Ovarian Neoplasm
Conditions
Keywords
Advanced ovarian cancer, Poly(ADP ribose) polymerases, KU-0059436, AZD2281, BRCA1 protein, BRCA2 protein
Brief summary
The purpose of the study is to see if the drug KU 0059436 is effective and well tolerated in treating patients with measurable BRCA1- or BRCA2-positive advanced ovarian cancer and for whom no curative therapeutic option exists.
Interventions
Sponsors
KuDOS Pharmaceuticals Limited
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Advanced ovarian cancer with positive BRCA1 or BRCA2 status * Failed at least one prior chemotherapy * In investigators opinion, no curative standard therapy exists * Measurable disease
Exclusion criteria
* Brain metastases * Less than 28 days since last treatment used to treat the disease * Considered a poor medical risk due to a serious uncontrolled disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed Objective Tumour Response (According to Response Evaluation Criteria In Solid Tumors (RECIST) | Baseline, every 8 also at study termination or initiation of confounding anti-cancer therapy. | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease from baseline in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit (CB) | End of study | Clinical Benefit (CB) is defined as the percentage of patients with a RECIST tumour response of confirmed complete response, partial response or stable disease for ≥8 weeks) |
| Duration of Response | End of study | Duration of response to olaparib |
| Best Percentage Change in Tumour Size | End of study | The best % change (reduction) from baseline in tumour size (defined as the sum of the longest diameters as measured among all target lesions). |
| Progression-Free Survival (PFS) | End of study | Progression-Free Survival (PFS) is defined as the time from first dose to the earlier date of radiologic progression (as per RECIST criteria) or death by any cause in the absence of objective progression. |
Countries
Australia, Germany, Spain, Sweden, United States
Participant flow
Recruitment details
The first patient was enrolled on June 11, 2007 and efficacy and safety data were collected up to the data cut-off of March 17, 2009. Patients were enrolled at 12 centres in 5 countries: Australia, Germany, Spain, Sweden and the USA.
Pre-assignment details
Two cohorts of women with Breast Cancer gene 1 (BRCA1)- or BRCA2-associated ovarian cancer who had failed at least one prior chemotherapy in the advanced/metastatic setting, were planned to receive olaparib 100 mg bd (n= up to 24) or 400 mg bd (n= up to 40). Enrolment to 2 cohorts was sequential with the 400 mg bd cohort being recruited first.
Participants by arm
| Arm | Count |
|---|---|
| Olaparib 100 mg bd olaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice daily | 24 |
| Olaparib 400 mg bd olaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily | 33 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Death | 1 | 1 |
| Overall Study | Intercurrent illness | 0 | 1 |
| Overall Study | Lack of Efficacy | 16 | 10 |
| Overall Study | Non-compliance | 0 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
Baseline characteristics
| Characteristic | Olaparib 400 mg bd | Total | Olaparib 100 mg bd |
|---|---|---|---|
| Age, Continuous | 56.8 Years STANDARD_DEVIATION 10.49 | 56 Years STANDARD_DEVIATION 9 | 55.6 Years STANDARD_DEVIATION 8.02 |
| BRCA mutation BRCA1 | 21 Participants | 40 Participants | 19 Participants |
| BRCA mutation BRCA2 | 12 Participants | 17 Participants | 5 Participants |
| Sex: Female, Male Female | 33 Participants | 57 Participants | 24 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 | 10 / 24 | 11 / 33 |
| other Total, other adverse events | 23 / 24 | 33 / 33 |
| serious Total, serious adverse events | 7 / 24 | 12 / 33 |
Outcome results
Primary
Confirmed Objective Tumour Response (According to Response Evaluation Criteria In Solid Tumors (RECIST)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease from baseline in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: Baseline, every 8 also at study termination or initiation of confounding anti-cancer therapy.
Population: PP Analysis Set (includes all enrolled patients who complete the trial schedule and medication regime without any major deviations to the protocol - this is the main analysis population, with ITT used to confirm)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olaparib 100 mg bd | Confirmed Objective Tumour Response (According to Response Evaluation Criteria In Solid Tumors (RECIST) | PP Analysis Set | 3 Participants |
| Olaparib 100 mg bd | Confirmed Objective Tumour Response (According to Response Evaluation Criteria In Solid Tumors (RECIST) | ITT Analysis Set | 3 Participants |
| Olaparib 400 mg bd | Confirmed Objective Tumour Response (According to Response Evaluation Criteria In Solid Tumors (RECIST) | PP Analysis Set | 11 Participants |
| Olaparib 400 mg bd | Confirmed Objective Tumour Response (According to Response Evaluation Criteria In Solid Tumors (RECIST) | ITT Analysis Set | 11 Participants |
Secondary
Best Percentage Change in Tumour Size
The best % change (reduction) from baseline in tumour size (defined as the sum of the longest diameters as measured among all target lesions).
Time frame: End of study
Population: PP Analysis Set (includes all enrolled patients who complete the trial schedule and medication regime without any major deviations to the protocol - this is the main analysis population, with ITT used to confirm
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olaparib 100 mg bd | Best Percentage Change in Tumour Size | -5.1 Percent change |
| Olaparib 400 mg bd | Best Percentage Change in Tumour Size | -25.8 Percent change |
Secondary
Clinical Benefit (CB)
Clinical Benefit (CB) is defined as the percentage of patients with a RECIST tumour response of confirmed complete response, partial response or stable disease for ≥8 weeks)
Time frame: End of study
Population: PP Analysis Set (includes all enrolled patients who complete the trial schedule and medication regime without any major deviations to the protocol - this is the main analysis population, with ITT used to confirm)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olaparib 100 mg bd | Clinical Benefit (CB) | 45.5 Percentage of participants |
| Olaparib 400 mg bd | Clinical Benefit (CB) | 71.0 Percentage of participants |
Secondary
Duration of Response
Duration of response to olaparib
Time frame: End of study
Population: PP Analysis Set (includes all enrolled patients who complete the trial schedule and medication regime without any major deviations to the protocol - this is the main analysis population, with ITT used to confirm
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olaparib 100 mg bd | Duration of Response | 242 Days |
| Olaparib 400 mg bd | Duration of Response | 301 Days |
Secondary
Progression-Free Survival (PFS)
Progression-Free Survival (PFS) is defined as the time from first dose to the earlier date of radiologic progression (as per RECIST criteria) or death by any cause in the absence of objective progression.
Time frame: End of study
Population: PP Analysis Set (includes all enrolled patients who complete the trial schedule and medication regime without any major deviations to the protocol - this is the main analysis population, with ITT used to confirm
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olaparib 100 mg bd | Progression-Free Survival (PFS) | 62.5 Days |
| Olaparib 400 mg bd | Progression-Free Survival (PFS) | 226 Days |