Breast Cancer
Conditions
Keywords
stage IV breast cancer, recurrent breast cancer
Brief summary
RATIONALE: To compare efficacy, toxicity and quality of life of the sequential administration of Her alone followed, at PD, by the combination with Chemotherapy (Arm A) vs. the upfront combination of Her and Chemotherapy (Arm B) in patients with advanced/metastatic breast cancer. PURPOSE: Trial SAKK 22/99 addresses clinically relevant and currently unresolved questions regarding the optimal use of Herceptin in the treatment of patients with advanced/metastatic breast cancer.
Detailed description
In advanced HER2+ breast cancer the impact of combining Trastuzumab (T) and chemotherapy (chemo) versus T alone followed by the addition of chemo at disease progression has not been properly studied. The trial compared efficacy, toxicity and quality of life of sequential administration of T followed, at progression, by combination with chemo (T\>TChemo) versus the upfront combination of T and chemo (TChemo) in patients with HER2+ advanced breast cancer.
Interventions
DRUGHerceptin™ (Her)
Herceptin™ (Her) loading dose 4 mg/kg iv, followed by 2 mg/kg iv weekly or loading dose 8 mg/kg iv, followed by 6 mg/kg iv every 3 weeks; at time of progression add chemotherapy
DRUGHerceptin™ (Her) + chemo
Herceptin™ (Her) loading dose 4 mg/kg iv, followed by 2 mg/kg iv weekly or loading dose 8 mg/kg iv, followed by 6 mg/kg iv every 3 weeks, and chemotherapy
Sponsors
Swiss Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed HER2-overexpressing metastatic breast carcinoma * Clinically or radiologically measurable or evaluable disease * Bidimensionally or unidimensionally measurable lesions * No ascitic, pleural, or pericardial effusions, osteoblastic bone metastases, or carcinomatous lymphangitis of the lung as only indicator lesion * No known clinical brain or meningeal involvement * Hormone receptor status: * Not specified PATIENT CHARACTERISTICS: Age: * 18 to 70 Sex: * Female Menopausal status: * Not specified Performance status: * ECOG 0-1 OR * SAKK 0-1 Life expectancy: * At least 12 weeks Hematopoietic: * Hemoglobin at least 10 g/dL * Platelet count at least 100,000/mm\^3 * Absolute neutrophil count at least 2,000/mm\^3 Hepatic: * Bilirubin normal * SGOT and/or SGPT no greater than 2 times upper limit of normal (ULN) (3 times ULN if proven liver metastases) OR * No SGOT and/or SGPT greater than 1.5 times ULN if alkaline phosphatase greater than 2.5 times ULN Renal: * Creatinine no greater than 1.25 times ULN Cardiovascular: * LVEF normal * No history of atrial ventricular arrhythmia, congestive heart failure, or angina pectoris, even if medically controlled * No history of second or third-degree heart blocks * No uncontrolled hypertension Other: * Not pregnant or nursing * Fertile patients must use effective contraception * No pre-existing motor or sensory neuropathy grade 2 or greater * No psychiatric disorder that would preclude informed consent * No other prior malignancy except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix * No definite contraindications for use of corticosteroids * No other concurrent serious illness or medical condition PRIOR CONCURRENT THERAPY: Biologic therapy: * Not specified Chemotherapy: * Prior adjuvant or neoadjuvant chemotherapy allowed * No more than 2 prior chemotherapy regimens for metastatic disease * No prior cumulative dose of doxorubicin greater than 240 mg/m\^2 * No prior cumulative dose of epirubicin greater than 360 mg/m\^2 * No prior taxanes Endocrine therapy: * Prior hormonal therapy as adjuvant treatment or for metastatic disease allowed * No concurrent corticosteroids unless started more than 6 months prior to study and at low doses (i.e., no greater than 20 mg methylprednisolone or equivalent) Radiotherapy: * Not specified Surgery: * Not specified Other: * No other concurrent anticancer drugs * No other concurrent experimental drugs * No concurrent bisphosphonates unless initiated more than 3 months prior to study * Chronic use allowed provided bone metastases are not sole indicator lesions
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to progression on combined HerChemo (TTPHerChemo) | 8 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Time to first progression | 8 weeks |
| Time to treatment failure | 8 weeks |
| Overall survival | 8 weeks |
| Response rate | 8 weeks |
| Predictive value of serum HER2/neu ECD levels on clinical outcome | 8 weeks |
| Conversion rate of estrogen receptor status | 8 weeks |
| Association of immunoprofiles of erbB-1, erbB-2, erbB-3 and erbB-4 with clinical outcome | 8 weeks |
| Adverse events | 8 weeks |
Countries
Italy, Switzerland
Outcome results
None listed