Breast Cancer
Conditions
Brief summary
To investigate clinical positioning between trastuzumab (Herceptin) monotherapy (H group) and combination therapy of trastuzumab and chemotherapy (H+CT group) based on a randomized controlled trial in women over 70 years with human epidermal growth factor receptor type-2 (HER2) positive primary breast cancer.
Detailed description
This study is a randomized, comparative trial of postoperative adjuvant therapies in women with HER2 (human epidermal growth factor receptor type-2)-positive primary breast cancer who are ≥70 years of age that will compare trastuzumab (Herceptin®) monotherapy (H group) and trastuzumab in combination with chemotherapy (H+CT group). The objectives of this study are as follows. 1. To verify the clinical positioning of trastuzumab monotherapy and combined trastuzumab and chemotherapy as postoperative adjuvant therapies for the treatment of HER2-positive primary breast cancer patients who are ≥70 years of age. 2. To evaluate the safety of trastuzumab monotherapy and combined trastuzumab and chemotherapy in patients who are ≥70 years of age. In particular, to evaluate cardiac disorders that are a characteristic adverse drug reaction of trastuzumab as well as geriatric-related concerns including lipid metabolism, cerebral infarction and cognitive disorders. 3. To evaluate overall survival in patients who are ≥70 years of age using trastuzumab monotherapy or combined trastuzumab and chemotherapy. 4. To evaluate health-related quality of life (HRQOL), cost-effectiveness (utility), and conduct a comprehensive geriatric assessment (CGA) in patients who are ≥70 years of age and using trastuzumab monotherapy or combined trastuzumab and chemotherapy. 5. To establish and expand information networks by the participation of practitioners in clinical trials that are involved in general clinical practice and breast cancer.
Interventions
DRUGtrastuzumab monotherapy
DRUGtrastuzumab and chemotherapy
Sponsors
Comprehensive Support Project for Oncology Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
70 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically diagnosed as invasive breast cancer and received curative operation for primary breast cancer. 2. Stage: 1 (tumor size \[pT\] \> 0.5 cm), 2A, 2B or 3A/ M0 3. Female between 70 and 80 years old 4. Primary region is HER 2 positive: either 3+ overexpression by IHC or positive by FISH 5. Baseline left ventricular ejection fraction (LVEF) is ≥55% measured by echocardiography or MUGA scan within 4 weeks before registration. 6. PS: 0-1 (ECOG) 7. Sufficient organ function meeting following criteria within 4 weeks before registration: * Leukocyte ≥2500 mm3 * Neutrophil ≥1500 mm3 * Platelet ≥100 000 mm3 * Serum total bilirubin ≤2.0 x upper limit of normal (ULN) * ALT (GPT) or AST (GOT) ≤2.5 x ULN * Serum creatinine ≤2.0 x ULN * ALP ≤2.5 x ULN 8. No previous endocrine therapy or chemotherapy for breast cancer 9. Signed written informed consent
Exclusion criteria
1. Active multiple primary cancer (synchronous multiple primary cancer and invasive cancer of other organs) 2. Postoperative histological axillary lymph node metastasis ≥4 3. Axillary lymph node is not histologically evaluated 4. Histologically confirmed positive margin in breast conservation surgery (evaluation of margin status is based on policy of site) 5. History of drug-related allergy which could hinder planned treatment 6. Any history or complication of following cardiac disorders * History of congestive heart failure, cardiac infarction * Complication requires treatment such as: ischemic cardiac disorder, arrhythmia, valvular heart disease 7. Poorly controlled hypertension (ex. Systolic arterial pressure ≥180 mmHg or diastolic blood pressure ≥100 mmHg) 8. Poorly controlled diabetes 9. Continuous visit to a medial institution is considered difficult due to deterioration of activity of daily living (ADL) 10. Difficult to participate in the trial because of psychiatric disorder or psychiatric symptoms 11. Ineligible to the trial based on decision of an investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease free survival | Patients are followed up for 8 years after initial enrollment (from Oct. 2009 through Oct. 2017). | Disease-free survival is defined as the interval from the date of enrollment to the date of any of the following events. 1. Local recurrence, distant metastasis 2. Metachronous breast cancer, secondary cancer 3. Death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | Patients are followed up for 8 years after initial enrollment (from Oct. 2009 through Oct. 2017). | Overall survival is defined as the interval from the date of enrollment to the date of death from any cause. |
| Relapse-free survival | Patients are followed up for 8 years after initial enrollment (from Oct. 2009 through Oct. 2017). | Relapse-free survival is defined as the interval from the date of enrollment to the date of any of the following events. 1. Local recurrence, distant metastasis 2. Death |
| Percentage of participants with adverse events as a measure of safety | Evaluations are performed at the time of starting the specified treatment and 2, 6, and 9 month, 1 year, 1 year 6 months, 2 years, 2 years 6 months, and 3 years after the start of treatment. Subsequently, evaluations are done at 1-year intervals. | The following variables are evaluated: left ventricular ejection fraction, white-cell count, neutrophil count, platelet count, bilirubin level, alanine aminotransferase level, aspartate aminotransferase level, alkaline phosphatase level, and creatinine level. |
| Health-related QOL (HRQOL) | Evaluations are performed at the time of starting the specified treatment and 2 months, 1 year, and 3 years after the start of treatment. | The following QOL questionnaire forms (in Japanese) are used for evaluations: FACT-G, HADS, EQ-5D, and PNQ. |
| Cost effectiveness analysis | Data on direct medical costs for the 3-year period after the start of the treatment are obtained from CRF. Data on direct nonmedical costs and indirect costs are obtained from questionnaires 2, 12, and 36 months after starting the treatment. | Survey items are as follows. 1. Direct medical costs: medical costs associated with therapy, the management of adverse events, etc. 2. Direct nonmedical costs: transportation expenses required for medical examinations, costs of health foods, etc. 3. Indirect costs: work-loss costs associated with treatment that are incurred directly by the patient and by their caregivers |
Countries
Japan
Outcome results
None listed