Caelyx, Cyclophosphamide and Herceptin in Patients With Metastatic Breast Cancer

Study Overview
=================
Brief Summary
-----------------
Eligible patients must receive Caelyx plus Cyclophosphamide plus Herceptin for 6 cycles that will be administered every 4 weeks.

Detailed Description
-----------------
Sample size calculation will be done by means of Simon's method in 2 stages for phase II studies and will be based on the principal aim of the study (evaluation of the rate of objective response). The hypothesis brings over of the efficiency of the treatment it will be accepted if a rate of objective response of at least 55 % is obtained, rejecting the efficiency of the treatment when the rate of response targets be lower than 35 %. In this case, considering an alpha error of 0.05 and 80 % power, 14 patients will be included in the first stage; the study would continue if more than 5 objective responses were found. The total number of patients to including in the study would be 44. The results will be significant if they find at least 20 objective responses. Assuming a drop-out rate of 10 %, the total number of patients needed is 49 patients.

Official Title
-----------------
Phase IV/II Trial With the Combination of Pegylated Liposomal Doxorubicin (Caelyx), Cyclophosphamide and Trastuzumab in Patients With Metastatic Breast Cancer With Overexpression of Human Epidermal Growth Factor Receptor 2 (HER2)/Neu

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: Liposomal Doxorubicin
* Drug: Cyclophosphamide
* Drug: Trastuzumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must sign an informed consent before of specific procedures of clinical trial. Patients with histologically confirmed breast cancer and overexpression of Her2neu. Age> 18 years. Eastern Cooperative Oncology Group (ECOG) equal or < 2. Patients have not been treated previously with chemotherapy for metastatic disease. Patients must have at least one measurable lesion according to RECIST criteria. Patients should have an adequate organ function to tolerate chemotherapy. Exclusion Criteria: Patients with hypersensitivity reactions to any of the medications of the clinical trial. Patients who are pregnant or lactating are not eligible. Hepatic disease. Not controlled active infection Symptomatic metastatic brain cancer Previous adjuvant treatment with anthracyclines with a total accumulated dose > 300 mg/m2 (Doxorubicin) or > 600 mg/m2 (Epirubicin)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Caelyx,Cyclophosphamide,Trastuzumab<br>Caelyx (Liposomal Doxorubicin) 50 mg/m2 every 4 weeks for 6 cycles, Cyclophosphamide 600 mg/m2 every 4 weeks for 6 cycles, Trastuzumab weekly for 24 weeks, at dose of 2mg/kg (day 1 loading dose of 4mg/kg) | Drug: Liposomal Doxorubicin<br> <br> * Other names: Caelyx;Drug: Cyclophosphamide<br> <br> * Other names: Cytoxan;Drug: Trastuzumab<br> <br> * Other names: Herceptin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR is the sum of the Complete Responses (CR) and Partial Responses (PR) according to the RECIST criteria, experienced for each patient during treatment (recorded from the start of the treatment until disease progression). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan (computed tomography) or MRI (magnetic resonance imaging): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response Rate (ORR) = CR + PR. | Up to cycle 6 (24 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression (TTP) | TTP was defined as the time elapsed from first treatment until clinical evidence of disease progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions | Through study treatment, and follow up period, assessed up to 88 weeks | 
| Time to Treatment Failure (TTF) | TTF was defined as the time elapsed from first treatment until patient discontinuation due to toxicity, disease progression, death or withdrawal of consent for any reason, whichever occurred first. | Through study treatment, and follow up period, assessed up to 88 weeks | 
| Response Duration | Response duration was defined as the time elapsed from the first evidence of tumor response (Complete response or Partial Response) until clinical evidence of disease progression or death occurred. | Through study treatment, and follow up period, assessed up to 88 weeks | 
| Overall Survival (OS) | OS was defined as the time elapsed from first treatment until death from any cause. | Through study treatment, and follow up period, assessed up to 88 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HER2 positive breast cancer, Metastatic breast cancer