Study of Arimidex and Radiotherapy Sequencing

Study Overview
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Brief Summary
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The purpose of this study is to compare TGF-β1 change in concomitant with that in sequential Arimidex in postmenopausal women with breast cancer, as measured by the proportion of patients with an elevation of TGF-β1 level at the 4th week after initiation of radiotherapy relative to the pre-treatment baseline.

Official Title
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A Prospective, Randomized, Bi-center Study to Compare the Outcome of Adjuvant Radiotherapy With Concomitant or Sequential Arimidex in Postmenopausal Women With Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Pre-radiotherapy commencement of Arimidex
* Drug: Post radiotherapy commencement of Arimidex
* Radiation: Radiotherapy
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent Pathological confirmation of breast cancer ER(+) and/or PR(+). Post-menopausal woman Age≤70 years old Breast conservative surgery with axillary dissection or staging by either sentinel nodes biopsy or axillary sampling Post-mastectomy patients with T1-T2 and N1-N3, or T3-T4 with any N Negative surgical margins Karnofsky≥70 Laboratory criteria: PLT≥100*109/L WBC≥4000/mm3 HGB≥10g/dl ALT and AST<2*ULN No presence of metastatic disease No other malignant tumour Exclusion Criteria: Presence of metastatic disease. T1, T2, N0 with mastectomy Non-infiltrative breast carcinoma underwent mastectomy Other malignant tumor (concurrent or previous). Positive surgical margins. Patients with demonstrated hypersensitivity to Arimidex or any excipient. Patients with severe renal impairment (creatinine clearance less than 20 ml/min). Patients with moderate or severe hepatic disease. Oestrogen-containing therapies should not be co-administered with Arimidex as they would negate its pharmacological action. Not able or willing to sign informed consent Autoimmune diseases including scleroderma, systemic lupus erythematosus and so on

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Study Arm<br>Investigational treatment: Arimidex commenced before and continued during radiotherapy. Interventions: Drug: Pre-radiotherapy commencement of Arimidex Radiation: Radiotherapy | Drug: Pre-radiotherapy commencement of Arimidex<br>* Arimidex:1mg P.O. daily will be prescribed for 8 weeks in post-mastectomy patients and 9 weeks in BCT patients within the study period. Arimidex starts 3 weeks before adjuvant radiotherapy and throughout the course of radiotherapy.Total duration of adjuvant hormonotherapy is prescribed by the investigators at the completion of study, 5 years in principle.<br>* Other names: Anastrozole;Radiation: Radiotherapy<br>* Radiotherapy is delivered to the whole breast/chest wall +/- regional lymph nodes to a total dose of 50Gy/25 fractions/5weeks, an additional tumor bed boost of 10Gy/5 fractions/1week is delivered to patients with breast conservative surgery<br>* Other names: RT, Radiation Therapy;|
| Active Comparator: Control Arm<br>Standard Treatment: Arimidex delayed until 2 weeks after radiotherapy Interventions: Radiation: Radiotherapy Drug: Post radiotherapy commencement of Arimidex | Drug: Post radiotherapy commencement of Arimidex<br>* Arimidex：1mg P.O. daily will be prescribed at 2 weeks after the end of radiotherapy.Total duration of adjuvant hormonotherapy is prescribed by the investigators at the completion of study, 5 years in principle.<br>* Other names: Anastrozole;Radiation: Radiotherapy<br>* Radiotherapy is delivered to the whole breast/chest wall +/- regional lymph nodes to a total dose of 50Gy/25 fractions/5weeks, an additional tumor bed boost of 10Gy/5 fractions/1week is delivered to patients with breast conservative surgery<br>* Other names: RT, Radiation Therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of TGF-β1 | To compare TGF-β1 change in concomitant with that in sequential Arimidex in postmenopausal women with breast cancer, as measured by the proportion of patients with an elevation of TGF-β1 level at the 4th week after initiation of radiotherapy relative to the pre-treatment baseline. | First analysis will occur 1 year after first subject enrolled | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute skin reaction | Acute skin reaction occurrence rate defined by the occurrence of grade II or above acute skin reaction in patients with concurrent or sequential arimidex with radiotherapy. | First analysis will occur 1 year after first subject enrolled | 
| Other serum inflammatory cytokine | Pre-and post-radiotherapy other serum inflammatory cytokine | First analysis will occur 1 year after first subject enrolled | 
| Cosmetic outcomes | Cosmetic outcomes in patients receiving breast conservative therapy treated by both arms. | First analysis will occur 1 year after first subject enrolled | 
| Lung toxicity | Occurrence of grade II or higher radiation-induced lung toxicity. | First analysis will occur 1 year after first subject enrolled | 
| Local-regional recurrence | Local-regional recurrence within two arms. | First analysis will occur 1 year after first subject enrolled | 
| Correlation between TGF-β1 Change and Clinical Outcomes | The correlation between TGF-β1 change and clinical outcomes will be explored. | First analysis will occur 1 year after first subject enrolled | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Timing of Radiotherapy, TGF-beta1