Description:
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.
Title
- Brief Title: Adjuvant Trastuzumab, Pertuzumab Plus Docetaxel in the Treatment of Early HER2-positive Breast Cancer
- Official Title: 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
Clinical Trial IDs
- ORG STUDY ID:
FBCG-01-2015
- SECONDARY ID:
2015-002323-25
- NCT ID:
NCT02625441
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Pertuzumab | Perjeta | Short anti-HER2 treatment |
| Trastuzumab | Herceptin | Standard anti-HER2 treatment |
Purpose
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 700 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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Short anti-HER2 treatment | Experimental | 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 | |
| Standard anti-HER2 treatment | Active Comparator | 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 | |
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 > 1.
- 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.
- Major surgery (except breast surgery) within 4 weeks prior to study treatment start,
or lack of complete recovery from the effects of major surgery.
- Participation in any investigational drug study within 4 weeks preceding treatment
start.
- Patients with a history of uncontrolled seizures, central nervous system disorders or
psychiatric disability judged by the investigator to be clinically significant
precluding study participation.
- Multifocal breast cancer when the largest cancer focus is not HER2-positive.
- History of another malignancy or contralateral invasive breast cancer within the last
five years except cured basal cell carcinoma of skin or carcinoma in situ of the
uterine cervix (exception: patients with bilateral HER2-positive breast cancer are
eligible).
- One or more of the following: Blood hemoglobin < 10.0 g/dL, neutrophils < 1.5 x 109/L;
platelet count < 120 x 109/L; Serum/plasma creatinine > 1.5 x Upper Limit of Normal
(ULN); Serum/plasma bilirubin > ULN; Serum/plasma ALT and/or AST > 1.5 x ULN;
Serum/plasma alkaline phosphatase > 2.5 x ULN
- Serious uncontrolled infection or other serious uncontrolled concomitant disease.
- Unwilling or unable to comply with the protocol for the duration of the study.
- History of hypersensitivity to the investigational products or to drugs with similar
chemical structures.
- Pre-existing motor or sensory neurotoxicity of a severity ≥ grade 2 by CTCAE version
4, unless related to mechanical etiology.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Female |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Invasive disease-free survival |
| Time Frame: | 7 years |
| Safety Issue: | |
| Description: | Time from the date of randomization to cancer recurrence or death. |
Secondary Outcome Measures
| Measure: | Overall survival |
| Time Frame: | 7 years |
| Safety Issue: | |
| Description: | Time from the date of randomization to death. |
| Measure: | Distant disease-free survival |
| Time Frame: | 7 years |
| Safety Issue: | |
| Description: | Time from the date of randomization to distant recurrence of cancer or to death. |
| Measure: | Left ventricle ejection fractions |
| Time Frame: | 3 years |
| Safety Issue: | |
| Description: | Cardiac ejection fraction measured with echocardiography or isotope cardiography. |
| Measure: | Adverse events of the treatments |
| Time Frame: | 7 years |
| Safety Issue: | |
| Description: | Adverse events considered to be related to the treatments. |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Helsinki University Central Hospital |
Trial Keywords
- Breast cancer
- docetaxel
- pertuzumab
- trastuzumab
- HER2
Last Updated
November 3, 2020
