Low-Dose/Metronomic(LDM)Chemotherapy for Metastatic Breast Cancer

Study Overview
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Brief Summary
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Low-dose metronomic(LDM)chemotherapy as well as anti-inflammatory agents and bisphosphonates have shown anti-angiogenic properties on tumor vasculature. This study is meant to test the therapeutic potential of an anti-angiogenic treatment strategy by combining all these agents for metastatic breast cancer patients.

Official Title
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Antiangiogenic Treatment Strategy With Metronomic Chemotherapy Regimen Combined With a Cox-2 Inhibitor and a Bisphosphonate for Patients With Metastatic Breast Cancer

Conditions
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Chemotherapy, Breast Cancer, Metastatic

Intervention / Treatment
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* Drug: Cyclophosphamide, Capecitabine, Methotrexate, Celecoxib, Pamidronate (or Zoledronate)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic proof of infiltrating duct carcinoma of breast. Her-2 negative tumors. ECOG performance status: 0-1. Presence of measurable disease: primary and/or metastatic. CBC showing normal values or any toxicity limited to grade I. SMA showing liver and renal functions < 1.5 normal values previous treatment with an anthracycline and with a taxane is mandatory either as neoadjuvant/adjuvant treatment or for metastatic disease. previous treatment by chemotherapy for metastatic disease is allowed (up to three lines, allowing for MTD Capecitabine to be one of them). previous treatment by a bisphosphonate is allowed. However,those patients who up to the study had not received any bisphosphonate and those who had received Clodronate- will receive Pamidronate; those who had been under Pamidronate- will receive Zoledronate; those who had been under Zoledronate- will continue with it. The patient's signature on the informed consent. Exclusion Criteria: Her-2 neu positive tumor Inability to visit the clinic for outpatient treatment and evaluation Active/symptomatic brain metastases. ECOG performance status: 2-4. Presence of Hand -Foot syndrome, at grade > 2. CBC with any grade >2 toxicity SMA showing liver functions > 1.5 normal values SMA showing renal functions > normal values -Current continuous treatment by steroids or by NSAIDs, or by anti- coagulants for non protocol reasons. presence of exclusively non-measurable disease (I/E: exclusive bone disease with non-representative tumor markers). previous radiotherapy to the only measurable disease. pleural or peritoneal effusion that may represent a third space. history of active peptic ulcer. symptomatic coronary heart disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: intervention<br>same treatment for all patients | Drug: Cyclophosphamide, Capecitabine, Methotrexate, Celecoxib, Pamidronate (or Zoledronate)<br>* Cyclophosphamide Tab. 50mg, 1x1/day, continuously. Capecitabine Tab. 500mg, 1+2/day, continuously. Methotrexate Tab. 2.5mg, 1x2/day, 2 days every week. Celecoxib Tab. 200mg, 1x2/day, continuously. Pamidronate I.V. 90mg, every 4 weeks; or Zoledronate I.V. 4mg, every 4 weeks)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the efficacy by rate of clinical benefit (CB): rate of response (RR) + rate of Stable Disease (SD) |  | 6 and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Levels of angiogenic growth factors |  | At 4 predetermined time points along treatment period. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metronomic chemotherapy, anti-angiogenic effect, Breast cancer