Advanced Tumours, Breast, Ovarian, Pancreatic, Prostate
Conditions
Keywords
olaparib, PARP inhibitors, genetic BRCA1 mutation, BRCA2 mutation, solid tumour refractory
Brief summary
To assess the efficacy of oral olaparib in patients with advanced cancer who have a confirmed genetic BRCA1 and/or BRCA2 mutation, by assessment of tumour response
Interventions
DRUGolaparib
Tablets Oral BID
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed documented deleterious or suspected deleterious BRCA mutation. (The presence of a loss-of-function germline mutation in the BRCA1 and/or BRCA2 gene must be confirmed prior to consent according to local practice). * Confirmed malignant solid tumours for which no standard treatment exists * At least one lesion (measurable and/or non measurable) at baseline that can be accurately assessed by CT/MRI and is suitable for repeated assessment at follow up visits
Exclusion criteria
* Any previous treatment with a PARP inhibitor, including olaparib * Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication * Patients receiving any systematic chemotherapy, radiotherapy (except for palliative reasons) within 2 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumour Response Rate | Tumour assessments carried out at baseline ie 28 days before first study drug dose and then every 8 weeks up to 6 months after starting study treatment, then every 12 weeks until objective disease progression, assessed maximum up to 29 months | Tumour response rate is the proportion of patients who experienced complete or partial response at least once during the assessment period, according to the definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Tumour assessments are carried out at baseline ie 28 days before first study drug dose and then every 8 weeks up to 6 months after starting study treatment, then every 12 weeks until objective disease progression, assessed maximum up to 29 months | Progression free survival is defined as the duration from first dose till objective progression or death. In absence of progression or death, the time is calculated from first dose till last evaluable scanning visit. |
| Overall Survival | Survival follow-up from first dose till death of the patient or till end of study in absence of death, assessed maximum up to 29 months | Overall survival is defined as the duration from first dose till death. In absence of death, the time is calculated from first dose till the date subject last known to be alive. |
| Objective Response Rate | Tumour assessments carried out at baseline ie 28 days before first study drug dose and then every 8 weeks up to 6 months after starting study treatment, then every 12 weeks until objective disease progression, assessed maximum up to 29 months | Objective response rate is the proportion of patients with at least one measurable lesion at baseline, who experienced complete or partial response at least once during the assessment period, according to the definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1). |
| Duration of Response | From onset of first occurrence of complete or partial response till documented progression or death by any cause in the absence of progression, assessed maximum up to 29 months | Duration of response is calculated from the date of first documented response (complete or partial) until date of documented progression (as defined by RECIST 1.1) or death (by any cause) in the absence of disease progression. |
| Disease Control Rate at Week 16 | Tumour assessments carried out at baseline ie 28 days before first study drug dose and then at week 8 and week 16 | Disease control rate is the proportion of patients with best response of complete or partial response or stable disease according to definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) till week 16. |
| Overall Survival Rate at 12 Months | Survival follow-up from first dose till death of the patient or till end of study in absence of death, assessed maximum up to 29 months | Overall survival rate at 12 months is defined as the proportion of patients who are alive 12 months after date of first dose |
Countries
Australia, Germany, Israel, Spain, Sweden, United States
Participant flow
Recruitment details
This study was conducted at 13 sites across Israel, Germany, Spain, Australia, USA, Sweden. Enrolment started in Feb 2010 and was completed in Jul 2012. In total, 298 patients had received treatment (olaparib).
Pre-assignment details
Patients \>17 years age with histologically and/or cytologically confirmed malignant solid tumours, refractory to standard therapy for which no suitable effective/curative therapy. Patients with confirmed deleterious or suspected deleterious BRCA mutation, Eastern Co-operative Oncology Group performance status ≤2 and life expectancy of ≥12 weeks. In total, 298 patients had received treatment.
Participants by arm
| Arm | Count |
|---|---|
| Breast Cancer Patients with primary cancer site = breast. Receiving olaparib 400mg BID | 62 |
| Ovarian Cancer Patients with primary cancer site = ovary. Receiving olaparib 400mg BID | 193 |
| Pancreatic Cancer Patients with primary cancer site = pancreas. Receiving olaparib 400mg BID | 23 |
| Prostate Cancer Patients with primary cancer site = prostate. Receiving olaparib 400mg BID | 8 |
| Other Cancers Patients with other primary cancers. Receiving olaparib 400mg BID | 12 |
| Total | 298 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Death | 41 | 103 | 18 | 5 | 8 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Patients reached data cut-off | 12 | 53 | 2 | 2 | 3 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 11 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Breast Cancer | Ovarian Cancer | Pancreatic Cancer | Prostate Cancer | Other Cancers | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 47.6 years STANDARD_DEVIATION 9.69 | 57.2 years STANDARD_DEVIATION 9.28 | 57.1 years STANDARD_DEVIATION 7.99 | 66.6 years STANDARD_DEVIATION 9.86 | 54.9 years STANDARD_DEVIATION 12.38 | 55.3 years STANDARD_DEVIATION 10.3 |
| Age, Customized >=50 to <65 years | 28 Participants | 117 Participants | 14 Participants | 3 Participants | 5 Participants | 167 Participants |
| Age, Customized < 50 years | 33 Participants | 40 Participants | 6 Participants | 0 Participants | 4 Participants | 83 Participants |
| Age, Customized >= 65 years | 1 Participants | 36 Participants | 3 Participants | 5 Participants | 3 Participants | 48 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 8 Participants | 1 Participants | 0 Participants | 1 Participants | 11 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 60 Participants | 183 Participants | 21 Participants | 8 Participants | 11 Participants | 283 Participants |
| Sex: Female, Male Female | 61 Participants | 193 Participants | 10 Participants | 0 Participants | 8 Participants | 272 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 13 Participants | 8 Participants | 4 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 290 / 298 |
| serious Total, serious adverse events | 90 / 298 |
Outcome results
Primary
Tumour Response Rate
Tumour response rate is the proportion of patients who experienced complete or partial response at least once during the assessment period, according to the definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1).
Time frame: Tumour assessments carried out at baseline ie 28 days before first study drug dose and then every 8 weeks up to 6 months after starting study treatment, then every 12 weeks until objective disease progression, assessed maximum up to 29 months
Population: Full analysis set - all treated patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Breast Cancer | Tumour Response Rate | 12.9 Percentage of participants |
| Ovarian Cancer | Tumour Response Rate | 31.1 Percentage of participants |
| Pancreatic Cancer | Tumour Response Rate | 21.7 Percentage of participants |
| Prostate Cancer | Tumour Response Rate | 50 Percentage of participants |
| Other Cancers | Tumour Response Rate | 8.3 Percentage of participants |
| All Patients | Tumour Response Rate | 26.2 Percentage of participants |
Secondary
Disease Control Rate at Week 16
Disease control rate is the proportion of patients with best response of complete or partial response or stable disease according to definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) till week 16.
Time frame: Tumour assessments carried out at baseline ie 28 days before first study drug dose and then at week 8 and week 16
Population: Full analysis set - all treated patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Breast Cancer | Disease Control Rate at Week 16 | 37.1 Percentage of participants |
| Ovarian Cancer | Disease Control Rate at Week 16 | 58 Percentage of participants |
| Pancreatic Cancer | Disease Control Rate at Week 16 | 47.8 Percentage of participants |
| Prostate Cancer | Disease Control Rate at Week 16 | 62.5 Percentage of participants |
| Other Cancers | Disease Control Rate at Week 16 | 33.3 Percentage of participants |
| All Patients | Disease Control Rate at Week 16 | 52 Percentage of participants |
Secondary
Duration of Response
Duration of response is calculated from the date of first documented response (complete or partial) until date of documented progression (as defined by RECIST 1.1) or death (by any cause) in the absence of disease progression.
Time frame: From onset of first occurrence of complete or partial response till documented progression or death by any cause in the absence of progression, assessed maximum up to 29 months
Population: Full analysis set - all treated patients who had at least one complete or partial response during the assessment period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Breast Cancer | Duration of Response | 204 days |
| Ovarian Cancer | Duration of Response | 225 days |
| Pancreatic Cancer | Duration of Response | 134 days |
| Prostate Cancer | Duration of Response | 326.5 days |
| Other Cancers | Duration of Response | 165 days |
| All Patients | Duration of Response | 208 days |
Secondary
Objective Response Rate
Objective response rate is the proportion of patients with at least one measurable lesion at baseline, who experienced complete or partial response at least once during the assessment period, according to the definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1).
Time frame: Tumour assessments carried out at baseline ie 28 days before first study drug dose and then every 8 weeks up to 6 months after starting study treatment, then every 12 weeks until objective disease progression, assessed maximum up to 29 months
Population: Measurable disease analysis set - all treated patients having at least one measurable lesion at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Breast Cancer | Objective Response Rate | 13.8 Percentage of participants |
| Ovarian Cancer | Objective Response Rate | 35.9 Percentage of participants |
| Pancreatic Cancer | Objective Response Rate | 21.7 Percentage of participants |
| Prostate Cancer | Objective Response Rate | 57.1 Percentage of participants |
| Other Cancers | Objective Response Rate | 9.1 Percentage of participants |
| All Patients | Objective Response Rate | 29.3 Percentage of participants |
Secondary
Overall Survival
Overall survival is defined as the duration from first dose till death. In absence of death, the time is calculated from first dose till the date subject last known to be alive.
Time frame: Survival follow-up from first dose till death of the patient or till end of study in absence of death, assessed maximum up to 29 months
Population: Full analysis set - all treated patients. The Other cancer group was not analysed in accordance with the protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Breast Cancer | Overall Survival | 11.01 months |
| Ovarian Cancer | Overall Survival | 16.62 months |
| Pancreatic Cancer | Overall Survival | 9.81 months |
| Prostate Cancer | Overall Survival | 18.38 months |
Secondary
Overall Survival Rate at 12 Months
Overall survival rate at 12 months is defined as the proportion of patients who are alive 12 months after date of first dose
Time frame: Survival follow-up from first dose till death of the patient or till end of study in absence of death, assessed maximum up to 29 months
Population: Full analysis set - all treated patients. The Other cancer group was not analysed in accordance with the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Breast Cancer | Overall Survival Rate at 12 Months | 44.7 Percentage of participants |
| Ovarian Cancer | Overall Survival Rate at 12 Months | 64.4 Percentage of participants |
| Pancreatic Cancer | Overall Survival Rate at 12 Months | 40.9 Percentage of participants |
| Prostate Cancer | Overall Survival Rate at 12 Months | 50 Percentage of participants |
Secondary
Progression Free Survival
Progression free survival is defined as the duration from first dose till objective progression or death. In absence of progression or death, the time is calculated from first dose till last evaluable scanning visit.
Time frame: Tumour assessments are carried out at baseline ie 28 days before first study drug dose and then every 8 weeks up to 6 months after starting study treatment, then every 12 weeks until objective disease progression, assessed maximum up to 29 months
Population: Full analysis set - all treated patients. The Other cancer group was not analysed in accordance with the protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Breast Cancer | Progression Free Survival | 3.68 months |
| Ovarian Cancer | Progression Free Survival | 7.03 months |
| Pancreatic Cancer | Progression Free Survival | 4.55 months |
| Prostate Cancer | Progression Free Survival | 7.15 months |