Hormone sensitive (ER+ve and/ or PR +ve) advanced breast cancer (ABC)
Conditions
Interventions
Product Name: ZACTIMA
Product Code: ZD6474
Pharmaceutical Form: Tablet
INN or Proposed INN: vandetanib
Current Sponsor code: ZD6474
Concentration unit: mg milligram(s)
Concentration type: equal
Conce
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent 2. Post menopausal females aged 18 years or older Post menopausal defined as patients with: - Natural menopause with menses>1 year ago - Radiation induced oophorectomy with last menses>1 year ago - Chemotherapy induced menopause with last menses>1 year ago - Serum FSH, LH and plasma oestradiol levels in the postmenopausal range for the institution - Bilateral oophorectomy 3. Females with histological/cytological confirmation of breast cancer 4. Patients fulfilling one of the following criteria: a) At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumours (RECIST) b) Patients with bone lesions, lytic or mixed (lytic + sclerotic), in the absence of measurable disease (as defined by RECIST). 5. Hormone sensitive (ER+ and/or PgR+) patients whose disease has progressed either on or within 1 year of adjuvant therapy, or who has progressed on or following first line therapy for advanced disease (excluding aromatase inhibitors) 6. WHO performance status (PS) 0-2 and life expectancy > 12 weeks. Patients with PS 3 will be eligible unless the Investigator believes the poor PS is predominantly due to co-existing morbidity (e.g. severe cardiac impairment) 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. Treatment within 4 weeks before randomisation and/or whilst on study, treatment with the following: Non-approved or experimental drug; Chemotherapy, radiotherapy or other anticancer therapy 2. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site) 3. Previous enrolment or randomisation of treatment in the present study 4. Previous definitive radiotherapy (e.g. to chest wall) within 6 weeks before randomisation 5. Any unresolved toxicity > CTC grade 2 from previous anticancer therapy 6. History of hypersensitivity to active or inactive excipients of ZD6474, placebo or Arimidex 7. Major surgery within 4 weeks of randomisation, or incompletely healed surgical incision 8. 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). 9. Brain metastases or spinal cord compression, unless treated at least 4 weeks before entry, and stable without steroid treatment for 1 week 10. Any of the following laboratory values: Total bilirubin > 1.5 x ULRR; ALT or AST > 2.5 x ULRR or > 5 x ULRR if judged by the investigator to be related to liver metastases; Serum creatinine >1.5 x ULRR and creatinine clearance =2 within 3 months before entry, or presence of cardiac disease that, in the opinion of the investigator, increases the risk of ventricular arrhythmia. 14. History of arrhythmia (multifocal premature ventricular contractions [PVCs], bigeminy, trigeminy, ventricular tacchycardia, symptomatic or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (CTC grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded. 15. Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age 16. Previous QT prolongation with other medication that required discontinuation of that medication 17. Presence of left bundle branch block (LBBB) 18. QTc with Bazett’s correction unmeasurable or >= 480msec or greater on screening ECG (Note: if patient has QTc interval >= 480msec on screening ECG, the screen ECG may be repeated twice, at least 24 hours apart. The average QTc from the 3 screening ECGs must be 160mmHg or diastolic blood pressure >110mmHg) 22. Currently receiving the following drugs that are potent inducers of CYP P450 3A4 - phenytoin, rifampicin, carbamezapine, phenobarbitone and St Johns Wort
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of ZD6474 in combination with Arimidex in the treatment of ABC using the progression event count methodology.;Secondary Objective: To assess the safety and tolerability of ZD6474 in combination with Arimidex in the treatment of ABC by review of adverse events and laboratory parameters;Primary end point(s): Objective disease progression at the data cut-off date (approximately 8 months after the last patient is randomised), as measured using RECIST criteria Death from any cause | — |
Countries
Hungary, Spain, Sweden
Outcome results
None listed