Study in Letrozole Combined With Metronomic Oral Cyclophosphamide in Elderly Metastasis Breast Cancer Patients

Study Overview
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Brief Summary
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This is a randomized clinical trial to investigate the efficacy of letrozole combined with metronomic oral cyclophosphamide in elderly metastasis breast cancer patients.

Conditions
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Breast Neoplasms, Neoplasm Metastasis

Intervention / Treatment
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* Drug: Cyclophosphamide 50mg
* Drug: Letrozole 2.5 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed metastatic breast cancers patients with estrogen receptor positive and/or progesterone receptor positive; Elderly women (age ≥ 65years) Failure or relapse from standard chemotherapy or unfit for chemotherapy Measurable disease per Response Evaluation Criteria in Solid Tumors(RECIST); Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; Adequate bone marrow, liver and renal function; Estimated life expectancy of at least 3 months. Exclusion Criteria: Serious or uncontrolled concurrent medical illness Uncontrolled primary and metastatic brain tumor History of second primary malignancies Having been enrolled in other clinical trials within a month

Ages Eligible for Study
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Minimum Age: 65 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cyclophosphamide alone<br>Patients who were resistant to letrozole will be randomized to receive cyclophosphamide alone or letrozole plus cyclophosphamide. Patients in this arm will receive cyclophosphamide 50 mg daily. | Drug: Cyclophosphamide 50mg<br> <br> |
| Experimental: Cyclophosphamide plus letrozole for resistant patients<br>Patients who were resistant to letrozole will be randomized to receive cyclophosphamide alone or letrozole plus cyclophosphamide. Patients in the this will receive cyclophosphamide 50 mg daily plus letrozole 2.5 mg daily. | Drug: Cyclophosphamide 50mg<br> <br> Drug: Letrozole 2.5 mg<br> <br> |
| Experimental: Cyclophosphamide plus letrozole for treat-naive patients<br>Patients who haven't received letrozole hormonotherapy will be randomized to receive letrozole plus cyclophosphamide or letrozole alone. Patients in this arm will receive cyclophosphamide 50 mg daily plus letrozole 2.5 mg daily. | Drug: Cyclophosphamide 50mg<br> <br> Drug: Letrozole 2.5 mg<br> <br> |
| Active Comparator: letrozole alone<br>Patients who haven't received letrozole hormonotherapy will be randomized to receive letrozole plus cyclophosphamide or letrozole alone. Patients in this arm will receive letrozole 2.5 mg daily. | Drug: Letrozole 2.5 mg<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival(PFS) of the subjects | Time from the randomization date to the start of disease progression or subject death from any cause (progression assessed by investigator using Response Evaluation Criteria in Solid Tumors 1.1for elderly metastatic breast cancer subjects). | up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of each treatment regimen for the subjects | Assessment based on Adverse Events (AEs) , Serious Adverse Events (SAEs), laboratory abnormalities in subjects . | up to approximately 2 years | 
| Evaluate the quality of life for the subjects in the each treatment regimen | Subjects complete questionnaire in every 8 weeks. | up to approximately 2 years | 
| Compare disease control rate for the subjects | Complete response (CR), Partial response (PR), and Stable Disease (SD) more than or equal to 8 weeks. | up to approximately 2 years |