Breast Cancer
Conditions
Keywords
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
Brief summary
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
end-point Efficacy: event-free survival (EFS)
Interventions
DRUGZD6474 (Vandetanib at the dose of 100 mg)
100 mg as a once daily oral dose, from Day 1 UNTIL disease progression or unacceptable toxicity or consent withdrawal whichever occurs first
DRUGPlacebo to match ZD6474 (Vandetanib at the dose of 100 mg)
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
DRUGFulvestrant
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.
DRUGZD6474 (Vandetanib at the dose of 300 mg)
300 mg as a once daily oral dose, from Day 1 UNTIL disease progression or unacceptable toxicity or consent withdrawal whichever occurs first.
DRUGPlacebo to match ZD6474 (Vandetanib at the dose of 300 mg)
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
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
45 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event Free Survival | 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. | Success rate (patients without progression and still on treatment at 24 weeks |
Secondary
| Measure | 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. |
Countries
Italy
Participant flow
Recruitment details
The study was prematurely terminated.
Pre-assignment details
39 participants were randomized to receive vandetanib or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Vandetanib at the Dose of 100 mg 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) | 16 |
| Vandetanib at the Dose of 300 mg 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) | 12 |
| Placebo to Match Vandetanib 100 mg and 300 mg 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). | 11 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Protocol Violation | 3 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 2 |
Baseline characteristics
| Characteristic | Vandetanib at the Dose of 100 mg | Vandetanib at the Dose of 300 mg | Placebo to Match Vandetanib 100 mg and 300 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 63.6 years | 59.8 years | 59.6 years | 61.3 years |
| Sex: Female, Male Female | 16 Participants | 12 Participants | 11 Participants | 39 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 16 | 11 / 12 | 6 / 11 |
| serious Total, serious adverse events | 3 / 16 | 2 / 12 | 1 / 11 |
Outcome results
Primary
Event Free Survival
Success rate (patients without progression and still on treatment at 24 weeks
Time frame: 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
Incidence and Type of Adverse Events (AEs), Clinically Significant Laboratory or Vital Sign Abnormalities and Electrocardiographic (ECG) Changes
Time frame: Continuous assessment of safety.
Secondary
Overall Survival
Time frame: Assessments for survival must be made at the 60 day follow-up visit and then every 3 months, unless the patient withdraws consent.
Secondary
Time-To-Progression, Progression-Free Survival, Objective Tumor Response Rate (CR+PR), Disease Control Rate (CR+PR+SD) and Duration of Response (DOR)
Time frame: 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.