP= 2.5× ULN (for ALP limit applies in the absence of bone metastases)
- GFR = 30 ml/min a

Exclusion Criteria

-No brain metastases that are untreated, symptomatic, or require steroids to control symptoms; or any radiation, surgery, or other therapy to control symptoms from brain metastases within 2 months prior to the first study treatment.
-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