A Randomized Phase III Study Comparing Trastuzumab, Pertuzumab Plus Docetaxel (TPD) Followed by 3 Cycles of Chemotherapy to the Current Standard Regimen as the Treatments of Early Breast Cancer
Overview
- Phase
- Phase 3
- Intervention
- Pertuzumab
- Conditions
- Breast Cancer
- Sponsor
- Helsinki University Central Hospital
- Enrollment
- 516
- Locations
- 1
- Primary Endpoint
- Invasive disease-free survival
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief Summary
This randomized clinical trial compares two systemic treatments for HER2-positive breast cancer. The treatments are given either prior to breast surgery (as neoadjuvant treatment) or after breast surgery (as adjuvant treatment). In the investigational group (Group A) the study participants will receive a combination of two drugs directed at HER2 (two anti-HER2 antibodies) plus a chemotherapy agent (docetaxel) for a brief duration, and the patients allocated to the comparator group (Group B) will be treated with chemotherapy plus one anti-HER2 treatment (trastuzumab) for one year.
Detailed Description
In this study, patients who have been diagnosed with HER2-positive early breast cancer will be randomly allocated in a 1:1 ratio to receive either three 3-weekly cycles of trastuzumab, pertuzumab and docetaxel (TPD) for a total duration of 9 weeks, followed by three further cycles of chemotherapy (Group A) or three 3-weekly cycles of trastuzumab and docetaxel (TD) followed by three further cycles of chemotherapy and single-agent anti-HER2 antibody treatment to complete one year of anti-HER2 treatment (Group B). These systemic treatments may be administered either prior to breast surgery (as neoadjuvant treatment) or after breast surgery (as adjuvant treatment). The study participants are required to have histologically verified breast cancer with a moderate to high risk for breast cancer recurrence despite macroscopically complete surgery for the breast tumor. The moderate/high risk of breast cancer recurrence is defined by presence of cancer in the axillary lymph nodes, or if the axillary lymph nodes do not contain cancer, by presence of a tumor larger than one centimeter in the breast. The study patients are followed up during the study treatments and after their completion with physical examination, blood tests, cardiac tests and, whenever indicated, with imaging. Approximately 520 patients will be randomly allocated to each of the two groups. The study hypothesis is that the regimen containing TPD may be more effective than the Group B treatment despite its brief duration.
Investigators
Heikki Joensuu
Professor, Research Director
Helsinki University Central Hospital
Eligibility Criteria
Inclusion Criteria
- •Patient has provided a written informed consent prior to study-specific screening procedures, with the understanding that she has the right to withdraw from the study at any time, without prejudice.
- •Woman \> 18 years of age.
- •Histologically confirmed invasive breast cancer.
- •HER2-positive breast cancer (preferably assessed with in situ hybridization; CISH, FISH or SISH; if not available with immunohistochemistry 3+)
- •A high risk of breast cancer recurrence with one of the following: i) Pathological N0 with the longest invasive tumor diameter \>10 mm; ii) Histologically confirmed regional node positive disease
Exclusion Criteria
- •Presence of distant metastases.
- •Inflammatory breast cancer.
- •Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmia not well controlled with medication) or myocardial infarction within the last 12 months.
- •Left ventricular ejection fraction less than 50% (or under the institutional normal reference range) assessed by echocardiography or isotope cardiography.
- •ER and HER-2 status (via in situ hybridization or immunohistochemistry) not determined.
- •The WHO performance status \>
- •Pregnant or lactating women.
- •Women of childbearing potential unless using a reliable and appropriate contraceptive method. Women must have been amenorrheic for at least 12 months prior to study entry to be considered postmenopausal and to have no childbearing potential. Women of childbearing potential (menstruating within 12 months of study entry), or with no hysterectomy and age \< 55, must have a negative pregnancy test at baseline.
- •Randomization more than 12 weeks after the date of breast surgery.
- •Organ allografts with immunosuppressive therapy required.
Arms & Interventions
Short anti-HER2 treatment
Pertuzumab 840 mg, i.v., then 420 mg i.v., 3-weekly for 3 cycles; Trastuzumab 8 mg/kg, i.v., then 6 mg/kg, 3-weekly for 3 cycles; Docetaxel 75 mg/m2, i.v., 3-weekly for 3 cycles
Intervention: Pertuzumab
Standard anti-HER2 treatment
Trastuzumab 8 mg/kg, i.v., then 6 mg/kg, 3-weekly for 3 cycles; Docetaxel 75 mg/m2, i.v., 3-weekly for 3 cycles; Trastuzumab 6 mg/kg, i.v., 3-weekly for for a total duration of one year
Intervention: Trastuzumab
Outcomes
Primary Outcomes
Invasive disease-free survival
Time Frame: 7 years
Time from the date of randomization to cancer recurrence or death.
Secondary Outcomes
- Overall survival(7 years)
- Left ventricle ejection fractions(3 years)
- Distant disease-free survival(7 years)
- Adverse events of the treatments(7 years)