A Phase 2 interventional study of Olaparib in Breast Neoplasms, sponsored by AstraZeneca. Completed at 17 sites in 8 countries. Open to female participants aged 18 Years to 130 Years. Per ClinicalTrials.gov, last updated 2024-01-19.
Sponsored by AstraZeneca · Phase 2, Interventional, and Treatment
The purpose of the study is to see if the drug KU-0059436 (olaparib) is effective and well tolerated in treating participants with measurable breast cancer gene (BRCA)1- or BRCA2-positive advanced breast cancer and for whom no curative therapeutic option exists.
This is a Phase II, open-label, non-comparative, international, multicenter study to assess the efficacy and safety of olaparib when given orally twice daily (bd) in participants with advanced BRCA1- or BRCA2- associated breast cancer. Two sequential participant cohorts will receive continuous oral olaparib in 28-day cycles. The first cohort will receive 400 mg bd and the second cohort will receive 100 mg bd.
12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.
This study's enrollment of 54 is below the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.
Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Participants will receive two 50 mg capsules in the morning and two 50 mg capsules in the evening in 28-days cycle until confirmed disease progression, continuous treatment interruption, unacceptable toxicity or any other discontinuation criterion is met.
Drug: Olaparib
Participants will receive eight 50 mg capsules in the morning and eight 50 mg capsules in the evening in 28-days cycle until confirmed disease progression, continuous treatment interruption, unacceptable toxicity or any other discontinuation criterion is met.
Drug: Olaparib
Participants will receive capsules of olaparib orally as stated in arm description.
Also known as: AZD2281, KU-0059436
Confirmed Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
The ORR is the percentage of participants whose best tumor response is either complete response (CR) or partial response (PR), according to the RECIST v1.0 criteria. The CR is defined as disappearance of all target lesions (TLs). The PR is defined as at least a 30% decrease in the sum of longest diameters (LD) taking as reference the baseline sum of LD. Percentage of participants with ORR is reported.
Time frame: Baseline (Days -28 to 0), Day 1 of Cycle 3, thereafter every alternate cycles until study termination or withdrawal (approximately up to 2 years)
Duration of Response (DoR) to Olaparib
Duration of response is defined as the date of progression per RECIST criteria - the date when CR or PR \[whichever is earliest\] is confirmed + 1. The CR is defined as disappearance of all TLs. The PR is defined as at least a 30% decrease in the sum of LD taking as reference the baseline sum of LD. Duration of response was analyzed for those participants who had OR.
Time frame: Baseline (Days -28 to 0), Day 1 of Cycle 3, thereafter every alternate cycles until study termination or withdrawal (approximately up to 2 years)
Clinical Benefit Rate (CBR)
The CBR is defined as the percentage of participants with a RECIST tumor response of confirmed CR, PR or stable disease (SD) for ≥ 8 weeks +/- 1 week visit window. The CR is defined as disappearance of all TLs. The PR is defined as at least a 30% decrease in the sum of LD taking as reference the baseline sum of LD. Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum of LD since the treatment started.
Time frame: From Day 1 of Cycle 3 through study withdrawal (approximately up to 2 years)
Best Percentage Change in Tumor Size
The tumor size is defined as the sum of the longest diameters as measured among all target lesions. At each assessment, the percentage change in tumor size is defined as 100 × 1 - (sum of all target lesion diameters at visit/sum of all target lesion diameters at baseline).
Time frame: Baseline (Days -28 to 0) through study withdrawal (approximately up to 2 years)
Progression-free Survival (PFS)
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. Those participants who were withdrawn from the study without disease progression were regarded as censored at their last evaluable RECIST assessment. Where participants had not progressed at the termination of the study, they were also regarded as censored at their last evaluable RECIST assessment. PFS was analyzed using Kaplan-Meier estimate.
Time frame: Baseline (Days -28 to 0), Day 1 of Cycle 3, thereafter every alternate cycles until study termination or withdrawal (approximately up to 2 years)
Number of Participants With Improvement in Eastern Co-operative Oncology Group (ECOG) Performance Status Total Score From Baseline
ECOG performance status is used by researchers to assess how a participant's disease is progressing. The scores are: 0=Fully Active, able to carry out work without restrictions; 1=Restricted activity and able to carry out light work or sedentary nature; 2=capable of self-care but unable to carry out work activities; 3=Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=Completely Disabled, and totally confined to bed or chair; 5=Dead. Change in ECOG performance status was defined as improved (less than the baseline value), no change (same as at baseline), worsened (greater than the baseline value) or missing (score is missing or was not recorded at baseline). If no measurement was recorded at Cycle 1 Day 1, the change was calculated in relation to the last recorded ECOG value prior to Day 1.
Time frame: Screening (Days -7 to 0), Day 1 Cycle 7 (ie, after completing 6 cycles of treatment) and study withdrawal (approximately up to 2 years).
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Time frame: Day 1 through Day 480 (maximum observed duration)
Number of Participants With Clinically Significant Changes in Vital Signs From Baseline
Number of participants with clinically significant changes in vital signs are reported. Vital sign parameters included body temperature, blood pressure, and pulse rate.
Time frame: Day 1 through Day 480 (maximum observed duration)
Number of Participants With at Least 2-Grade Change From Baseline to Worst Toxicity Grade in Clinical Laboratory Parameters
Number of participants with at least 2-grade change from baseline to worst toxicity grade in clinical laboratory parameters are reported. Laboratory parameters included hematology, clinical chemistry, and urinalysis.
Time frame: Day 1 through Day 480 (maximum observed duration)
The study was conducted at 13 centers in 5 countries (Australia, Germany, Sweden, UK and the USA).
| Milestone | Olaparib 100 mg | Olaparib 400 mg |
|---|---|---|
| Started | 27 | 27 |
| Completed | 13 | 18 |
| Not completed | 14 | 9 |
| Withdrew: Withdrawal by subject | 1 | 0 |
| Withdrew: Disease progression | 11 | 8 |
| Withdrew: Death | 2 | 1 |
The ORR is the percentage of participants whose best tumor response is either complete response (CR) or partial response (PR), according to the RECIST v1.0 criteria. The CR is defined as disappearance of all target lesions (TLs). The PR is defined as at least a 30% decrease in the sum of longest diameters (LD) taking as reference the baseline sum of LD. Percentage of participants with ORR is reported.
| Percentage of participants | Olaparib 100 mg | Olaparib 400 mg |
|---|---|---|
| Confirmed Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | 25.0 | 42.3 |
Duration of response is defined as the date of progression per RECIST criteria - the date when CR or PR \[whichever is earliest\] is confirmed + 1. The CR is defined as disappearance of all TLs. The PR is defined as at least a 30% decrease in the sum of LD taking as reference the baseline sum of LD. Duration of response was analyzed for those participants who had OR.
| Days | Olaparib 100 mg | Olaparib 400 mg |
|---|---|---|
| Duration of Response (DoR) to Olaparib | 140.5 ± 55 | 144.0 ± 92 |
The CBR is defined as the percentage of participants with a RECIST tumor response of confirmed CR, PR or stable disease (SD) for ≥ 8 weeks +/- 1 week visit window. The CR is defined as disappearance of all TLs. The PR is defined as at least a 30% decrease in the sum of LD taking as reference the baseline sum of LD. Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum of LD since the treatment started.
| Percentage of Participants | Olaparib 100 mg | Olaparib 400 mg |
|---|---|---|
| Clinical Benefit Rate (CBR) | 70.8 ± 50.8 | 84.6 ± 66.5 |
The tumor size is defined as the sum of the longest diameters as measured among all target lesions. At each assessment, the percentage change in tumor size is defined as 100 × 1 - (sum of all target lesion diameters at visit/sum of all target lesion diameters at baseline).
| Best percentage change in tumor size | Olaparib 100 mg | Olaparib 400 mg |
|---|---|---|
| Best Percentage Change in Tumor Size | -10.14 (-68.9 to 286.7) | -29.43 (-100.0 to 26.7) |
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. Those participants who were withdrawn from the study without disease progression were regarded as censored at their last evaluable RECIST assessment. Where participants had not progressed at the termination of the study, they were also regarded as censored at their last evaluable RECIST assessment. PFS was analyzed using Kaplan-Meier estimate.
| Days | Olaparib 100 mg | Olaparib 400 mg |
|---|---|---|
| Progression-free Survival (PFS) | 122 (67 to 167) | 193.5 (140 to 226) |
ECOG performance status is used by researchers to assess how a participant's disease is progressing. The scores are: 0=Fully Active, able to carry out work without restrictions; 1=Restricted activity and able to carry out light work or sedentary nature; 2=capable of self-care but unable to carry out work activities; 3=Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=Completely Disabled, and totally confined to bed or chair; 5=Dead. Change in ECOG performance status was defined as improved (less than the baseline value), no change (same as at baseline), worsened (greater than the baseline value) or missing (score is missing or was not recorded at baseline). If no measurement was recorded at Cycle 1 Day 1, the change was calculated in relation to the last recorded ECOG value prior to Day 1.
| Participants | Olaparib 100 mg | Olaparib 400 mg |
|---|---|---|
| Cycle 7 Day 1 | 1 | 6 |
| Withdrawal visit | 0 | 2 |
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
| Participants | Olaparib 100 mg | Olaparib 400 mg |
|---|---|---|
| Any TEAE | 27 | 27 |
| Any TESAE | 5 | 9 |
Number of participants with clinically significant changes in vital signs are reported. Vital sign parameters included body temperature, blood pressure, and pulse rate.
| Participants | Olaparib 100 mg | Olaparib 400 mg |
|---|---|---|
| Tachycardia | 1 | 0 |
| Supraventricular arrhythmia | 1 | 0 |
Number of participants with at least 2-grade change from baseline to worst toxicity grade in clinical laboratory parameters are reported. Laboratory parameters included hematology, clinical chemistry, and urinalysis.
| Participants | Olaparib 100 mg | Olaparib 400 mg |
|---|---|---|
| Hemoglobin | 2 | 3 |
| White blood cells | 5 | 11 |
| Absolute neutrophil count | 3 | 6 |
| Lymphocytes | 3 | 2 |
| Platelets | 0 | 2 |
| Activated partial thromboplastin time | 1 | 2 |
| Alanine aminotransferase | 2 | 3 |
| Aspartate aminotransferase | 3 | 1 |
| Alkaline phosphatase | 1 | 0 |
| Gamma glutamyl transferase | 4 | 2 |
| Albumin | 1 | 0 |
| Total bilirubin | 0 | 4 |
| Sodium (decrease) | 1 | 0 |
| Potassium (increase) | 0 | 1 |
| Creatinine | 0 | 2 |
| Glucose (increase) | 2 | 2 |
| Glucose (decrease) | 3 | 3 |
| Calcium (decrease) | 3 | 3 |
| Amylase | 1 | 0 |
| Lipase | 2 | 0 |
Collected over Day 1 to 480 (maximum observed duration). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Olaparib 100 mg | 3/27 (11.1%) | 5/27 (18.5%) | 27/27 (100%) |
| Olaparib 400 mg | 6/27 (22.2%) | 9/27 (33.3%) | 26/27 (96.3%) |
| Event | Olaparib 100 mg | Olaparib 400 mg |
|---|---|---|
| NauseaGastrointestinal disorders | 0/27 | 3/27 |
| VomitingGastrointestinal disorders | 0/27 | 2/27 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 2/27 | 0/27 |
| AnaemiaBlood and lymphatic system disorders | 1/27 | 1/27 |
| Angina pectorisCardiac disorders | 0/27 | 1/27 |
| Allergic transfusion reactionInjury, poisoning and procedural complications | 0/27 | 1/27 |
| Haemoglobin decreasedInvestigations | 0/27 | 1/27 |
| Musculoskeletal chest painMusculoskeletal and connective tissue disorders | 1/27 | 0/27 |
| Cerebral haemorrhageNervous system disorders | 1/27 | 0/27 |
| ConvulsionNervous system disorders | 1/27 | 0/27 |
| Event | Olaparib 100 mg | Olaparib 400 mg |
|---|---|---|
| FatigueGeneral disorders | 17/27 | 19/27 |
| NauseaGastrointestinal disorders | 15/27 | 14/27 |
| VomitingGastrointestinal disorders | 6/27 | 10/27 |
| HeadacheNervous system disorders | 6/27 | 10/27 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 9/27 | 1/27 |
| ConstipationGastrointestinal disorders | 8/27 | 6/27 |
| DiarrhoeaGastrointestinal disorders | 4/27 | 8/27 |
| CoughRespiratory, thoracic and mediastinal disorders | 8/27 | 4/27 |
| Pain in extremityMusculoskeletal and connective tissue disorders | 7/27 | 2/27 |
| InsomniaPsychiatric disorders | 7/27 | 2/27 |
The full analysis set comprised of all enrolled participants with positive BRCA status, who took at least one dose of investigational medicinal product irrespective of whether they completed the trial schedule and IMP regime or not.
| Age, Continuous(Years) | Olaparib 100 mg | Olaparib 400 mg | Total |
|---|---|---|---|
| Mean | 44.7 ± 11.99 | 44.7 ± 9.55 | 44.7 ± 10.74 |
| Sex: Female, Male(Participants) | Olaparib 100 mg | Olaparib 400 mg | Total |
|---|---|---|---|
| Female | 27 | 27 | 54 |
| Male | 0 | 0 | 0 |
| Ethnicity (NIH/OMB)(Participants) | Olaparib 100 mg | Olaparib 400 mg | Total |
|---|---|---|---|
| Hispanic or Latino | 2 | 2 | 4 |
| Not Hispanic or Latino | 4 | 6 | 10 |
| Unknown or Not Reported | 21 | 19 | 40 |
| Race (NIH/OMB)(Participants) | Olaparib 100 mg | Olaparib 400 mg | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 1 | 1 | 2 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 1 | 0 | 1 |
| White | 25 | 26 | 51 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
Plan to share: Yes — Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Supporting information: Study protocol, Sap
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