A Phase III Trial of Pertuzumab Retreatment in Previously Pertuzumab Treated Her2-Positive Advanced Breast Cancer (PRECIOUS)
HER2-positive Locally Advanced or Metastatic Breast Cancer
About this trial
This is an interventional treatment trial for HER2-positive Locally Advanced or Metastatic Breast Cancer
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed invasive breast cancer
- A confirmed HER2-positive status assessed by means of immunohistochemical analysis (with 3+ indicating positive status) and/or in situ hybridization (with an amplification ratio > 2.0 indicating positive) by each institute
- History of pertuzumab and trastuzumab-containing chemotherapy for locally advanced and metastatic breast cancer(2 or 3 regimen as previous chemotherapy regimen for locally advanced or metastatic breast cancer). The latest regimen before enrollment dose not include pertuzumab.
- Patients have measurable and/or non-measurable disease according to RECIST ver1.1.
- Female patients and aged ≥ 20 years.
- Left Ventricular Ejection Fraction (LVEF) > 50% at baseline (within 28 days before enrollment) as determined by either ECHO or MUGA
- Eastern Cooperative Oncology Group performance status of 0,1 or 2.
- Life expectancy of patients is expected at least 3 months.
- Signed and written informed consent (approved by the Institutional Review Board or Independent Ethics Committee) is obtained before any study procedure.
Exclusion Criteria:
- History of chemotherapy > 4 regimen for locally advance or metastatic disease except for cancer chemotherapeutic agent-free treatment regimen (eg, hormonal therapy alone, combination with hormonal therapy and trastuzumab and anti-HER2 therapy alone).
- Persistent Grade >3 non-hematologic toxicity according to NCI-CTCAE v4.0-JCOG resulting from previous therapy at the time of enrollment.
- Symptomatic or uncontrolled central nervous system metastases.
- Multiple malignancies without history of breast cancer(within 10 years if invasive breast cancer and within 5 years if malignancies except invasive breast cancer)
History of exposure to the following cumulative doses of anthracyclines:
- doxorubicin or liposomal doxorubicin > 360 mg/m2
- epirubicin > 720 mg/m2
- mitoxantrone > 100 mg/m2
- If more than 1 anthracycline has been used, then the cumulative dose must not exceed the equivalent of 360 mg/m2 of doxorubicin.
- Current uncontrolled hypertension (systolic > 150 mmHg and/or diastolic > 100 mmHg) or unstable angina.
- History of CHF of any New York Heart Association criteria, or serious cardiac arrhythmia requiring treatment (exception, atrial fibrillation, paroxysmal supraventricular tachycardia).
- History of myocardial infarction within 6 months of enrollment.
- Dyspnea at rest due to complications of advanced malignancy.
Inadequate organ function, as determined by the following laboratory results, within 28 days before enrollment:
- Absolute neutrophil count < 1,500/mm3
- Platelet count < 100,000/mm3
- Hemoglobin < 8.0 g/dL
- Total bilirubin > 2.0 mg/dL, unless the patient has documented Gilbert's syndrome
- Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) > 100IU /L with the following exception (If considered that the liver dysfunction due to liver metastases > 200 IU/L, or 100 < , ≤200 IU/L with serum albumin < 2.5 g/dL)
- Serum creatinine value > 2.0 mg/dL or 177 μmol/L
Current severe uncontrolled systemic disease(eg. Clinically significant cardiovascular, pulmonary and metabolic disease*, disorder of wound healing, ulcer and fracture)
*If gemcitabine is planned to be selected as a combination chemotherapeutic agent,patients who has symptomatic interstitial pneumonia or pulmonary fibrosis on chest X-ray should be excluded.
- Uncontrolled malignancy-associated hypercalcemia syndrome under bisphosphonates or denosumab treatment.
- Radiation related grade >2 adverse event within 14 days before enrollment.
- Major surgical procedure or significant traumatic injury within 28 days before enrollment or anticipation of need for major surgery during the course of study treatment.
- Pregnant woman or positive pregnancy test.
- Nursing woman
- History of receiving any investigational treatment within 28 days before enrollment.
- Current known and active infection with human immunodeficiency virus, hepatitis B virus or hepatitis C virus.
- Receipt of intravenous antibiotics for infection within 14 days before enrollment.
- Current chronic daily treatment (continuous for > 3 months) with corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled steroids.
- Known hypersensitivity to pertuzumab or trastuzumab without infusion reaction related to these drugs
- Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.
Sites / Locations
- Aichi Cancer Center
- Kumamoto University Hospital
- Japan Breast Cancer Research Group
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
Trastuzumab + chemotherapy
Trastuzumab+ pertuzumab + chemotherapy
Trastuzumab + chemotherapy Chemotherapy regimen is chosen from the following; Docetaxel, Paclitaxel, nab-paclitaxel ,Vinorelbine, Eribulin, Capecitabine or Gemcitabine
Trastuzumab+ pertuzumab + chemotherapy Chemotherapy regimen is chosen from the following; Docetaxel, Paclitaxel, nab-paclitaxel, Vinorelbine, Eribulin, Capecitabine or Gemcitabine