Ovarian Neoplasms, Ovarian Cancer
Conditions
Keywords
Cancer, Tumour, Ovarian Neoplasms, Ovarian Cancer
Brief summary
The main purpose of this study is to determine if AZD0530 can improve the efficacy of standard chemotherapy for the treatment of ovarian cancer
Interventions
DRUGAZD0530
oral once daily dose
DRUGCarboplatin
intravenous injection
DRUGPaclitaxel
intravenous infusion
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis of advanced ovarian cancer * Have evidence of recurrence or disease progression at least 6 months following treatment cessation of 1st or 2nd line platinum containing therapy * Estimated life expectancy of more than 12 weeks
Exclusion criteria
* Central Nervous System (CNS) metastases * Received more than 2 prior chemotherapy regimens for ovarian cancer treatment * Inadequate bone marrow reserve * Inadequate liver function, renal function or low haemoglobin * Pregnant, breastfeeding or if of child-bearing status unwilling to use an acceptable method of contraception
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate as Evaluated by Response Evaluation Criteria In Solid Tumors ( RECIST) | Response is evaluated from randomization to objective disease progression per RECIST criteria or death due to any cause in the absence of progression (conducted when a minimum of 78 progression free survival events had occurred) | Number of responders (complete (CR) or partial (PR) responders). CR = disappearance of all target lesions PR = 30% decrease in the sum of the longest diamete. Analysis was based on August 31, 2009 data cut-off , and was performed with patients who had measurable disease and received AZD0530 175mg or Placebo 175mg. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) as Evaluated by RECIST | Date of randomization to earliest date of objective disease progression or death due to any cause (conducted when a minimum of 78 progression free survival events had occurred) | Interval between date of randomization and earliest date of objective disease progression per RECIST criteria or death due to any cause in the absence of progression. Analysis was based on August 31, 2009 data cut-off (78 PFS events analysis) and was performed with patients in ITT analysis set who received AZD0530 175mg or Placebo 175mg. |
| Overall Survival (Number of Deaths) | Date of randomization to death due to any cause | Interval between date of randomization and death due to any cause. Analysis was based on January 31, 2010 data cut-off and was performed with patients in ITT analysis set who received AZD0530 175mg or Placebo 175mg. At this time, data were still immature and median overall survival was not reached. Number of deaths is presented instead |
Countries
Bulgaria, Canada, Denmark, France, Netherlands, Norway, Peru, Portugal, Romania, Russia, Spain, United Kingdom
Participant flow
Recruitment details
Patients were recruited at 58 cancer clinics in 12 countries (Bulgaria, Canada, Denmark, France, Netherlands, Norway, Peru, Portugal, Romania, Russia, Spain and UK) between April 2008 and March 2009.
Pre-assignment details
Following enrolment there was a 28 day screening period, after which if all inclusion/exclusion criteria were met, patients were randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| AZD0530 , Paclitaxel , Carboplatin i.v. AZD0530 175 mg in combination with Carboplatin AUC 6.0 mg/mL/min plus Paclitaxel 175 mg/m2 i.v.; Applies to the group receiving AZD0530 :An initial cohort of patients enrolled in the study were randomised to the 125 mg dose level; once confirmation of the tolerability of AZD0530 175 mg was available from a phase I dose escalation study (D8180C00023), all patients subsequently enrolled were randomised at the 175 mg dose level | 105 |
| Carboplatin ,Paclitaxel Carboplatin AUC 6.0 mg/mL/min, Paclitaxel 175 mg/m2 i.v; | 106 |
| Total | 211 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Death | 12 | 18 |
| Overall Study | Study completion at 120 PFS events | 2 | 2 |
| Overall Study | Withdrawal by Subject | 9 | 3 |
Baseline characteristics
| Characteristic | Carboplatin ,Paclitaxel | AZD0530 , Paclitaxel , Carboplatin i.v. | Total |
|---|---|---|---|
| Age Continuous | 59.1 Years STANDARD_DEVIATION 10.2 | 57.4 Years STANDARD_DEVIATION 9.9 | 58.265 Years STANDARD_DEVIATION 10.077 |
| Body Surface Area (BSA) | 1.766 m^2 STANDARD_DEVIATION 0.206 | 1.758 m^2 STANDARD_DEVIATION 0.17 | 1.762 m^2 STANDARD_DEVIATION 0.189 |
| Primary Tumour Location (Number of Participants) Ovary | 98 Participants | 98 Participants | 196 Participants |
| Primary Tumour Location (Number of Participants) Peritoneum | 5 Participants | 4 Participants | 9 Participants |
| Primary Tumour Location (Number of Participants) Site cannot be determined | 1 Participants | 0 Participants | 1 Participants |
| Primary Tumour Location (Number of Participants) Unavailable | 1 Participants | 0 Participants | 1 Participants |
| Primary Tumour Location (Number of Participants) Uterine/fallopian tube | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 99 Participants | 94 Participants | 193 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 8 Participants | 12 Participants |
| Sex/Gender, Customized Female | 106 Participants | 105 Participants | 211 Participants |
| Tumour Grade Missing | 0 Participants | 4 Participants | 4 Participants |
| Tumour Grade Mod. Differentiated (G2) | 25 Participants | 29 Participants | 54 Participants |
| Tumour Grade Unassessable (GX) | 14 Participants | 15 Participants | 29 Participants |
| Tumour Grade Unavailable (G3) | 53 Participants | 45 Participants | 98 Participants |
| Tumour Grade Undifferentiated (G4) | 6 Participants | 4 Participants | 10 Participants |
| Tumour Grade Well Differentiated (G1) | 8 Participants | 8 Participants | 16 Participants |
| World Health Organization (WHO) Performance Status 0 | 63 Participants | 60 Participants | 123 Participants |
| World Health Organization (WHO) Performance Status 1 | 42 Participants | 41 Participants | 83 Participants |
| World Health Organization (WHO) Performance Status 2 | 1 Participants | 4 Participants | 5 Participants |
| World Health Organization (WHO) Performance Status 3 | 0 Participants | 0 Participants | 0 Participants |
| World Health Organization (WHO) Performance Status 4 | 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 | 102 / 105 | 104 / 106 |
| serious Total, serious adverse events | 46 / 105 | 26 / 106 |
Outcome results
Primary
Objective Response Rate as Evaluated by Response Evaluation Criteria In Solid Tumors ( RECIST)
Number of responders (complete (CR) or partial (PR) responders). CR = disappearance of all target lesions PR = 30% decrease in the sum of the longest diamete. Analysis was based on August 31, 2009 data cut-off , and was performed with patients who had measurable disease and received AZD0530 175mg or Placebo 175mg.
Time frame: Response is evaluated from randomization to objective disease progression per RECIST criteria or death due to any cause in the absence of progression (conducted when a minimum of 78 progression free survival events had occurred)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD0530 , Paclitaxel , Carboplatin i.v. | Objective Response Rate as Evaluated by Response Evaluation Criteria In Solid Tumors ( RECIST) | 47 Participants |
| Carboplatin ,Paclitaxel | Objective Response Rate as Evaluated by Response Evaluation Criteria In Solid Tumors ( RECIST) | 45 Participants |
Secondary
Overall Survival (Number of Deaths)
Interval between date of randomization and death due to any cause. Analysis was based on January 31, 2010 data cut-off and was performed with patients in ITT analysis set who received AZD0530 175mg or Placebo 175mg. At this time, data were still immature and median overall survival was not reached. Number of deaths is presented instead
Time frame: Date of randomization to death due to any cause
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD0530 , Paclitaxel , Carboplatin i.v. | Overall Survival (Number of Deaths) | 12 Participants |
| Carboplatin ,Paclitaxel | Overall Survival (Number of Deaths) | 14 Participants |
Secondary
Progression-free Survival (PFS) as Evaluated by RECIST
Interval between date of randomization and earliest date of objective disease progression per RECIST criteria or death due to any cause in the absence of progression. Analysis was based on August 31, 2009 data cut-off (78 PFS events analysis) and was performed with patients in ITT analysis set who received AZD0530 175mg or Placebo 175mg.
Time frame: Date of randomization to earliest date of objective disease progression or death due to any cause (conducted when a minimum of 78 progression free survival events had occurred)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD0530 , Paclitaxel , Carboplatin i.v. | Progression-free Survival (PFS) as Evaluated by RECIST | 8.28 Months |
| Carboplatin ,Paclitaxel | Progression-free Survival (PFS) as Evaluated by RECIST | 7.79 Months |