Comparison of two anti-HER2 agents plus chemotherapy with standard regimen as the treatments of breast cancer that expresses HER2
- Conditions
- Early HER-2 -positive breast cancerTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-002323-25-SE
- Lead Sponsor
- Finnish Breast Cancer Group
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 1366
1. 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.
2. Woman = 18 years of age.
3. Histologically confirmed invasive breast cancer.
4. HER2-positive breast cancer (preferably assessed with in situ hybridization; CISH, FISH or SISH; if not available, immunohistochemistry needs to be 3+)
5. A moderate or 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 (pN+; nodal isolated tumor cells/cell clusters =0.2 mm in diameter (ITP) are not counted as a metastasis, whereas micrometastases >0.2 mm are considered metastases)
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 1000
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 366
1. Presence of distant metastases.
2. Inflammatory breast cancer.
3. 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.
4. Left ventricular ejection fraction less than 50% (or under the institutional normal reference range) assessed by echocardiography or isotope cardiography.
5. ER and HER-2 status (via in situ hybridization or immunohistochemistry) not determined.
6. The WHO performance status > 1.
7. Pregnant or lactating women.
8. 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.
9. Randomization more than 12 weeks after the date of latest breast surgery.
10. Organ allografts with immunosuppressive therapy required.
11. Major surgery (except breast surgery) within 4 weeks prior to study treatment start, or lack of complete recovery from the effects of major surgery.
12. Participation in any investigational drug study within 4 weeks preceding treatment start.
13. 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.
14. Multifocal breast cancer when the largest cancer focus is not HER2-positive.
15. 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).
16. One or more of the following:
• Blood hemoglobin < 100 g/L, neutrophils < 1.5 x 10^9/L, platelet count < 120 x 10^^9/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
17. Serious uncontrolled infection or other serious uncontrolled concomitant disease.
18. Unwilling or unable to comply with the protocol for the duration of the study.
19. History of hypersensitivity to the investigational products or to drugs with similar chemical structures.
20. Pre-existing motor or sensory neurotoxicity of a severity = grade 2 by CTCAE version 4, unless related to mechanical etiology
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Calculate the invasive disease-free survival (IDFS);Secondary Objective: 1. Calculate the overall survival<br>2. Calculate the distant disease-free survival<br>3. Assess the LVEF (left ventricular ejection fraction) change<br>4. Assess the toxicity <br>5. Assess the Quality of Life;Primary end point(s): Invasive disease-free survival;Timepoint(s) of evaluation of this end point: Defined by the time interval between the date of randomisation and the date of first detection of invasive breast cancer recurrence or death, whichever occurs first. Follow-up 3-week intervals during the first 61 weeks on study in each arm, then annually.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Overall survival<br>2. Distant disease-free survival<br>3. LVEF change<br>4. Safety<br>5. Quality of life<br>;Timepoint(s) of evaluation of this end point: 1. The timeperiod between the date of randomisation and the date of death.<br>2. The time period between the date of randomisation and the date of first detection of distant breast cancer recurrence or death, whichever occurs first. Follow-up 3-week intervals during the first 61 weeks on study in each arm, then annually.<br>3. LVEF collected at weeks 18, 31, 43, 61 and month 36.<br>4. Common terminology Criteria for Adverse Events (CTCAE) version 4.0 collected from randomisation every 3 weeks during the first 61 weeks on study.<br>5. Ouality of Life (EQ-5D instrument) collected from randomisation at cycle 4, week 31, week 43 and month 36.<br>