Herceptin Followed by Chemotherapy in Treating Women With Metastatic Breast Cancer That Overexpresses HER2

Study Overview
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Brief Summary
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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
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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.

Official Title
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Randomized Phase III Trial of Herceptin® Followed by Chemotherapy Plus Herceptin® Versus the Combination of Herceptin® and Chemotherapy as Palliative Treatment in Patients With HER2- Overexpressing Advanced/Metastatic Breast Cancer.

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Herceptin™ (Her)
* Drug: Herceptin™ (Her) + chemo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Herceptin™ (Her)<br>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 | Drug: Herceptin™ (Her)<br>* 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<br>|
| Active Comparator: Herceptin™+Chemo<br>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 | Drug: Herceptin™ (Her) + chemo<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression on combined HerChemo (TTPHerChemo) |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate |  | 8 weeks | 
| Time to first progression |  | 8 weeks | 
| Time to treatment failure |  | 8 weeks | 
| Overall survival |  | 8 weeks | 
| Adverse events |  | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent breast cancer, stage IV breast cancer