Study of Arimidex and Radiotherapy Sequencing

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

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.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Pre-radiotherapy commencement of Arimidex; Radiation: Radiotherapy; Drug: Post radiotherapy commencement of Arimidex

• Study Type: Interventional
• Enrollment (Anticipated): 220
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jiayi Chen, MD; Phone Number: 6602 862164175590

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Cancer Hospital
      • Contact: Jiayi Chen, MD; Phone Number: 6602 862164175590
      • Principal Investigator: Jiayi Chen, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Study Arm; Investigational treatment: Arimidex commenced before and continued during radiotherapy. Interventions: Drug: Pre-radiotherapy commencement of Arimidex Radiation: Radiotherapy	Drug: Pre-radiotherapy commencement of Arimidex; 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.; Other Names: Anastrozole; Radiation: Radiotherapy; 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; Other Names: RT, Radiation Therapy
Active Comparator: Control Arm; Standard Treatment: Arimidex delayed until 2 weeks after radiotherapy Interventions: Radiation: Radiotherapy Drug: Post radiotherapy commencement of Arimidex	Radiation: Radiotherapy; 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; Other Names: RT, Radiation Therapy; Drug: Post radiotherapy commencement of Arimidex; 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.; Other Names: Anastrozole

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fudan University
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Jiayi Chen, MD, The Department of Radiation Oncology, Fudan University Cancer Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Anticipated): December 1, 2014
• Study Completion (Anticipated): July 1, 2015

Study Registration Dates

• First Submitted: July 25, 2011
• First Submitted That Met QC Criteria: July 25, 2011
• First Posted (Estimate): July 26, 2011

Study Record Updates

• Last Update Posted (Estimate): June 25, 2014
• Last Update Submitted That Met QC Criteria: June 24, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Breast Cancer; Timing of Radiotherapy; TGF-beta1
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Anastrozole
• Other Study ID Numbers: BR-RT-002