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Study to Compare the Efficacy and Safety of Olaparib When Given in Combination With Carboplatin and Paclitaxel, Compared With Carboplatin and Paclitaxel in Patients With Advanced Ovarian Cancer

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: NCT01081951
Recruitment Status : Active, not recruiting
First Posted : March 5, 2010
Results First Posted : December 10, 2012
Last Update Posted : September 14, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Ovarian Cancer
Interventions Drug: olaparib
Drug: paclitaxel
Drug: carboplatin
Drug: Drug: carboplatin
Enrollment 162
Recruitment Details The first patient was enrolled on 12-Feb-2010. The last patient was enrolled on 15-Jul-2010. Patients were enrolled at 43 sites in 12 countries: Australia, Belgium, Canada, Czech Republic, Germany, Italy, Japan, the Netherlands, Panama, Spain, the UK and the USA. 173 patients were screened and 162 patients were enrolled to receive treatment.
Pre-assignment Details Patient randomisation was stratified(using an interactive voice response [IVR]system) based on:1) number of prior platinum-containing treatment lines received(1or>1) and 2)time to disease progression following completion of the previous platinum-containing therapy(>6to<=12 months or>12 months).Six patients in the C6/P arm did not receive treatment.
Arm/Group Title Olaparib/Carboplatin AUC4/Paclitaxel Carboplatin AUC6/Paclitaxel
Hide Arm/Group Description

Olaparib orally (po) (200mg bd Days 1-10 of a 21-day cycle) in combination with paclitaxel intravenous (iv) (175 mg/m2 Day 1 of a 21-day cycle) and carboplatin iv (AUC4 Day 1 of a 21-day cycle) for at least 4 cycles.

Followed by olaparib monotherapy maintenance (400mg bd continuous dosing)

Paclitaxel iv (175mg/m2 Day 1 of a 21-day cycle) and carboplatin iv (AUC6 Day 1 of a 21-day cycle) for 6 cycles.

Followed by a post-completion phase in which no study treatment was administered

Period Title: Overall Study
Started 81 81
Received Study Treatment 81 75
Entered Maintenance Phase 66 55
Ongoing Study Treatment at Data Cut-off 11 0
Completed 25 [1] 26 [2]
Not Completed 56 55
Reason Not Completed
Death             54             47
Withdrawal by Subject             2             6
Allocated treatment but did not take it             0             1
Lost to Follow-up             0             1
[1]
Completed is ongoing study at DCO (Data cut-off),either on-treatment or in survival follow-up
[2]
Completed is ongoing study at DCO (Data cut-off), either on-treatment or in survival follow-up
Arm/Group Title Olaparib/Carboplatin AUC4/Paclitaxel Carboplatin AUC6/Paclitaxel Total
Hide Arm/Group Description

Olaparib orally (po) (200mg bd Days 1-10 of a 21-day cycle) in combination with paclitaxel intravenous (iv) (175 mg/m2 Day 1 of a 21-day cycle) and carboplatin iv (AUC4 Day 1 of a 21-day cycle) for at least 4 cycles.

Followed by olaparib monotherapy maintenance (400mg bd continuous dosing)

Paclitaxel iv (175mg/m2 Day 1 of a 21-day cycle) and carboplatin iv (AUC6 Day 1 of a 21-day cycle) for 6 cycles.

Followed by a post-completion phase in which no study treatment was administered

Total of all reporting groups
Overall Number of Baseline Participants 81 81 162
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 81 participants 81 participants 162 participants
57.9  (10.0) 59.0  (10.7) 58.5  (10.3)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 81 participants 81 participants 162 participants
< 50 15 17 32
≥ 50 - < 65 45 40 85
≥ 65 21 24 45
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 81 participants 81 participants 162 participants
Female
81
 100.0%
81
 100.0%
162
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Number of prior platinum-containing treatment lines  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 81 participants 81 participants 162 participants
1 58 53 111
>1 23 28 51
Time to disease progression on completion of the previous platinum therapy  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 81 participants 81 participants 162 participants
PD > 6 to ≤ 12 months after completion 39 40 79
PD >12 months after completion 42 41 83
1.Primary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS (based on independent central review) was defined as the time from randomisation until objective disease progression as defined by Response Evaluation Criteria In Solid Tumours (RECIST) v1.1 (≥20% increase in the sum of the diameters of target lesions from minimum, clinically significant progression in non-target lesions or the presence of a new lesion) or death (by any cause in the absence of progression).
Time Frame Radiologic scans performed at weeks 9 and 18 (+/-1 week) and every 12 weeks thereafter relative to the date of randomisation until the primary analysis (approximately 20 months)
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Hide Analysis Population Description
Full Analysis Set (FAS)
Arm/Group Title Olaparib/Carboplatin AUC4/Paclitaxel Carboplatin AUC6/Paclitaxel
Hide Arm/Group Description:

Olaparib orally (po) (200mg bd Days 1-10 of a 21-day cycle) in combination with paclitaxel intravenous (iv) (175 mg/m2 Day 1 of a 21-day cycle) and carboplatin iv (AUC4 Day 1 of a 21-day cycle) for at least 4 cycles.

Followed by olaparib monotherapy maintenance (400mg bd continuous dosing)

Paclitaxel iv (175mg/m2 Day 1 of a 21-day cycle) and carboplatin iv (AUC6 Day 1 of a 21-day cycle) for 6 cycles.

Followed by a post-completion phase in which no study treatment was administered

Overall Number of Participants Analyzed 81 81
Median (95% Confidence Interval)
Unit of Measure: months
12.2
(9.7 to 15.0)
9.6
(9.1 to 9.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib/Carboplatin AUC4/Paclitaxel, Carboplatin AUC6/Paclitaxel
Comments The null hypothesis for all efficacy analyses in this study is that there is no difference in treatment effects between olaparib in combination with carboplatin/paclitaxel compared with carboplatin/paclitaxel alone.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0012
Comments The use of a one-sided 10% significance level test will be used to assess the statistical significance of the analyses of PFS.
Method Log Rank
Comments Stratified by number of prior platinum treatment lines (1 or >1) and time to progression following previous platinum therapy (>6 to ≤12 vs >12 months)
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
0.34 to 0.77
Estimation Comments A hazard ratio of < 1 favours olaparib.
2.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from randomisation until death by any cause. Patients who had not died at the time of analysis were censored at the last date the patient was known to be alive.
Time Frame Following disease progression, patients will be contacted every 12 weeks to assess survival status until the final analysis (approximately 50 months)
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Hide Analysis Population Description
FAS
Arm/Group Title Olaparib/Carboplatin AUC4/Paclitaxel Carboplatin AUC6/Paclitaxel
Hide Arm/Group Description:

Olaparib orally (po) (200mg bd Days 1-10 of a 21-day cycle) in combination with paclitaxel intravenous (iv) (175 mg/m2 Day 1 of a 21-day cycle) and carboplatin iv (AUC4 Day 1 of a 21-day cycle) for at least 4 cycles.

Followed by olaparib monotherapy maintenance (400mg bd continuous dosing)

Paclitaxel iv (175mg/m2 Day 1 of a 21-day cycle) and carboplatin iv (AUC6 Day 1 of a 21-day cycle) for 6 cycles.

Followed by a post-completion phase in which no study treatment was administered

Overall Number of Participants Analyzed 81 81
Measure Type: Number
Unit of Measure: Participants (Number of deaths)
54 47
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olaparib/Carboplatin AUC4/Paclitaxel, Carboplatin AUC6/Paclitaxel
Comments The null hypothesis for all efficacy analyses in this study is that there is no difference in treatment effects between olaparib in combination with carboplatin/paclitaxel compared with carboplatin/paclitaxel alone.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4379
Comments Two sided
Method Log Rank
Comments Stratified by number of prior platinum treatment lines (1 or >1) and time to progression following previous platinum therapy (>6 to ≤12 vs >12 months)
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.17
Confidence Interval (2-Sided) 95%
0.79 to 1.73
Estimation Comments A hazard ratio < 1 favours favours olaparib.
3.Secondary Outcome
Title Percentage Change in Tumour Size
Hide Description The total tumour size was defined as the sum of the longest diameters of the target lesions. At week 9, the percentage change in tumour size was calculated as [(week 9 sum of target lesions - baseline sum of target lesions)/baseline sum of target lesions]*100 for each patient. Imputations were used for missing data where possible.
Time Frame Week 9 (+/- 1 week)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS, but including only patients with target lesions at baseline
Arm/Group Title Olaparib/Carboplatin AUC4/Paclitaxel Carboplatin AUC6/Paclitaxel
Hide Arm/Group Description:

Olaparib orally (po) (200mg bd Days 1-10 of a 21-day cycle) in combination with paclitaxel intravenous (iv) (175 mg/m2 Day 1 of a 21-day cycle) and carboplatin iv (AUC4 Day 1 of a 21-day cycle) for at least 4 cycles.

Followed by olaparib monotherapy maintenance (400mg bd continuous dosing)

Paclitaxel iv (175mg/m2 Day 1 of a 21-day cycle) and carboplatin iv (AUC6 Day 1 of a 21-day cycle) for 6 cycles.

Followed by a post-completion phase in which no study treatment was administered

Overall Number of Participants Analyzed 70 67
Least Squares Mean (Standard Error)
Unit of Measure: Percentage change
-38.4  (4.0) -39.1  (4.0)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Olaparib/Carboplatin AUC4/Paclitaxel Carboplatin AUC6/Paclitaxel
Hide Arm/Group Description

Olaparib orally (po) (200mg bd Days 1-10 of a 21-day cycle) in combination with paclitaxel intravenous (iv) (175 mg/m2 Day 1 of a 21-day cycle) and carboplatin iv (AUC4 Day 1 of a 21-day cycle) for at least 4 cycles.

Followed by olaparib monotherapy maintenance (400mg bd continuous dosing)

Paclitaxel iv (175mg/m2 Day 1 of a 21-day cycle) and carboplatin iv (AUC6 Day 1 of a 21-day cycle) for 6 cycles.

Followed by a post-completion phase in which no study treatment was administered

All-Cause Mortality
Olaparib/Carboplatin AUC4/Paclitaxel Carboplatin AUC6/Paclitaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Olaparib/Carboplatin AUC4/Paclitaxel Carboplatin AUC6/Paclitaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   17/81 (20.99%)   19/75 (25.33%) 
Blood and lymphatic system disorders     
Anaemia  1  0/81 (0.00%)  2/75 (2.67%) 
Febrile Neutropenia  1  3/81 (3.70%)  1/75 (1.33%) 
Lymphadenitis  1  0/81 (0.00%)  1/75 (1.33%) 
Neutropenia  1  3/81 (3.70%)  1/75 (1.33%) 
Cardiac disorders     
Angina Unstable  1  0/81 (0.00%)  1/75 (1.33%) 
Eye disorders     
Entropion  1  0/81 (0.00%)  1/75 (1.33%) 
Eyelid Ptosis  1  0/81 (0.00%)  1/75 (1.33%) 
Gastrointestinal disorders     
Abdominal Pain  1  0/81 (0.00%)  2/75 (2.67%) 
Abdominal Pain Upper  1  1/81 (1.23%)  0/75 (0.00%) 
Gastrointestinal Obstruction  1  0/81 (0.00%)  1/75 (1.33%) 
Gastrointestinal Pain  1  0/81 (0.00%)  1/75 (1.33%) 
Small Intestinal Obstruction  1  1/81 (1.23%)  0/75 (0.00%) 
Vomiting  1  1/81 (1.23%)  0/75 (0.00%) 
General disorders     
Pyrexia  1  1/81 (1.23%)  0/75 (0.00%) 
Hepatobiliary disorders     
Hepatitis Acute  1  0/81 (0.00%)  1/75 (1.33%) 
Immune system disorders     
Anaphylactic Reaction  1  0/81 (0.00%)  1/75 (1.33%) 
Anaphylactic Shock  1  0/81 (0.00%)  1/75 (1.33%) 
Drug Hypersensitivity  1  2/81 (2.47%)  2/75 (2.67%) 
Infections and infestations     
Cytomegalovirus Infection  1  1/81 (1.23%)  0/75 (0.00%) 
Enterocolitis Infectious  1  1/81 (1.23%)  0/75 (0.00%) 
Muscle Abscess  1  0/81 (0.00%)  1/75 (1.33%) 
Urinary Tract Infection  1  1/81 (1.23%)  0/75 (0.00%) 
Injury, poisoning and procedural complications     
Cervical Vertebral Fracture  1  0/81 (0.00%)  1/75 (1.33%) 
Femoral Neck Fracture  1  2/81 (2.47%)  0/75 (0.00%) 
Investigations     
Coagulation Time Prolonged  1  0/81 (0.00%)  1/75 (1.33%) 
Metabolism and nutrition disorders     
Hypokalaemia  1  0/81 (0.00%)  1/75 (1.33%) 
Hyponatraemia  1  0/81 (0.00%)  1/75 (1.33%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Myelodysplastic Syndrome  1  1/81 (1.23%)  0/75 (0.00%) 
Nervous system disorders     
Polyneuropathy  1  0/81 (0.00%)  1/75 (1.33%) 
Respiratory, thoracic and mediastinal disorders     
Pleural Effusion  1  1/81 (1.23%)  1/75 (1.33%) 
Pulmonary Embolism  1  1/81 (1.23%)  0/75 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Olaparib/Carboplatin AUC4/Paclitaxel Carboplatin AUC6/Paclitaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   81/81 (100.00%)   72/75 (96.00%) 
Blood and lymphatic system disorders     
Anaemia  1  25/81 (30.86%)  17/75 (22.67%) 
Leukopenia  1  12/81 (14.81%)  10/75 (13.33%) 
Neutropenia  1  41/81 (50.62%)  32/75 (42.67%) 
Thrombocytopenia  1  20/81 (24.69%)  14/75 (18.67%) 
Ear and labyrinth disorders     
Tinnitus  1  5/81 (6.17%)  4/75 (5.33%) 
Eye disorders     
Vision Blurred  1  4/81 (4.94%)  4/75 (5.33%) 
Gastrointestinal disorders     
Abdominal Discomfort  1  6/81 (7.41%)  2/75 (2.67%) 
Abdominal Distension  1  7/81 (8.64%)  6/75 (8.00%) 
Abdominal Pain  1  25/81 (30.86%)  16/75 (21.33%) 
Abdominal Pain Lower  1  3/81 (3.70%)  4/75 (5.33%) 
Abdominal Pain Upper  1  16/81 (19.75%)  8/75 (10.67%) 
Constipation  1  30/81 (37.04%)  24/75 (32.00%) 
Diarrhoea  1  37/81 (45.68%)  24/75 (32.00%) 
Dyspepsia  1  24/81 (29.63%)  9/75 (12.00%) 
Flatulence  1  4/81 (4.94%)  4/75 (5.33%) 
Nausea  1  65/81 (80.25%)  44/75 (58.67%) 
Stomatitis  1  17/81 (20.99%)  8/75 (10.67%) 
Vomiting  1  33/81 (40.74%)  21/75 (28.00%) 
General disorders     
Asthenia  1  13/81 (16.05%)  7/75 (9.33%) 
Fatigue  1  52/81 (64.20%)  43/75 (57.33%) 
Mucosal Inflammation  1  4/81 (4.94%)  5/75 (6.67%) 
Oedema Peripheral  1  9/81 (11.11%)  5/75 (6.67%) 
Pyrexia  1  10/81 (12.35%)  6/75 (8.00%) 
Immune system disorders     
Drug Hypersensitivity  1  15/81 (18.52%)  13/75 (17.33%) 
Infections and infestations     
Influenza  1  5/81 (6.17%)  0/75 (0.00%) 
Nasopharyngitis  1  16/81 (19.75%)  5/75 (6.67%) 
Urinary Tract Infection  1  7/81 (8.64%)  4/75 (5.33%) 
Investigations     
White Blood Cell Count Decreased  1  2/81 (2.47%)  5/75 (6.67%) 
Metabolism and nutrition disorders     
Decreased Appetite  1  27/81 (33.33%)  19/75 (25.33%) 
Hyperglycaemia  1  2/81 (2.47%)  4/75 (5.33%) 
Hypomagnesaemia  1  8/81 (9.88%)  7/75 (9.33%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  24/81 (29.63%)  21/75 (28.00%) 
Back Pain  1  11/81 (13.58%)  9/75 (12.00%) 
Bone Pain  1  8/81 (9.88%)  7/75 (9.33%) 
Muscle Spasms  1  9/81 (11.11%)  2/75 (2.67%) 
Musculoskeletal Chest Pain  1  4/81 (4.94%)  4/75 (5.33%) 
Musculoskeletal Pain  1  9/81 (11.11%)  5/75 (6.67%) 
Myalgia  1  27/81 (33.33%)  18/75 (24.00%) 
Pain In Extremity  1  15/81 (18.52%)  13/75 (17.33%) 
Nervous system disorders     
Dizziness  1  16/81 (19.75%)  7/75 (9.33%) 
Dysgeusia  1  23/81 (28.40%)  12/75 (16.00%) 
Headache  1  32/81 (39.51%)  8/75 (10.67%) 
Hypoaesthesia  1  4/81 (4.94%)  5/75 (6.67%) 
Neuropathy Peripheral  1  26/81 (32.10%)  17/75 (22.67%) 
Paraesthesia  1  11/81 (13.58%)  9/75 (12.00%) 
Peripheral Sensory Neuropathy  1  17/81 (20.99%)  21/75 (28.00%) 
Psychiatric disorders     
Anxiety  1  6/81 (7.41%)  4/75 (5.33%) 
Insomnia  1  19/81 (23.46%)  12/75 (16.00%) 
Renal and urinary disorders     
Dysuria  1  2/81 (2.47%)  6/75 (8.00%) 
Reproductive system and breast disorders     
Vaginal Discharge  1  2/81 (2.47%)  6/75 (8.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  20/81 (24.69%)  13/75 (17.33%) 
Dyspnoea  1  15/81 (18.52%)  6/75 (8.00%) 
Dyspnoea Exertional  1  4/81 (4.94%)  5/75 (6.67%) 
Epistaxis  1  5/81 (6.17%)  3/75 (4.00%) 
Oropharyngeal Pain  1  11/81 (13.58%)  7/75 (9.33%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  60/81 (74.07%)  44/75 (58.67%) 
Erythema  1  5/81 (6.17%)  2/75 (2.67%) 
Pruritus  1  10/81 (12.35%)  7/75 (9.33%) 
Rash  1  14/81 (17.28%)  11/75 (14.67%) 
Vascular disorders     
Flushing  1  7/81 (8.64%)  4/75 (5.33%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.0
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Gerard Lynch
Organization: AstraZeneca
EMail: aztrial_results_posting@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01081951    
Other Study ID Numbers: D0810C00041
First Submitted: February 26, 2010
First Posted: March 5, 2010
Results First Submitted: November 12, 2012
Results First Posted: December 10, 2012
Last Update Posted: September 14, 2020