Patients With Advanced Ovarian Cancer Sensitive to Platinum-based Chemotherapy
Conditions
Keywords
ovarian, cancer, chemotherapy, sensitive, ZD4054
Brief summary
The purpose of this study is to compare progression-free survival in patients with advanced ovarian cancer treated with ZD4054 in combination with carboplatin+paclitaxel versus placebo in combination with carboplatin+paclitaxel.
Interventions
DRUGZD4054 Zibotentan
10 mg oral tablets once daily
DRUGPaclitaxel
175mg/m2 IV on day 1 every 3 weeks
DRUGCarboplatin
Carboplatin AUC of 5.0 IV on day 1 every 3 weeks
DRUGPlacebo
matching placebo for ZD4054 10 mg
Sponsors
ISTITUTO REGINA ELENA - CENTRO RICERCHE SPERIMENTALI
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically proven diagnosis of: - Epithelial ovarian carcinoma - Fallopian tube carcinoma - Primary serous peritoneal carcinoma * Radiologically documented measurable disease according to RECIST criteria assessed by Computerised Tomography (CT) or Magnetic Resonance Imaging MRI) or radiologically documented non-measurable (but evaluable) disease. * Advanced disease not amenable to curative surgery or radiotherapy at the time of study entry with evidence of disease recurrence or progression at least 6 months following treatment cessation of first-line platinum- containing therapy
Exclusion criteria
* Clinical evidence of central nervous system (CNS) metastases * Non-epithelial ovarian cancer, including malignant mixed Mullerian tumours and mucinous carcinoma of the peritoneum * Tumour of borderline malignancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Patients were followed for progression up to 2 years | Median time (in months) from randomisation until clinical progression of disease using the Kaplan-Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Patients were followed for survival up to 2 years | Median time (in months) from randomisation until death using the Kaplan-Meier method. |
| Tumour Response Rate | While receiving paclitaxel + carboplatin study visits were aliged with its administration ie every 3 weeks, then every 6 weeks (up to 2 years) | Objective response rate defined as participants with a complete or partial response according to RECIST |
Countries
Germany, Italy
Participant flow
Recruitment details
132 patients with advanced ovarian cancer sensitive to platinum-based chemotherapy were recruited between 26th June 2009 and 1st June 2011.
Pre-assignment details
12 of the 132 enrolled patients were not randomised to treatment groups as they failed screening
Participants by arm
| Arm | Count |
|---|---|
| ZD4054+Paclitaxel+Carboplatin ZD4054 10mg oral tablet once daily + paclitaxel +carboplatin intravenous infusions every 3 weeks | 59 |
| Placebo+Paclitaxel+Carboplatin Placebo oral tablet once daily + paclitaxel +carboplatin intravenous infusions every 3 weeks | 61 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 5 |
| Overall Study | Other termination reason | 5 | 6 |
| Overall Study | Protocol Violation | 32 | 30 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | ZD4054+Paclitaxel+Carboplatin | Placebo+Paclitaxel+Carboplatin | Total |
|---|---|---|---|
| Age Continuous Overall | 57.4 Years STANDARD_DEVIATION 11.98 | 56.6 Years STANDARD_DEVIATION 11.07 | 57.0 Years STANDARD_DEVIATION 11.49 |
| Sex: Female, Male Female | 59 Participants | 61 Participants | 120 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 57 / 58 | 58 / 58 |
| serious Total, serious adverse events | 19 / 58 | 13 / 58 |
Outcome results
Primary
Progression Free Survival
Median time (in months) from randomisation until clinical progression of disease using the Kaplan-Meier method.
Time frame: Patients were followed for progression up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ZD4054+Paclitaxel+Carboplatin | Progression Free Survival | 7.6 Months |
| Placebo+Paclitaxel+Carboplatin | Progression Free Survival | 10.0 Months |
Secondary
Overall Survival
Median time (in months) from randomisation until death using the Kaplan-Meier method.
Time frame: Patients were followed for survival up to 2 years
Population: Overall Survival was not analysed as the study was terminated early.
Secondary
Tumour Response Rate
Objective response rate defined as participants with a complete or partial response according to RECIST
Time frame: While receiving paclitaxel + carboplatin study visits were aliged with its administration ie every 3 weeks, then every 6 weeks (up to 2 years)
Population: The number of participants for analysis corresponds to patients with measurable disease at study entry
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZD4054+Paclitaxel+Carboplatin | Tumour Response Rate | 21 Participants |
| Placebo+Paclitaxel+Carboplatin | Tumour Response Rate | 34 Participants |