Postmenopausal women with oestrogen receptor (ER) positive advanced breast cancer who have either relapsed whilst on adjuvant endocrine therapy, or progressed whilst on first endocrine therapy for advanced disease, or who have had recurrent disease within 12 months after completion of adjuvant therapy
Conditions
Interventions
Trade Name: FASLODEX
Product Name: FASLODEX
Product Code: ZD9238
Pharmaceutical Form: Solution for injection
INN or Proposed INN: fulves
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent 2. Histological/cytological confirmation of breast cancer (from either primary or metastatic tumour) 3. Documented positive oestrogen receptor status (ER +ve) of primary or metastatic tumour tissue, defined as =10% positive staining by Immunohistochemistry (IHC) 4. Requiring hormonal treatment: · Relapsing during, or within 12 months of completion of, adjuvant endocrine therapy (tamoxifen, toremifene or aromatase inhibitors such as anastrozole, letrozole and exemestane)*, or · Progressing on an endocrine therapy (tamoxifen, toremifene or aromatase inhibitors such as anastrozole, letrozole and exemestane) provided that this endocrine treatment was started at least 12 months after the completion of adjuvant endocrine treatment, or · Progressing on an endocrine therapy (tamoxifen, toremifene or aromatase inhibitors such as anastrozole, letrozole and exemestane) given as first treatment for patients with de novo advanced breast cancer** *Use of more than one agent in the adjuvant setting is acceptable. **Advanced breast cancer: Metastatic disease or locally advanced disease which is not amenable to treatment with curative intent. 5. Patients with measurable disease as per RECIST criteria. This is defined as at least one targeted lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as = 20 mm with conventional technique or as = 10 mm with spiral CT scan. 6. Postmenopausal women are defined as those women fulfilling any 1 of the following criteria: · Age = 60 years. · Having undergone a bilateral oophorectomy. · Age 12 months prior to randomisation or - Age > 45 years - If they were on an LHRH analogue the last depot must have been administered > 4 months prior to randomisation and FSH and oestradiol levels must be in the post menopausal range. · For patients with at least one intact ovary and prior history of hysterectomy: FSH and oestradiol levels must be in the post menopausal range AND - If they received systemic cytotoxic anti-cancer therapy - The last dose must have been > 12 months prior to randomisation or - Age > 45 years - If they were on an LHRH analogue the last depot must have been administered > 4 months prior to randomisation. 7. WHO performance status 0, 1 or 2. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Presence of life-threatening metastatic visceral disease, defined as extensive hepatic involvement, or any degree of brain or leptomeningeal involvement (past or present), or symptomatic pulmonary lymphangitic spread. Patients with discrete pulmonary parenchymal metastases are eligible, provided their respiratory function is not clinically and significantly compromised as a result of disease. 2. More than one previous regimen of systemic anti-cancer therapy other than endocrine treatment for advanced disease. Note: Patients previously treated with one regimen of systemic anti-cancer therapy other than endocrine treatment for advanced disease are allowed as long as their last treatment is an anti-oestrogen or an aromatase inhibitor 3. More than one previous regimen of endocrine therapy for advanced disease. Note: Oophorectomy, ovarian ablation, or LH-RH analogue therapy do not count as endocrine treatments in this context and also do not render the patient ineligible for this study. 4. Extensive radiation therapy within 4 weeks prior to randomisation (greater than or equal to 30% marrow or whole pelvis or spine) or systemic anti-cancer therapy other than endocrine treatment within 4 weeks prior to randomisation, or radiolabelled strontium (or other radiopharmaceuticals) within 12 weeks prior to randomisation. 5. Treatment with a non-approved or experimental drug except the post-manufacturing/marketing clinical study drug within 4 weeks before randomisation. 6. Current or prior malignancy within previous 3 years (other than breast cancer or adequately treated basal cell or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix). 7. Any of the following laboratory values within 3 weeks prior to randomisation: · Platelets 1.5 ´ ULRR* · ALT or AST > 2.5 ´ ULRR if no demonstrable liver metastases or > 5 ´ ULRR in presence of liver metastases * Patients with confirmed Gilbert’s syndrome may be included in the study 8. History of: · bleeding diathesis (i.e., disseminated intravascular coagulation [DIC], clotting factor deficiency), or · long-term anticoagulant therapy (other than antiplatelet therapy and low dose warfarin – see Section 3.7). 9. History of hypersensitivity to active or inactive excipients of fulvestrant and/or castor oil. 10. Any severe concomitant condition which makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the trial protocol e.g., uncontrolled cardiac disease or uncontrolled diabetes mellitus. 11. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site) 12. Previous enrolment or randomisation of treatment in the present study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the objective response rate (ORR) of patients treated with fulvestrant 250 mg, fulvestrant 250 mg (plus 250 mg loading regimen) and fulvestrant 500 mg.; Secondary Objective: 1. To estimate the pharmacokinetic characteristics of fulvestrant in patients treated with fulvestrant 250 mg, fulvestrant 250 mg (plus 250 mg loading regimen) and fulvestrant 500 mg by measuring Cmax, Clearance and Volume of distribution at steady state. 2. To evaluate the efficacy of fulvestrant 250 mg, fulvestrant 250 mg (plus 250 mg loading regimen) and fulvestrant 500 mg treatment in terms of time to progression (TTP). 3. To evaluate the clinical benefit rate (CBR) of patients treated with fulvestrant 250 mg, fulvestrant 250 mg (plus 250 mg loading regimen) and fulvestrant 500 mg. 4. To evaluate the duration of response (DoR) in patients treated with fulvestrant 250 mg, fulvestrant 250 mg (plus 250 mg loading regimen) and fulvestrant 500 mg. 5. To assess the tolerability of fulvestrant 250 mg, fulvestrant 250 mg (plus 250 mg loading regimen) and fulvestrant 500 mg by adverse events, safety clinical laboratory tests and vital signs, electrocardiogram and physical examination. ; Primary end point(s): Recruitment is expected to be completed by 15th October 2007. The study will be analysed when all patients, except withdrawals, have been followed up for at least 24 weeks. The data will be reviewed in order to allow the continued supply of randomised treatment to those patients receiving clinical benefit. Since in this study the study treatment will be continued until the progression of disease, the occurrence of an intolerable AE, its discontinuation requested by a subject or required for other reasons, or the completion of the whole study, it is difficult to clearly set the time of study completion. For this reason, the comple | — |
Countries
Belgium, Czech Republic, Hungary
Outcome results
None listed