A phase II, double-blind, placebo controlled, randomised study to assess the efficacy and safety of ZD6474 in combination with docetaxel (Taxotere) vs docetaxel alone as 2nd line treatment for advanced breast cancer (ABC)

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-003592-20-SE
• Date of registration: 04/10/2005
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: A phase II, double-blind, placebo controlled, randomised study to assess the efficacy and safety of ZD6474 in combination with docetaxel (Taxotere) vs docetaxel alone as 2nd line treatment for advanced breast cancer (ABC)
• Scientific title: A phase II, double-blind, placebo controlled, randomised study to assess the efficacy and safety of ZD6474 in combination with docetaxel (Taxotere) vs docetaxel alone as 2nd line treatment for advanced breast cancer (ABC)
• Date of first enrolment: 05/01/2006
• Target sample size: 65
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-003592-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Hungary, Spain, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provision of informed consent

2. Female patients aged 18 years or older

3. Females with histological/cytological confirmation of breast cancer

4. Patients with at least one evaluable (measurable and/or non-measurable) lesion

5. Patients fulfilling one of the following criteria:
(a) Patients should have immunochemistry confirmed receptor negative breast cancer
(b) Patients who have failed hormonal treatment and who are only eligible for cytotoxic therapy
(c) Patients for whom the investigator considers hormonal treatment unsuitable and thus are only eligible for cytotoxic therapy


6. Patients fulfilling one of the following criteria:
(a) Patients that have failed either on or within 1 year of adjuvant therapy excluding taxanes
(b) Patients that have progressed on or following first line therapy for advanced disease excluding taxanes provided they did not receive a taxane containing adjuvant regimen in the last 12 months.
(c) Patients that have failed more than 1 year after a taxane containing adjuvant regimen and subsequently have progressed on or following a non-taxane containing first line therapy


7. WHO performance status (PS) 0 to2 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)

8. Negative pregnancy test for women of child-bearing potential

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:
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 other than hormonal therapy
Treatment with a hormonal anti-cancer agent within 2 weeks before randomisation and/or whilst on study.

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 > Common Toxicity Criteria (CTC) grade 2 from previous anticancer therapy

6. History of hypersensitivity to active or inactive excipients of ZD6474, placebo or docetaxel

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: Serum bilirubin greater than the upper limit of reference range (ULRR); Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 1.5 x ULRR and alkaline phosphatase greater than 2.5 ULRR; Serum creatinine >1.5 x ULRR and creatinine clearance < or =50mL/minute (calculated by Cockcroft-Gault formula)

11. Any of the following laboratory values: platelets <100x10e9/L; absolute neutrophil count (ANC) <1.5 x 10e9/L

12. Potassium <4.0 mmol despite supplementation; serum calcium (or ionised or adjusted for albumin), or magnesium out of normal range despite supplementation

13. Significant cardiac event (e.g. myocardial infarction, superior vena cava syndrome, New York Heart Association classification of heart disease > or =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, bigeminy, trigeminy, ventricular tachycardia, 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

18. QTc with Bazett’s correction unmeasurable or > or =480msec or greater on screening ECG (Note: if patient has QTc interval >or =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 <480msec for the patient to be eligible for the study)

19. Any concomitant medications that may cause QTc prolongation or induce Torsades de Pointes (as defined in the protocol)

20. Any severe concomitant condition which, in the Investigator’s opinion, makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the study protocol e.g. uncontrolled cardiac disease

21. Hyperte

Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Advanced breast cancer (ABC)

Intervention(s)

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
Concentration number: 100-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To assess the safety and tolerability of ZD6474 in combination with docetaxel in the treatment of ABC by review of adverse events and laboratory parameters.

Main Objective: To assess the efficacy of ZD6474 in combination with docetaxel in the treatment of ABC using the progression event count methodology.

Primary end point(s): The primary outcome variable is a progression event defined as the earliest of:
· Objective disease progression at the data cut-off date (approximately 6 months after the last patient is randomised), as measured using RECIST criteria
· Death from any cause

Secondary ID(s)

2005-003592-20-HU

D4200C00046