Caelyx as Primary Treatment for Patients With Breast Cancer and a History of Heart Disease and/or Age Over 65 Years

Study Overview
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Brief Summary
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This is a multicenter study of a primary chemotherapy regimen in breast cancer patients at risk of developing cardiotoxicity. The aim of the study is to evaluate the response rate at surgery.

Detailed Description
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This is a phase II, uncontrolled, open label, multicenter study of a primary chemotherapy regimen consisting of four cycles of liposomal pegylated doxorubicine 35 mg/m² IV plus cyclophosphamide 600 mg/m² on Day 1 every 4 weeks followed by paclitaxel 80 mg/m²/week for 12 weeks before surgery in breast cancer patients at risk of developing anthracycline-induced cardiotoxicity. Surgery (tumorectomy, quadrantectomy, or mastectomy plus lymphadenectomy) will be performed 2 to 5 weeks after the last primary chemotherapy infusion. Patients with > 10% of hormone receptor-positive cells will receive appropriate hormone therapy according to menopausal status. Patients treated with breast-conserving surgery will receive radiation therapy to the mammary gland. Patients with T4 tumors or significant axillary involvement (≥ ypN2) will receive radiation therapy to the breast or chest wall and to the lymph node chains.

Official Title
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A Phase II, Open-Label, Multicenter Clinical Trial of Pegylated Liposomal Doxorubicin (Caelyx®) as Primary Treatment for Patients With Breast Cancer and a History of Heart Disease or Age Over 65 Years.

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Liposomal pegylated doxorubicine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed invasive breast cancer (tumor > 2 cm). Estrogen receptor-negative or -weakly positive tumors (less than 50% of cells), as evaluated using IHC. Risk factors for developing anthracycline-induced cardiomyopathy. Exclusion Criteria: Severe heart failure (NYHA Class III or IV) . Metastatic disease. LVEF < 45%. Pregnant or breast-feeding patients.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Primary chemotherapy regimen consisting of four cycles of pegylated-liposomal doxorubicine at 35 mg/m² IV plus CPM 600 mg/m² on Day 1 every 4 weeks followed by paclitaxel 80 mg/m²/week for 12 weeks before surgery. | Drug: Liposomal pegylated doxorubicine<br>* Four cycles of liposomal pegylated doxorubicine at 35 mg/m² IV combined with cyclophosphamide at 600 mg/m² on Day 1 every 4 weeks, and followed by paclitaxel 80 mg/m²/week for 12 weeks before surgery.<br>* Other names: Caelyx;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete response (pCR). pCR is defined as the absence of invasive cancer in the surgical breast specimen. This definition includes evidence of carcinoma in situ only. |  | At surgery. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response rate (complete plus partial responses). Clinical response will be assessed by imaging using the WHO criteria. |  | Before and after treatment with paclitaxel. | 
| Breast-conserving surgery: tumorectomy or quadrantectomy with or without lymphadenectomy versus mastectomy. |  | At surgery. | 
| Axillary node involvement after primary chemotherapy. |  | At surgery. | 
| Left ventricular ejection fraction measured by echocardiography or MUGA. |  | At baseline, every 2 doxorubicine cycles and before surgery. | 
| Cardiac sign/symptom questionnaire. |  | At baseline, every 2 doxorubicine cycles and before surgery. | 
| Relapse-free survival at 5 years after surgery and overall survival at 5 years after study entry. |  | Until 5 years after surgery. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast, Cancer, Anthracyclines, Cardiopathy