ZACtima FASlodex Trial in Postmenopausal Advance Breast Cancer Patients Instead of ZACtima FASlodex Trial

Study Overview
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Brief Summary
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The primary objective is to assess the event-free survival defined as the time from randomisation to progression, death without progression, loss to follow up, whichever occurred first..

Detailed Description
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end-point Efficacy: event-free survival (EFS)

Official Title
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A Randomized,Double-blind,Parallel-group,Multicentre,Phase II Study to Evaluate the Safety and Pharmacological Activity of the Combination of Vandetanib (100 or 300 MG/Daily or Placebo)With Fulvestrant (Loading Dose)in Postmenopausal Advanced BC Patients

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: ZD6474 (Vandetanib at the dose of 100 mg)
* Drug: Placebo to match ZD6474 (Vandetanib at the dose of 100 mg)
* Drug: Fulvestrant
* Drug: ZD6474 (Vandetanib at the dose of 300 mg)
* Drug: Placebo to match ZD6474 (Vandetanib at the dose of 300 mg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Post menopausal women with locally advanced or metastatic breast cancer Patients may have either measurable or non-measurable disease, as defined by RECIST criteria One previous hormone therapy or one previous chemotherapy for advanced disease are allowed (patients who have stable but evident disease after chemotherapy are eligible) estrogen receptor positive ER+ and/or progesterone receptor positive PR+ on primary or secondary tumour Exclusion Criteria: Hormone receptor negative tumours (ER and PR negative) Presence of life-threatening metastatic visceral disease Significant cardiovascular event (e.g. myocardial infarction, superior vena cava [SVC] syndrome, New York Heart Association [NYHA] classification of heart disease ³2) within 3 months before entry, or presence of cardiac disease that in the opinion of History of arrhythmia or QTc with Bazett's correction unmeasurable or ≥ 480 msec on screening ECG

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vandetanib at the dose of 100 mg<br>vandetanib at the dose of 100 mg orally once-daily plus placebo to match vandetanib 300 mg orally once-daily plus fulvestrant LD (500 mg im. at day 1 and 250 mg at day 14, 28 and thereafter every 28th day +/- 3) | Drug: ZD6474 (Vandetanib at the dose of 100 mg)<br>* 100 mg as a once daily oral dose, from Day 1 UNTIL disease progression or unacceptable toxicity or consent withdrawal whichever occurs first<br>* Other names: Zactima;Drug: Fulvestrant<br>* All patients will receive fulvestrant Loading Dose (LD). The Loading Dose regimen is 500mg (2 injections) at day 1, followed by 250mg at day 14, 28 and every 28 days thereafter.<br>* Other names: Faslodex;Drug: Placebo to match ZD6474 (Vandetanib at the dose of 300 mg)<br>* Placebo of 100 mg as a once daily oral dose, from Day 1 UNTIL disease progression or unacceptable toxicity or consent withdrawal whichever occurs first<br>|
| Experimental: Vandetanib at the dose of 300 mg<br>vandetanib at the dose of 300 mg orally once-daily plus placebo to match vandetanib 100 mg orally once-daily plus fulvestrant LD (500 mg im. at day 1 and 250 mg at day 14, 28 and thereafter every 28th day +/- 3) | Drug: Placebo to match ZD6474 (Vandetanib at the dose of 100 mg)<br>* Placebo of 300 mg as a once daily oral dose, from Day 1 UNTIL disease progression or unacceptable toxicity or consent withdrawal whichever occurs first<br>Drug: Fulvestrant<br>* All patients will receive fulvestrant Loading Dose (LD). The Loading Dose regimen is 500mg (2 injections) at day 1, followed by 250mg at day 14, 28 and every 28 days thereafter.<br>* Other names: Faslodex;Drug: ZD6474 (Vandetanib at the dose of 300 mg)<br>* 300 mg as a once daily oral dose, from Day 1 UNTIL disease progression or unacceptable toxicity or consent withdrawal whichever occurs first.<br>* Other names: Zactima;|
| Placebo Comparator: Placebo to match vandetanib 100 mg and 300 mg<br>placebo to match vandetanib 100 mg orally once-daily plus placebo to match vandetanib 300 mg orally once-daily plus fulvestrant LD (500 mg im. at day 1 and 250 mg at day 14, 28 and thereafter every 28th day +/- 3). | Drug: Placebo to match ZD6474 (Vandetanib at the dose of 100 mg)<br>* Placebo of 300 mg as a once daily oral dose, from Day 1 UNTIL disease progression or unacceptable toxicity or consent withdrawal whichever occurs first<br>Drug: Fulvestrant<br>* All patients will receive fulvestrant Loading Dose (LD). The Loading Dose regimen is 500mg (2 injections) at day 1, followed by 250mg at day 14, 28 and every 28 days thereafter.<br>* Other names: Faslodex;Drug: Placebo to match ZD6474 (Vandetanib at the dose of 300 mg)<br>* Placebo of 100 mg as a once daily oral dose, from Day 1 UNTIL disease progression or unacceptable toxicity or consent withdrawal whichever occurs first<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event Free Survival | Success rate (patients without progression and still on treatment at 24 weeks | Restaging (RECIST) is carried out at screening and every 3 months during the study until 1 year and than every 6 months until objective disease progression. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-To-Progression, Progression-Free Survival, Objective Tumor Response Rate (CR+PR), Disease Control Rate (CR+PR+SD) and Duration of Response (DOR) |  | Restaging (RECIST) is carried out at screening and every 3 months during the study until 1 year and than every 6 months until objective disease progression. | 
| Overall Survival |  | Assessments for survival must be made at the 60 day follow-up visit and then every 3 months, unless the patient withdraws consent. | 
| Incidence and Type of Adverse Events (AEs), Clinically Significant Laboratory or Vital Sign Abnormalities and Electrocardiographic (ECG) Changes |  | Continuous assessment of safety. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ZD6474, Vandetanib, Zactima, Fulvestrant, Faslodex, Breast Cancer, Advanced, Metastatic, Hormone Receptor Positive, Post-Menopausal Patients, post-menopausal women with hormone receptor positive advanced breast cancer