A partially-blind phase III randomised trial of fulvestrant (Faslodex™) with or without concomitant anastrozole (Arimidex™) compared with exemestane in post-menopausal women with oestrogen receptor (ER) positive locally advanced/metastatic breast cancer following progression on non-steroidal aromatase inhibitors

Phase 3

Completed

• Conditions: ocally advanced/metastatic breast cancer; Cancer; Locally advanced/metastatic breast cancer

• Registration Number: ISRCTN44195747
• Lead Sponsor: The Royal Marsden NHS Foundation Trust / The Institute of Cancer Research (UK)

Brief Summary

2013 Results article in http://www.ncbi.nlm.nih.gov/pubmed/23902874 results

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2003-09-08
• Study Completion: 2006-01-01
• Last Update Posted: 8 January 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Female
• Target Recruitment: 698

Inclusion Criteria

Patients with locally advanced/metastatic breast cancer who have progressed on the non-steroidal aromatase inhibitors (Arimidex™ or letrozole [Femara™]):
1. Female postmenopausal patients defined as:
1.1. Aged 60 years or over
1.2. Aged 45 to 59 with intact uterus and amenorrhoeic for at least 12 months
1.3. Any age having had a bilateral oophorectomy
2. Histologically or cytologically confirmed adenocarcinoma of the breast
3. Patients with original ER positive and/or progesterone (PgR) positive breast cancer which has relapsed or progressed during endocrine therapy with a single-agent non-steroidal aromatase inhibitor (NSAI) given either:
3.1. As adjuvant treatment where the patient received at least 12 months therapy, or
3.2. As first-line therapy for metastatic disease. Patients treated with an NSAI as first-line therapy must have had either an objective response (complete response [CR]/partial response [PR]), or stabilisation of disease for at least six months.
4. Measurable/evaluable sites of metastatic disease (response evaluation criteria in solid tumours [RECIST])
5. World Health Organisation (WHO) performance status zero, one or two
6. Prior therapy permissible:
6.1. Tamoxifen given in the adjuvant or neo-adjuvant setting only
6.2. Prior chemotherapy in the adjuvant or neo-adjuvant setting
6.3. Prior chemotherapy as first-line treatment for metastatic breast cancer followed by NSAI alone for at least six months
6.4. Patients with bone-only metastases are eligible provided they have evaluable site of bone metastases that can be followed by skeletal survey or magnetic resonance imaging (MRI)/computed tomography (CT) scanning
6.5. Patients already established on bisphosphonate therapy for at least six months are eligible for the trial and may continue on bisphosphonates
7. Written informed consent and available for prolonged follow-up
8. Adequate haematological function defined by haemoglobin more than or equal to 10 g/dl, neutrophil count more than or equal to 1.5 x 10^9/l and platelets more than or equal to 100 x 10^9/l
9. Adequate hepatic function defined by aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 x upper limit of normal. Alkaline phosphatase less than or equal to 5 x upper limit of normal, unless bone metastases in the absence of liver disease. Renal function adequate defined by creatinine less than 175 mmol/l.
10. Life expectancy of more than three months and suitable for further endocrine therapy

Exclusion Criteria

1. Patients whose primary breast cancer was classified as:
1.1. ER negative and PgR natural killer (NK)
1.2. ER negative/PgR negative
1.3. ER NK
2. Rapidly progressive visceral disease (i.e., lymphangitis carcinomatosa, diffuse hepatic involvement)
3. Bone-only metastases where lesions are not evaluable (i.e., patients with the same scan but no lytic disease on skeletal survey or MRI/CT)
4. Patients with malignancies (other than breast cancer) within the last five years, except for adequately treated in situ carcinoma of the cervix or basal cell/squamous cell carcinoma of the skin
5. Systemic corticosteroids for more than 15 days within the last four weeks
6. Investigational drugs given within the previous four weeks
7. Patients with thrombocytopaenia (platelets less than 100 x 10^9/l ) or on anti-coagulant therapy (contra-indicated due to risk of bleeding with intramuscular injection of Faslodex™)

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Progression-free survival

Secondary Outcome Measures

Name	Time	Method
1. Objective complete response (CR) and partial response (PR) rate<br>2. Duration of response<br>3. Clinical benefit (i.e., six-month CR, PR, and stable disease) rate <br>4. Duration of clinical benefit<br>5. Time to treatment failure<br>6. Overall survival <br>7. Tolerability