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Investigate the Safety and Tolerability of Olaparib Tablet in Japanese Patients With Advanced Solid Malignancies

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ClinicalTrials.gov Identifier: NCT01813474
Recruitment Status : Completed
First Posted : March 19, 2013
Results First Posted : December 12, 2017
Last Update Posted : January 16, 2018
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Cancer
Advanced Solid Malignancies
Intervention Drug: olaparib
Enrollment 23
Recruitment Details First patient enrolled on 25 March 2013. Last patient enrolled on 31 October 2013. Data cut off on 31 July 2014.
Pre-assignment Details A total of 28 participants gave informed consent to join this study. Five participants were screen failures so that 23 participants were assigned and received study treatment
Arm/Group Title 200 mg Bid, Dose Escalation Part 300 mg Bid, Dose Escalation Part 300 mg Bid, Expansion Part
Hide Arm/Group Description Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part Olaparib table 300 mg bid, 600 mg/day, dose escalation part Olaparib tablet 300 mg bid, 600 mg/day, expansion part
Period Title: Overall Study
Started 4 7 12
Completed 1 [1] 0 1 [1]
Not Completed 3 7 11
Reason Not Completed
Withdrawal by Subject             0             0             1
Adverse Event             1             1             0
Lack of Efficacy             2             6             9
Death             0             0             1
[1]
ongoing study at final data cut off
Arm/Group Title 200 mg Bid, Dose Escalation Part 300 mg Bid, Dose Escalation Part 300 mg Bid, Expansion Part Total
Hide Arm/Group Description Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part Olaparib table 300 mg bid, 600 mg/day, dose escalation part Olaparib tablet 300 mg bid, 600 mg/day, expansion part Total of all reporting groups
Overall Number of Baseline Participants 4 7 12 23
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4 participants 7 participants 12 participants 23 participants
42.0  (8.68) 55.4  (8.98) 57.3  (12.43) 54.1  (11.94)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Sex Number Analyzed 4 participants 7 participants 12 participants 23 participants
Female
4
 100.0%
4
  57.1%
7
  58.3%
15
  65.2%
Male
0
   0.0%
3
  42.9%
5
  41.7%
8
  34.8%
Primary tumour location  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 7 participants 12 participants 23 participants
Breast
1
  25.0%
1
  14.3%
3
  25.0%
5
  21.7%
Colorectal
0
   0.0%
0
   0.0%
1
   8.3%
1
   4.3%
Lung
0
   0.0%
1
  14.3%
2
  16.7%
3
  13.0%
Peritoneum
0
   0.0%
0
   0.0%
1
   8.3%
1
   4.3%
Pancreas
0
   0.0%
1
  14.3%
0
   0.0%
1
   4.3%
Ovary
0
   0.0%
2
  28.6%
2
  16.7%
4
  17.4%
Uterus
1
  25.0%
1
  14.3%
0
   0.0%
2
   8.7%
Cervix
2
  50.0%
0
   0.0%
0
   0.0%
2
   8.7%
Colon
0
   0.0%
0
   0.0%
1
   8.3%
1
   4.3%
Gastric Antrum
0
   0.0%
0
   0.0%
1
   8.3%
1
   4.3%
Other
0
   0.0%
1
  14.3%
1
   8.3%
2
   8.7%
1.Primary Outcome
Title Number of Participants With Adverse Events
Hide Description An adverse event is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. This was recorded if it happend from the start dose to 30 days after the last of study drug.
Time Frame From the start dose to 30 days after the last dose of study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 200 mg Bid, Dose Escalation Part 300 mg Bid, Dose Escalation Part 300 mg Bid, Expansion Part
Hide Arm/Group Description:
Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part
Olaparib table 300 mg bid, 600 mg/day, dose escalation part
Olaparib tablet 300 mg bid, 600 mg/day, expansion part
Overall Number of Participants Analyzed 4 7 12
Measure Type: Number
Unit of Measure: Participants
At least 1 Adverse Events (AE) 4 7 10
At least 1 AE of CTCAE Grade 3 or higher 1 3 1
At least 1 Serious Adverse Events (SAE) 1 0 0
2.Secondary Outcome
Title Number of Participants With Dose Limiting Toxicities
Hide Description Dose Limiting Toxicities were defined as study specific events that is determined to be possibly or probably related to olaparib (as determined by the investigator) and occurring during the first cycle of treatment (28 days after the first dose), irrespective of whether the toxicity resolved.
Time Frame From the start dose to 28 days after the first dose of study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All patients in only the dose escalation part who received olaparib and completed the safety follow-up through the dose-limiting toxicity (DLT) evaluation period (28 days), or who experienced a DLT.
Arm/Group Title 200 mg Bid, Dose Escalation Part 300 mg Bid, Dose Escalation Part
Hide Arm/Group Description:
Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part
Olaparib tablet 300 mg bid, 600 mg/day, dose escalation part
Overall Number of Participants Analyzed 3 6
Measure Type: Number
Unit of Measure: Participants
0 0
3.Secondary Outcome
Title Cmax Following Single Dosing
Hide Description [Not Specified]
Time Frame Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours at post-dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Dose escalation part only
Arm/Group Title 200 mg Bid, Dose Escalation Part 300 mg Bid, Dose Escalation Part
Hide Arm/Group Description:
Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part
Olaparib table 300 mg bid, 600 mg/day, dose escalation part
Overall Number of Participants Analyzed 4 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: μg/mL
6.697
(95.69%)
7.743
(34.76%)
4.Secondary Outcome
Title Cmax Following Multiple Dosing
Hide Description [Not Specified]
Time Frame Day 15: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours at post-dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Dose escalation part only. Two participants (1 in 200 mg bid and 1 in 300 mg bid) had no PK data due to early discontinuation prior to Day 15.
Arm/Group Title 200 mg Bid, Dose Escalation Part 300 mg Bid, Dose Escalation Part
Hide Arm/Group Description:
Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part
Olaparib table 300 mg bid, 600 mg/day, dose escalation part
Overall Number of Participants Analyzed 3 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: μg/mL
7.668
(46.93%)
8.434
(35.05%)
5.Secondary Outcome
Title Tmax Following Single Dosing
Hide Description [Not Specified]
Time Frame Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours at post-dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Dose escalation part only
Arm/Group Title 200 mg Bid, Dose Escalation Part 300 mg Bid, Dose Escalation Part
Hide Arm/Group Description:
Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part
Olaparib table 300 mg bid, 600 mg/day, dose escalation part
Overall Number of Participants Analyzed 4 7
Median (Full Range)
Unit of Measure: hour
2.00
(1.00 to 3.00)
1.98
(1.00 to 3.00)
6.Secondary Outcome
Title Tmax Following Multiple Dosing
Hide Description [Not Specified]
Time Frame Day 15: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours at post-dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Dose escalation part only. Two participants (1 in 200 mg bid and 1 in 300 mg bid) had no PK data due to early discontinuation prior to Day 15.
Arm/Group Title 200 mg Bid, Dose Escalation Part 300 mg Bid, Dose Escalation Part
Hide Arm/Group Description:
Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part
Olaparib table 300 mg bid, 600 mg/day, dose escalation part
Overall Number of Participants Analyzed 3 6
Median (Full Range)
Unit of Measure: hour
1.50
(1.00 to 3.00)
3.00
(1.50 to 3.93)
7.Secondary Outcome
Title AUC Following Single Dosing
Hide Description [Not Specified]
Time Frame Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours at post-dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Dose escalation part only. One participant in 200 mg bid had no AUC data because AUC was not calculable for this participant.
Arm/Group Title 200 mg Bid, Dose Escalation Part 300 mg Bid, Dose Escalation Part
Hide Arm/Group Description:
Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part
Olaparib table 300 mg bid, 600 mg/day, dose escalation part
Overall Number of Participants Analyzed 3 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: μg*h/mL
61.97
(473.4%)
46.21
(64.64%)
8.Secondary Outcome
Title AUC at Steady State Following Multiple Dosing
Hide Description [Not Specified]
Time Frame Day 15: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours at post-dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Dose escalation part only. Two participants (1 in 200 mg bid and 1 in 300 mg bid) had no PK data due to early discontinuation prior to Day 15.
Arm/Group Title 200 mg Bid, Dose Escalation Part 300 mg Bid, Dose Escalation Part
Hide Arm/Group Description:
Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part
Olaparib table 300 mg bid, 600 mg/day, dose escalation part
Overall Number of Participants Analyzed 3 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: μg*h/mL
36.50
(71.94%)
52.34
(68.17%)
Time Frame Through treatment and 30-day follow-up period, an average of about 4 months.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 200 mg Bid, Dose Escalation Part 300 mg Bid, Dose Escalation Part 300 mg Bid, Expansion Part
Hide Arm/Group Description Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part Olaparib table 300 mg bid, 600 mg/day, dose escalation part Olaparib tablet 300 mg bid, 600 mg/day, expansion part
All-Cause Mortality
200 mg Bid, Dose Escalation Part 300 mg Bid, Dose Escalation Part 300 mg Bid, Expansion Part
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
200 mg Bid, Dose Escalation Part 300 mg Bid, Dose Escalation Part 300 mg Bid, Expansion Part
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/4 (25.00%)      0/7 (0.00%)      0/12 (0.00%)    
Gastrointestinal disorders       
Ileus * 1  1/4 (25.00%)  1 0/7 (0.00%)  0 0/12 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 16.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
200 mg Bid, Dose Escalation Part 300 mg Bid, Dose Escalation Part 300 mg Bid, Expansion Part
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/4 (100.00%)      7/7 (100.00%)      10/12 (83.33%)    
Blood and lymphatic system disorders       
Anaemia * 1  0/4 (0.00%)  4/7 (57.14%)  2/12 (16.67%) 
Neutropenia * 1  0/4 (0.00%)  1/7 (14.29%)  0/12 (0.00%) 
Eye disorders       
Erythema of eyelid * 1  0/4 (0.00%)  1/7 (14.29%)  0/12 (0.00%) 
Eye pruritus * 1  0/4 (0.00%)  1/7 (14.29%)  0/12 (0.00%) 
Gastrointestinal disorders       
Abdominal pain upper * 1  0/4 (0.00%)  1/7 (14.29%)  1/12 (8.33%) 
Constipation * 1  0/4 (0.00%)  2/7 (28.57%)  4/12 (33.33%) 
Diarrhoea * 1  0/4 (0.00%)  2/7 (28.57%)  2/12 (16.67%) 
Duodenitis * 1  0/4 (0.00%)  1/7 (14.29%)  0/12 (0.00%) 
Dyspepsia * 1  0/4 (0.00%)  2/7 (28.57%)  1/12 (8.33%) 
Gastritis * 1  0/4 (0.00%)  0/7 (0.00%)  1/12 (8.33%) 
Nausea * 1  1/4 (25.00%)  6/7 (85.71%)  3/12 (25.00%) 
Stomatitis * 1  0/4 (0.00%)  1/7 (14.29%)  0/12 (0.00%) 
Toothache * 1  1/4 (25.00%)  0/7 (0.00%)  0/12 (0.00%) 
Vomiting * 1  0/4 (0.00%)  1/7 (14.29%)  1/12 (8.33%) 
General disorders       
Fatigue * 1  0/4 (0.00%)  1/7 (14.29%)  2/12 (16.67%) 
Malaise * 1  0/4 (0.00%)  2/7 (28.57%)  2/12 (16.67%) 
Oedema * 1  0/4 (0.00%)  1/7 (14.29%)  0/12 (0.00%) 
Pyrexia * 1  0/4 (0.00%)  1/7 (14.29%)  0/12 (0.00%) 
Hepatobiliary disorders       
Hepatic function abnormal * 1  0/4 (0.00%)  0/7 (0.00%)  1/12 (8.33%) 
Infections and infestations       
Nasopharyngitis * 1  1/4 (25.00%)  0/7 (0.00%)  1/12 (8.33%) 
Paronychia * 1  0/4 (0.00%)  1/7 (14.29%)  0/12 (0.00%) 
Pneumonia * 1  0/4 (0.00%)  0/7 (0.00%)  1/12 (8.33%) 
Pyelonephritis * 1  1/4 (25.00%)  0/7 (0.00%)  0/12 (0.00%) 
Upper respiratory tract infection * 1  0/4 (0.00%)  0/7 (0.00%)  1/12 (8.33%) 
Injury, poisoning and procedural complications       
Contusion * 1  0/4 (0.00%)  0/7 (0.00%)  1/12 (8.33%) 
Procedural pain * 1  0/4 (0.00%)  1/7 (14.29%)  0/12 (0.00%) 
Investigations       
Alanine aminotransferase increased * 1  0/4 (0.00%)  1/7 (14.29%)  1/12 (8.33%) 
Aspartate aminotransferase increased * 1  0/4 (0.00%)  1/7 (14.29%)  1/12 (8.33%) 
Blood creatinine increased * 1  0/4 (0.00%)  1/7 (14.29%)  1/12 (8.33%) 
Grip strength decreased * 1  0/4 (0.00%)  1/7 (14.29%)  0/12 (0.00%) 
Lymphocyte count decreased * 1  0/4 (0.00%)  1/7 (14.29%)  0/12 (0.00%) 
Neutrophil count decreased * 1  0/4 (0.00%)  2/7 (28.57%)  2/12 (16.67%) 
Platelet count decreased * 1  0/4 (0.00%)  1/7 (14.29%)  0/12 (0.00%) 
White blood cell count decreased * 1  0/4 (0.00%)  3/7 (42.86%)  2/12 (16.67%) 
Metabolism and nutrition disorders       
Decreased appetite * 1  0/4 (0.00%)  4/7 (57.14%)  3/12 (25.00%) 
Hypoglycaemia * 1  0/4 (0.00%)  1/7 (14.29%)  0/12 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  0/4 (0.00%)  0/7 (0.00%)  1/12 (8.33%) 
Back pain * 1  1/4 (25.00%)  0/7 (0.00%)  0/12 (0.00%) 
Myalgia * 1  0/4 (0.00%)  1/7 (14.29%)  0/12 (0.00%) 
Pain in extremity * 1  0/4 (0.00%)  1/7 (14.29%)  0/12 (0.00%) 
Nervous system disorders       
Dizziness * 1  0/4 (0.00%)  1/7 (14.29%)  0/12 (0.00%) 
Dysgeusia * 1  0/4 (0.00%)  1/7 (14.29%)  0/12 (0.00%) 
Headache * 1  1/4 (25.00%)  0/7 (0.00%)  0/12 (0.00%) 
Psychiatric disorders       
Anxiety * 1  0/4 (0.00%)  1/7 (14.29%)  0/12 (0.00%) 
Renal and urinary disorders       
Proteinuria * 1  0/4 (0.00%)  2/7 (28.57%)  0/12 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough * 1  0/4 (0.00%)  1/7 (14.29%)  0/12 (0.00%) 
Dysaesthesia pharynx * 1  1/4 (25.00%)  1/7 (14.29%)  0/12 (0.00%) 
Dyspnoea * 1  0/4 (0.00%)  1/7 (14.29%)  0/12 (0.00%) 
Skin and subcutaneous tissue disorders       
Palmar-plantar erythrodysaesthesia syndrome * 1  0/4 (0.00%)  1/7 (14.29%)  0/12 (0.00%) 
Pruritus * 1  0/4 (0.00%)  1/7 (14.29%)  0/12 (0.00%) 
Rash maculo-papular * 1  0/4 (0.00%)  0/7 (0.00%)  1/12 (8.33%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 16.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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
Name/Title: Medical Director
Organization: AstraZeneca
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01813474     History of Changes
Other Study ID Numbers: D081BC00001
First Submitted: March 15, 2013
First Posted: March 19, 2013
Results First Submitted: July 6, 2017
Results First Posted: December 12, 2017
Last Update Posted: January 16, 2018