Ovarian Cancer
Conditions
Keywords
Poly(ADP ribose), polymerisation (PARP), Platinum sensitive, Advanced Serous Ovarian cancer, olaparib, PARP inhibitors, Platinum Sensitive Advanced Serous Ovarian Cancer
Brief summary
To compare the efficacy of olaparib in combination with paclitaxel and carboplatin (AUC4) when compared with carboplatin (AUC6) and paclitaxel alone in patients with advanced ovarian cancer.
Interventions
DRUGolaparib
Tablets Oral BID
DRUGpaclitaxel
175mg/m2 iv for 6 cycles (18 weeks) day 1 of 21 day cycle
DRUGcarboplatin
AUC6 iv for 6 cycles (18 weeks) day 1 of 21 day cycle
DRUGDrug: carboplatin
AUC4 iv for up to 6 cycles (18 weeks)
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 125 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with serous ovarian cancer * Patients who have received no more than 3 previous platinum containing treatments and were progression free for at least 6 months following the end of the last platinum treatment * At least one lesion that is suitable for accurate repeated measurements
Exclusion criteria
* Patients receiving any systemic anticancer chemotherapy, radiotherapy (except palliative) within two weeks from the last dose prior to study treatment * Hypersensitivity to pre medications required for treatment with paclitaxel/carboplatin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Radiologic scans performed at weeks 9 and 18 (+/-1 week) and every 12 weeks thereafter relative to the date of randomisation until the primary analysis (approximately 20 months) | PFS (based on independent central review) was defined as the time from randomisation until objective disease progression as defined by Response Evaluation Criteria In Solid Tumours (RECIST) v1.1 (≥20% increase in the sum of the diameters of target lesions from minimum, clinically significant progression in non-target lesions or the presence of a new lesion) or death (by any cause in the absence of progression). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Following disease progression, patients will be contacted every 12 weeks to assess survival status until the final analysis (approximately 50 months) | OS was defined as the time from randomisation until death by any cause. Patients who had not died at the time of analysis were censored at the last date the patient was known to be alive. Updated OS based on final OS analysis (DCO 31 January 2014) |
| Percentage Change in Tumour Size | Week 9 (+/- 1 week) | The total tumour size was defined as the sum of the longest diameters of the target lesions. At week 9, the percentage change in tumour size was calculated as \[(week 9 sum of target lesions - baseline sum of target lesions)/baseline sum of target lesions\]\*100 for each patient. Imputations were used for missing data where possible. |
Countries
Australia, Belgium, Canada, Czechia, Germany, Italy, Japan, Netherlands, Panama, Peru, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORJane Robertson, BSc, MBCHB, MD
AstraZeneca
PRINCIPAL_INVESTIGATORAmit Oza, MD
Princess Margaret Hospital, Canada
Participant flow
Recruitment details
The first patient was enrolled on 12-Feb-2010. The last patient was enrolled on 15-Jul-2010. Patients were enrolled at 43 sites in 12 countries: Australia, Belgium, Canada, Czech Republic, Germany, Italy, Japan, the Netherlands, Panama, Spain, the UK and the USA. 173 patients were screened and 162 patients were enrolled to receive treatment.
Pre-assignment details
Patient randomisation was stratified(using an interactive voice response \[IVR\]system) based on:1) number of prior platinum-containing treatment lines received(1or\>1) and 2)time to disease progression following completion of the previous platinum-containing therapy(\>6to\<=12 months or\>12 months).Six patients in the C6/P arm did not receive treatment.
Participants by arm
| Arm | Count |
|---|---|
| Olaparib/Carboplatin AUC4/Paclitaxel Olaparib orally (po) (200mg bd Days 1-10 of a 21-day cycle) in combination with paclitaxel intravenous (iv) (175 mg/m2 Day 1 of a 21-day cycle) and carboplatin iv (AUC4 Day 1 of a 21-day cycle) for at least 4 cycles.
Followed by olaparib monotherapy maintenance (400mg bd continuous dosing) | 81 |
| Carboplatin AUC6/Paclitaxel Paclitaxel iv (175mg/m2 Day 1 of a 21-day cycle) and carboplatin iv (AUC6 Day 1 of a 21-day cycle) for 6 cycles.
Followed by a post-completion phase in which no study treatment was administered | 81 |
| Total | 162 |
Baseline characteristics
| Characteristic | Olaparib/Carboplatin AUC4/Paclitaxel | Carboplatin AUC6/Paclitaxel | Total |
|---|---|---|---|
| Age, Continuous | 57.9 years STANDARD_DEVIATION 10 | 59.0 years STANDARD_DEVIATION 10.7 | 58.5 years STANDARD_DEVIATION 10.3 |
| Age, Customized < 50 | 15 Participants | 17 Participants | 32 Participants |
| Age, Customized ≥ 50 - < 65 | 45 Participants | 40 Participants | 85 Participants |
| Age, Customized ≥ 65 | 21 Participants | 24 Participants | 45 Participants |
| Classification of BRCA status BRCAm | 20 Participants | 21 Participants | 41 Participants |
| Classification of BRCA status BRCA missing | 27 Participants | 28 Participants | 55 Participants |
| Classification of BRCA status BRCA VUS | 4 Participants | 3 Participants | 7 Participants |
| Classification of BRCA status BRCAwt | 30 Participants | 29 Participants | 59 Participants |
| Number of prior platinum-containing treatment lines 1 | 58 Participants | 53 Participants | 111 Participants |
| Number of prior platinum-containing treatment lines >1 | 23 Participants | 28 Participants | 51 Participants |
| Sex: Female, Male Female | 81 Participants | 81 Participants | 162 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Time to disease progression on completion of the previous platinum therapy PD >12 months after completion | 42 Participants | 41 Participants | 83 Participants |
| Time to disease progression on completion of the previous platinum therapy PD > 6 to ≤ 12 months after completion | 39 Participants | 40 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 54 / 81 | 47 / 81 |
| other Total, other adverse events | 81 / 81 | 72 / 75 |
| serious Total, serious adverse events | 17 / 81 | 19 / 75 |
Outcome results
Primary
Progression Free Survival (PFS)
PFS (based on independent central review) was defined as the time from randomisation until objective disease progression as defined by Response Evaluation Criteria In Solid Tumours (RECIST) v1.1 (≥20% increase in the sum of the diameters of target lesions from minimum, clinically significant progression in non-target lesions or the presence of a new lesion) or death (by any cause in the absence of progression).
Time frame: Radiologic scans performed at weeks 9 and 18 (+/-1 week) and every 12 weeks thereafter relative to the date of randomisation until the primary analysis (approximately 20 months)
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olaparib/Carboplatin AUC4/Paclitaxel | Progression Free Survival (PFS) | 12.2 months |
| Carboplatin AUC6/Paclitaxel | Progression Free Survival (PFS) | 9.6 months |
Comparison: The null hypothesis for all efficacy analyses in this study is that there is no difference in treatment effects between olaparib in combination with carboplatin/paclitaxel compared with carboplatin/paclitaxel alone.p-value: 0.001295% CI: [0.34, 0.77]Log Rank
Secondary
Overall Survival (OS)
OS was defined as the time from randomisation until death by any cause. Patients who had not died at the time of analysis were censored at the last date the patient was known to be alive. Updated OS based on final OS analysis (DCO 31 January 2014)
Time frame: Following disease progression, patients will be contacted every 12 weeks to assess survival status until the final analysis (approximately 50 months)
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olaparib/Carboplatin AUC4/Paclitaxel | Overall Survival (OS) | 54 Participants (Number of deaths) |
| Carboplatin AUC6/Paclitaxel | Overall Survival (OS) | 47 Participants (Number of deaths) |
Comparison: The null hypothesis for all efficacy analyses in this study is that there is no difference in treatment effects between olaparib in combination with carboplatin/paclitaxel compared with carboplatin/paclitaxel alone.p-value: 0.437995% CI: [0.79, 1.73]Log Rank
Secondary
Percentage Change in Tumour Size
The total tumour size was defined as the sum of the longest diameters of the target lesions. At week 9, the percentage change in tumour size was calculated as \[(week 9 sum of target lesions - baseline sum of target lesions)/baseline sum of target lesions\]\*100 for each patient. Imputations were used for missing data where possible.
Time frame: Week 9 (+/- 1 week)
Population: FAS, but including only patients with target lesions at baseline
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Olaparib/Carboplatin AUC4/Paclitaxel | Percentage Change in Tumour Size | -38.4 Percentage change | Standard Error 4 |
| Carboplatin AUC6/Paclitaxel | Percentage Change in Tumour Size | -39.1 Percentage change | Standard Error 4 |