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To Study Clinical Effectiveness and Safety of Olaparib Monotherapy in Metastatic Breast Cancer Patients.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03286842
Recruitment Status : Completed
First Posted : September 19, 2017
Results First Posted : January 17, 2023
Last Update Posted : January 17, 2023
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions HER2-ve Metastatic Breast Cancer
Germline BRCA1/2 Mutations
Somatic BRCA1/2 Mutations
Intervention Drug: Olaparib
Enrollment 256
Recruitment Details Participants were enrolled in this study from 17-January-2018 to 21-March-2019 in 125 sites in 15 countries.
Pre-assignment Details Participants who met the inclusion and none of the exclusion criteria were enrolled to the study. All study assessments were performed as per the schedule of assessment. A total of 256 participants were enrolled in this study but, only 255 started treatment.
Arm/Group Title Olaparib
Hide Arm/Group Description Participants received olaparib 300 mg tablets per dose level orally twice daily continuously given as 2 x 150 mg twice daily.
Period Title: Overall Study
Started 255
Completed 175
Not Completed 80
Reason Not Completed
Patients rolled over to another study             80
Arm/Group Title Olaparib
Hide Arm/Group Description Participants received olaparib 300 mg tablets per dose level orally twice daily continuously given as 2 x 150 mg twice daily.
Overall Number of Baseline Participants 255
Hide Baseline Analysis Population Description
The Full Analysis Set consisted of all participants who received at least one dose of study treatment.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Germline BRCA1/2 mutation (gBRCAm) cohort Number Analyzed 252 participants
46.2  (11.30)
Somatic BRCA1/2 mutation (sBRCAm) cohort Number Analyzed 3 participants
55.3  (13.01)
[1]
Measure Analysis Population Description: The number analyzed in both the rows sums up to the overall number.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
gBRCAm cohort Number Analyzed 252 participants
Female
248
  98.4%
Male
4
   1.6%
sBRCAm cohort Number Analyzed 3 participants
Female
3
 100.0%
Male
0
   0.0%
[1]
Measure Analysis Population Description: The number analyzed in both the rows sums up to the overall number.
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
gBRCAm cohort Number Analyzed 252 participants
Hispanic or Latino
13
   5.2%
Not Hispanic or Latino
189
  75.0%
Unknown or Not Reported
50
  19.8%
sBRCAm cohort Number Analyzed 3 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
1
  33.3%
Unknown or Not Reported
2
  66.7%
[1]
Measure Analysis Population Description: The number analyzed in both the rows sums up to the overall number.
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
gBRCAm cohort Number Analyzed 252 participants
American Indian or Alaska Native
1
   0.4%
Asian
22
   8.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
2
   0.8%
White
177
  70.2%
More than one race
0
   0.0%
Unknown or Not Reported
50
  19.8%
sBRCAm cohort Number Analyzed 3 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
  33.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
0
   0.0%
More than one race
0
   0.0%
Unknown or Not Reported
2
  66.7%
[1]
Measure Analysis Population Description: The number analyzed in both the rows sums up to the overall number.
1.Primary Outcome
Title Progression-free Survival (PFS) in Real-world Setting in Germline BRCA Mutated Participants
Hide Description The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting through assessment of PFS in germline BRCA mutated patients was evaluated. PFS is defined as the time from first dose of olaparib to the date of progression or death from any cause. In this study, disease progression in gBRCAm patients will be based on Investigator assessment, i.e. radiological ( e.g. RECIST) progression, symptomatic progression, or clear progression of non-measurable disease, as long as progression can be documented.
Time Frame At every visit until the earliest of disease progression, death or end of study (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.
Arm/Group Title Olaparib gBRCAm Cohort
Hide Arm/Group Description:
Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.
Overall Number of Participants Analyzed 252
Median (95% Confidence Interval)
Unit of Measure: months
8.18
(6.97 to 9.17)
2.Secondary Outcome
Title Overall Survival (OS) in Germline BRCA Mutated Participants
Hide Description The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of overall survival in germline BRCA mutated participants was determined. OS is defined as the time from first dose of olaparib to the date of death from any cause.
Time Frame At every visit and until death or end of study (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.
Arm/Group Title Olaparib gBRCAm Cohort
Hide Arm/Group Description:
Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.
Overall Number of Participants Analyzed 252
Median (95% Confidence Interval)
Unit of Measure: months
24.94
(21.06 to 28.91)
3.Secondary Outcome
Title Time to First Subsequent Treatment or Death (TFST) in Germline BRCA Mutated Participants
Hide Description The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated participants was determined. TFST is defined as the time from first dose of olaparib to first subsequent treatment commencement or death if this occurs before commencement of first subsequent treatment.
Time Frame At every visit until start of first subsequent anticancer treatment or death or end of study (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.
Arm/Group Title Olaparib gBRCAm Cohort
Hide Arm/Group Description:
Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.
Overall Number of Participants Analyzed 252
Median (95% Confidence Interval)
Unit of Measure: months
9.40
(8.61 to 10.64)
4.Secondary Outcome
Title Time to Second Subsequent Treatment or Death (TSST) in Germline BRCA Mutated Participants
Hide Description The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated participants was determined. TSST is defined as the time from first dose of olaparib to second subsequent treatment commencement or death if this occurs before commencement of second subsequent treatment.
Time Frame At every visit until start of second subsequent anticancer treatment or death or end of study (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.
Arm/Group Title Olaparib gBRCAm Cohort
Hide Arm/Group Description:
Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.
Overall Number of Participants Analyzed 252
Median (95% Confidence Interval)
Unit of Measure: months
14.72
(13.50 to 17.25)
5.Secondary Outcome
Title Time to Study Treatment Discontinuation or Death (TDT) in Germline BRCA Mutated Participants
Hide Description The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated patients was determined. TDT is defined as the time from first dose of olaparib to study treatment discontinuation or death if this occurs before discontinuation of study treatment.
Time Frame At every visit and until discontinuation of study treatment or death or end of study (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.
Arm/Group Title Olaparib gBRCAm Cohort
Hide Arm/Group Description:
Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.
Overall Number of Participants Analyzed 252
Median (95% Confidence Interval)
Unit of Measure: months
7.98
(6.90 to 8.54)
6.Secondary Outcome
Title Time to Second Progression or Death (PFS2) in Germline BRCA Mutated Participants
Hide Description The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated participants was determined. PFS2 is defined as the time from first dose of olaparib to the earliest progression event subsequent to that used for the primary variable PFS or death from any cause. Patients alive and for whom a second disease progression has not been observed will be censored at the last time known to be alive and without a second disease progression. In this study, disease progression in gBRCAm patients will be based on Investigator assessment, i.e. radiological ( e.g. RECIST) progression, symptomatic progression, or clear progression of non-measurable disease, as long as progression can be documented
Time Frame At every visit until second progression or death or end of study (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.
Arm/Group Title Olaparib gBRCAm Cohort
Hide Arm/Group Description:
Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.
Overall Number of Participants Analyzed 252
Median (95% Confidence Interval)
Unit of Measure: months
14.49
(13.17 to 17.05)
7.Secondary Outcome
Title Clinical Response Rate (CRR) in Germline BRCA Mutated Participants
Hide Description The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of clinical response rate and duration of clinical response in germline BRCA mutated participants was determined. CRR is defined as the percentage of patients assessed by the Investigator as responding. Response in gBRCAm patients were based on the Investigator's assessment. Data obtained up until progression, or last evaluable assessment in the absence of progression, will be included in the assessment of CRR. However, any responses, which occurred after a further anticancer therapy was received, will not be included in the numerator for the CRR calculation.
Time Frame At every visit until disease progression or death or end of study (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set consisted of all participants who received at least one dose of study treatment.
Arm/Group Title Olaparib gBRCAm Cohort
Hide Arm/Group Description:
Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.
Overall Number of Participants Analyzed 252
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
49.6
(43.3 to 55.9)
8.Secondary Outcome
Title Duration of Clinical Response (DoCR) in Germline BRCA Mutated Participants
Hide Description The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of clinical response rate and duration of clinical response in germline BRCA mutated participants was determined. DoCR is defined as the time from the date the Investigator first assessed the patient as responding to the date the Investigator assessed the patient as progressing or the date of death from any cause. The end of response should coincide with the date of progression or death used for the PFS endpoint. The time of the initial response will be defined as the latest of the dates contributing towards the first visit response. If a patient does not progress following a response, they will be censored at the PFS censoring date.
Time Frame At every visit until disease progression or death or end of study (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set consisted of all participants who received at least one dose of study treatment.
Arm/Group Title Olaparib gBRCAm Cohort
Hide Arm/Group Description:
Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.
Overall Number of Participants Analyzed 252
Median (Inter-Quartile Range)
Unit of Measure: Months
8.0
(4.2 to 18.6)
9.Secondary Outcome
Title Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description The safety and tolerability of olaparib treatment in HER2-ve metastatic breast cancer patients in a real-word setting was evaluated.
Time Frame From Screening (Day -28 to Day -1) until post DCO [up to 3 years]
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.
Arm/Group Title Olaparib gBRCAm Cohort Olaparib sBRCAm Cohort
Hide Arm/Group Description:
Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.
Participants received olaparib 300 mg tablets per dose level orally twice daily continuously given as 2 x 150 mg twice daily.
Overall Number of Participants Analyzed 252 3
Measure Type: Count of Participants
Unit of Measure: Participants
Any AE
243
  96.4%
3
 100.0%
Any AE casually related to study treatment
214
  84.9%
3
 100.0%
Any AE of CTCAE grade 3 or higher
69
  27.4%
2
  66.7%
Any AE of CTCAE grade 3 or higher, causally related to study treatment
44
  17.5%
1
  33.3%
Any AE with outcome = death
0
   0.0%
0
   0.0%
Any AE with outcome = death, causally related to study treatment
0
   0.0%
0
   0.0%
Any SAE (including events with outcome = death)
32
  12.7%
1
  33.3%
Any SAE (including events with outcome = death), causally related to study treatment
10
   4.0%
0
   0.0%
Any AE leading to discontinuation of study treatment
16
   6.3%
0
   0.0%
Any AE leading to discontinuation of study treatment, causally related to study treatment
11
   4.4%
0
   0.0%
Time Frame From Screening (Day -28 to -1) until post DCO [up to 3 years].
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Olaparib gBRCAm Cohort Olaparib sBRCAm Cohort
Hide Arm/Group Description Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily. Participants received olaparib 300 mg tablets per dose level orally twice daily continuously given as 2 x 150 mg twice daily.
All-Cause Mortality
Olaparib gBRCAm Cohort Olaparib sBRCAm Cohort
Affected / at Risk (%) Affected / at Risk (%)
Total   140/252 (55.56%)      2/3 (66.67%)    
Hide Serious Adverse Events
Olaparib gBRCAm Cohort Olaparib sBRCAm Cohort
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   32/252 (12.70%)      1/3 (33.33%)    
Blood and lymphatic system disorders     
Anaemia * 1  7/252 (2.78%)  10 0/3 (0.00%)  0
Febrile neutropenia * 1  2/252 (0.79%)  2 0/3 (0.00%)  0
Pancytopenia * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Cardiac disorders     
Pericardial effusion * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Gastrointestinal disorders     
Ileus paralytic * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Nausea * 1  1/252 (0.40%)  2 0/3 (0.00%)  0
Pancreatitis acute * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Vomiting * 1  2/252 (0.79%)  3 0/3 (0.00%)  0
General disorders     
Asthenia * 1  2/252 (0.79%)  2 0/3 (0.00%)  0
Non-cardiac chest pain * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Pyrexia * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Infections and infestations     
Abscess * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
COVID-19 * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
COVID-19 pneumonia * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Cellulitis * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Chest wall abscess * 1  1/252 (0.40%)  4 0/3 (0.00%)  0
Device related infection * 1  1/252 (0.40%)  2 0/3 (0.00%)  0
H1N1 influenza * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Influenza * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Skin infection * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Urinary tract infection * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Urosepsis * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Viral infection * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Pneumonia * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Injury, poisoning and procedural complications     
Head injury * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Radiation necrosis * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Spinal compression fracture * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Spinal fracture * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Investigations     
General physical condition abnormal * 1  0/252 (0.00%)  0 1/3 (33.33%)  1
Metabolism and nutrition disorders     
Hyperglycaemia * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Bone pain * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Muscle spasms * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Bladder cancer stage 0, with cancer in situ * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Myelodysplastic syndrome * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Pancreatic carcinoma * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Nervous system disorders     
Epilepsy * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Psychiatric disorders     
Anxiety * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Psychiatric decompensation * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Lung disorder * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Pleural effusion * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Pleurisy * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
Pulmonary embolism * 1  1/252 (0.40%)  1 0/3 (0.00%)  0
1
Term from vocabulary, MedDRA v24.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Olaparib gBRCAm Cohort Olaparib sBRCAm Cohort
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   243/252 (96.43%)      3/3 (100.00%)    
Blood and lymphatic system disorders     
Anaemia * 1  98/252 (38.89%)  168 1/3 (33.33%)  1
Leukopenia * 1  22/252 (8.73%)  37 0/3 (0.00%)  0
Neutropenia * 1  41/252 (16.27%)  71 1/3 (33.33%)  6
Gastrointestinal disorders     
Abdominal pain * 1  21/252 (8.33%)  25 1/3 (33.33%)  1
Abdominal pain upper * 1  19/252 (7.54%)  31 0/3 (0.00%)  0
Constipation * 1  30/252 (11.90%)  37 3/3 (100.00%)  3
Diarrhoea * 1  53/252 (21.03%)  72 2/3 (66.67%)  4
Dyspepsia * 1  25/252 (9.92%)  30 0/3 (0.00%)  0
Nausea * 1  140/252 (55.56%)  236 2/3 (66.67%)  2
Vomiting * 1  67/252 (26.59%)  111 0/3 (0.00%)  0
General disorders     
Asthenia * 1  70/252 (27.78%)  94 2/3 (66.67%)  3
Fatigue * 1  59/252 (23.41%)  84 0/3 (0.00%)  0
Pyrexia * 1  31/252 (12.30%)  43 1/3 (33.33%)  1
Infections and infestations     
Nasopharyngitis * 1  14/252 (5.56%)  17 0/3 (0.00%)  0
Upper respiratory tract infection * 1  13/252 (5.16%)  14 0/3 (0.00%)  0
Urinary tract infection * 1  16/252 (6.35%)  22 0/3 (0.00%)  0
Investigations     
Neutrophil count decreased * 1  14/252 (5.56%)  18 0/3 (0.00%)  0
Metabolism and nutrition disorders     
Decreased appetite * 1  31/252 (12.30%)  36 0/3 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  39/252 (15.48%)  55 1/3 (33.33%)  1
Back pain * 1  28/252 (11.11%)  32 1/3 (33.33%)  1
Myalgia * 1  17/252 (6.75%)  17 2/3 (66.67%)  2
Pain in extremity * 1  21/252 (8.33%)  24 0/3 (0.00%)  0
Nervous system disorders     
Dizziness * 1  23/252 (9.13%)  28 0/3 (0.00%)  0
Dysgeusia * 1  16/252 (6.35%)  18 0/3 (0.00%)  0
Headache * 1  47/252 (18.65%)  103 2/3 (66.67%)  2
Psychiatric disorders     
Insomnia * 1  15/252 (5.95%)  15 0/3 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Cough * 1  35/252 (13.89%)  40 1/3 (33.33%)  1
Dyspnoea * 1  21/252 (8.33%)  24 0/3 (0.00%)  0
1
Term from vocabulary, MedDRA v24.0
*
Indicates events were collected by non-systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
This document contains trade secrets and confidential commercial information, disclosure of which is prohibited without providing advance notice to AstraZeneca and opportunity to object.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Clinical Lead
Organization: AstraZeneca Clinical Study Information Center
Phone: 1-877-240-9479
EMail: information.center@astrazeneca.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03286842    
Other Study ID Numbers: D0816C00018
First Submitted: August 17, 2017
First Posted: September 19, 2017
Results First Submitted: October 7, 2022
Results First Posted: January 17, 2023
Last Update Posted: January 17, 2023