Study With Docetaxel, Carboplatin and Herceptin Versus Vinorelbine and Herceptin in HER-2 (+) Metastatic Breast Cancer Patients

Study Overview
=================
Brief Summary
-----------------
This trial will compare the efficacy of sequential administration of Docetaxel, Carboplatin and Herceptin versus the administration of Vinorelbine and Herceptin combination as first line treatment in HER-2 positive patients with metastatic breast cancer.

Detailed Description
-----------------
Herceptin, a humanized monoclonal antibody directed against the extracellular domain of the transmembrane glycoprotein HER2/neu (c-erbB-2), is a valuable option in the treatment of women with HER2-positive metastatic breast cancer. The combination of Herceptin and chemotherapy yielded significantly better results than chemotherapy alone in response, time to progression, and survival time. Whether the combination of Docetaxel, Carboplatin and Herceptin versus the administration of Vinorelbine and Herceptin combination in HER-2 positive patients with metastatic breast cancer is preferable is not yet known.

Official Title
-----------------
A Multicenter Randomized Phase II Study of First Line Treatment With Sequential Administration of Docetaxel, Carboplatin and Herceptin Versus the Administration of Vinorelbine and Herceptin Combination in HER-2 Positive Patients With Metastatic Breast Cancer

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

Intervention / Treatment
-----------------
* Drug: Docetaxel
* Drug: Carboplatin
* Drug: Herceptin
* Drug: Vinorelbine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Performance status (WHO) 0-2 Histologically confirmed metastatic breast adenocarcinoma (stage IV) without any prior chemotherapy received HER-2 overexpression 2+ or 3+ using IHC or FISH + Measurable disease not in a prior irradiation field (no other concurrent chemotherapy agents) No more than 25% of myeloproductive bone marrow irradiated (more than 4 weeks since prior radiotherapy and recovered) More than 6 months since prior adjuvant or neoadjuvant chemotherapy and recovered No prior first line chemotherapy for metastatic disease Endocrine therapy is allowed as adjuvant or first line treatment for metastatic disease Paraffin block from the primary tumor available in the research lab Adequate bone marrow function (absolute neutrophil count > 1000/mm^3, platelet count > 100000/mm^3, hemoglobin > 9 gr/mm^3) Adequate liver (Bilirubin < 1.5 times upper limit of normal and SGOT/SGPT < 2 times upper limit of normal) and renal function (creatinine < 2mg/dl) Adequate cardiac function (LVEF > 50%) Informed consent Exclusion Criteria: Pregnant or nursing Concurrent agents ketoconazole, macrolide antibiotics, zidovudine which may induce P-450 cytochrome Positive pregnancy test Motor or sensory neuropathy > grade 1 according to NCIC Τoxicity Criteria Patients with brain metastatic disease who has not been irradiated or uncontrolled brain metastatic disease after irradiation History of allergic reaction attributed to docetaxel Psychiatric illness or social situation that would preclude study compliance Other concurrent uncontrolled illness. Other invasive malignancy within the past 5 years except cured basal cell skin carcinoma and cervical carcinoma in situ

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Docetaxel + Carboplatin + Herceptin (D/Carbo/Her) | Drug: Docetaxel<br>* Docetaxel at the dose of 75mg/m^2 IV on day 1 every 3 weeks for 6 consecutive cycles<br>* Other names: Taxotere;Drug: Carboplatin<br>* Carboplatin at the dose of 5 AUC IV on day 1 every 3 weeks for 6 consecutive cycles<br>Drug: Herceptin<br>* Herceptin 8 mg/Kg on day 1 for the first cycle and 6 mg/Kg for the 5 remaining cycles, IV, every 3 weeks<br>|
| Experimental: 2<br>Vinorelbine + Herceptin (VHer) | Drug: Herceptin<br>* Herceptin 8 mg/Kg on day 1 for the first cycle and 6 mg/Kg for the 5 remaining cycles, IV, every 3 weeks<br>Drug: Vinorelbine<br>* Vinorelbine at the dose of 60mg/m^2 per os,weekly<br>* Other names: Navelbine;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression between the two treatment arms |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 1 year | 
| Toxicity profile |  | During the time of chemotherpy | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cancer, Breast cancer, First line treatment, Docetaxel, Carboplatin, Herceptin, Vinorelbine