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Study to Assess the Efficacy and Safety of a PARP Inhibitor for the Treatment of BRCA-positive Advanced Ovarian Cancer (ICEBERG 2)

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ClinicalTrials.gov Identifier: NCT00494442
Recruitment Status : Completed
First Posted : June 29, 2007
Results First Posted : January 26, 2015
Last Update Posted : August 1, 2018
Sponsor:
Collaborator:
KuDOS Pharmaceuticals Limited
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Ovarian Neoplasm
Intervention Drug: KU-0059436 (AZD2281)(PARP inhibitor)
Enrollment 58
Recruitment Details The first patient was enrolled on June 11, 2007 and efficacy and safety data were collected up to the data cut-off of March 17, 2009. Patients were enrolled at 12 centres in 5 countries: Australia, Germany, Spain, Sweden and the USA.
Pre-assignment Details Two cohorts of women with Breast Cancer gene 1 (BRCA1)- or BRCA2-associated ovarian cancer who had failed at least one prior chemotherapy in the advanced/metastatic setting, were planned to receive olaparib 100 mg bd (n= up to 24) or 400 mg bd (n= up to 40). Enrolment to 2 cohorts was sequential with the 400 mg bd cohort being recruited first.
Arm/Group Title Olaparib 100 mg bd Olaparib 400 mg bd
Hide Arm/Group Description olaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice daily olaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily
Period Title: Overall Study
Started 24 [1] 33 [1]
Completed 7 [2] 17 [2]
Not Completed 17 16
Reason Not Completed
Death             1             1
Lack of Efficacy             16             10
Adverse Event             0             2
Physician Decision             0             1
Non-compliance             0             1
Intercurrent illness             0             1
[1]
Patients received treatment
[2]
Patients completed the full study schedule (168 days treatment)
Arm/Group Title Olaparib 100 mg bd Olaparib 400 mg bd Total
Hide Arm/Group Description olaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice daily olaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily Total of all reporting groups
Overall Number of Baseline Participants 24 33 57
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants 33 participants 57 participants
55.6  (8.02) 56.8  (10.49) 56  (9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 33 participants 57 participants
Female
24
 100.0%
33
 100.0%
57
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
BRCA mutation   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 33 participants 57 participants
BRCA1
19
  79.2%
21
  63.6%
40
  70.2%
BRCA2
5
  20.8%
12
  36.4%
17
  29.8%
[1]
Measure Description: BRCA1 or BRCA2 mutations known to cause loss of gene function (clinical deleterious or suspected deleterious mutations).
1.Primary Outcome
Title Confirmed Objective Tumour Response (According to Response Evaluation Criteria In Solid Tumors (RECIST)
Hide Description Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease from baseline in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame Baseline, every 8 also at study termination or initiation of confounding anti-cancer therapy.
Hide Outcome Measure Data
Hide Analysis Population Description
PP Analysis Set (includes all enrolled patients who complete the trial schedule and medication regime without any major deviations to the protocol - this is the main analysis population, with ITT used to confirm)
Arm/Group Title Olaparib 100 mg bd Olaparib 400 mg bd
Hide Arm/Group Description:
olaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice daily
olaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily
Overall Number of Participants Analyzed 24 33
Measure Type: Number
Unit of Measure: Participants
PP Analysis Set Number Analyzed 22 participants 31 participants
3 11
ITT Analysis Set Number Analyzed 24 participants 33 participants
3 11
2.Secondary Outcome
Title Clinical Benefit (CB)
Hide Description Clinical Benefit (CB) is defined as the percentage of patients with a RECIST tumour response of confirmed complete response, partial response or stable disease for ≥8 weeks)
Time Frame End of study
Hide Outcome Measure Data
Hide Analysis Population Description
PP Analysis Set (includes all enrolled patients who complete the trial schedule and medication regime without any major deviations to the protocol - this is the main analysis population, with ITT used to confirm)
Arm/Group Title Olaparib 100 mg bd Olaparib 400 mg bd
Hide Arm/Group Description:
olaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice daily
olaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily
Overall Number of Participants Analyzed 24 33
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
45.5
(26.9 to 65.3)
71.0
(53.4 to 83.9)
3.Secondary Outcome
Title Duration of Response
Hide Description Duration of response to olaparib
Time Frame End of study
Hide Outcome Measure Data
Hide Analysis Population Description
PP Analysis Set (includes all enrolled patients who complete the trial schedule and medication regime without any major deviations to the protocol - this is the main analysis population, with ITT used to confirm
Arm/Group Title Olaparib 100 mg bd Olaparib 400 mg bd
Hide Arm/Group Description:
olaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice daily
olaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily
Overall Number of Participants Analyzed 24 33
Median (Full Range)
Unit of Measure: Days
242
(169 to 288)
301
(126 to 506)
4.Secondary Outcome
Title Best Percentage Change in Tumour Size
Hide Description The best % change (reduction) from baseline in tumour size (defined as the sum of the longest diameters as measured among all target lesions).
Time Frame End of study
Hide Outcome Measure Data
Hide Analysis Population Description
PP Analysis Set (includes all enrolled patients who complete the trial schedule and medication regime without any major deviations to the protocol - this is the main analysis population, with ITT used to confirm
Arm/Group Title Olaparib 100 mg bd Olaparib 400 mg bd
Hide Arm/Group Description:
olaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice daily
olaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily
Overall Number of Participants Analyzed 24 33
Median (Full Range)
Unit of Measure: Percent change
-5.1
(-85.7 to 66.1)
-25.8
(-100.0 to 150.0)
5.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide Description Progression-Free Survival (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.
Time Frame End of study
Hide Outcome Measure Data
Hide Analysis Population Description
PP Analysis Set (includes all enrolled patients who complete the trial schedule and medication regime without any major deviations to the protocol - this is the main analysis population, with ITT used to confirm
Arm/Group Title Olaparib 100 mg bd Olaparib 400 mg bd
Hide Arm/Group Description:
olaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice daily
olaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily
Overall Number of Participants Analyzed 24 33
Median (95% Confidence Interval)
Unit of Measure: Days
62.5
(56 to 113)
226
(105 to 338)
Time Frame From baseline, every visit until 30 days after last dose.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Olaparib 100 mg bd Olaparib 400 mg bd
Hide Arm/Group Description olaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice daily olaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily
All-Cause Mortality
Olaparib 100 mg bd Olaparib 400 mg bd
Affected / at Risk (%) Affected / at Risk (%)
Total   10/24 (41.67%)   11/33 (33.33%) 
Hide Serious Adverse Events
Olaparib 100 mg bd Olaparib 400 mg bd
Affected / at Risk (%) Affected / at Risk (%)
Total   7/24 (29.17%)   12/33 (36.36%) 
Blood and lymphatic system disorders     
Neutropenia  1  1/24 (4.17%)  1/33 (3.03%) 
Anaemia  1  0/24 (0.00%)  1/33 (3.03%) 
Cardiac disorders     
Cardiac Failure Congestive  1  1/24 (4.17%)  0/33 (0.00%) 
Gastrointestinal disorders     
Intestinal Obstruction  1  0/24 (0.00%)  2/33 (6.06%) 
Nausea  1  1/24 (4.17%)  2/33 (6.06%) 
Vomiting  1  1/24 (4.17%)  2/33 (6.06%) 
Abdominal Pain  1  1/24 (4.17%)  0/33 (0.00%) 
Large Intestinal Obstruction  1  1/24 (4.17%)  1/33 (3.03%) 
Gastrointestinal Obstruction  1  0/24 (0.00%)  1/33 (3.03%) 
Ileus  1  0/24 (0.00%)  1/33 (3.03%) 
Intestinal Perforation  1  0/24 (0.00%)  1/33 (3.03%) 
Small Intestinal Obstruction  1  0/24 (0.00%)  1/33 (3.03%) 
General disorders     
Oedema Peripheral  1  0/24 (0.00%)  1/33 (3.03%) 
Hepatobiliary disorders     
Bile Duct Stone  1  0/24 (0.00%)  1/33 (3.03%) 
Infections and infestations     
Pneumonia  1  0/24 (0.00%)  1/33 (3.03%) 
Injury, poisoning and procedural complications     
Humerus Fracture  1  0/24 (0.00%)  1/33 (3.03%) 
Blood Pressure Increased  1  1/24 (4.17%)  0/33 (0.00%) 
Metabolism and nutrition disorders     
Hyponatraemia  1  1/24 (4.17%)  0/33 (0.00%) 
Dehydration  1  0/24 (0.00%)  1/33 (3.03%) 
Hypokalaemia  1  0/24 (0.00%)  1/33 (3.03%) 
Nervous system disorders     
Encephalopathy  1  1/24 (4.17%)  0/33 (0.00%) 
Convulsion  1  0/24 (0.00%)  1/33 (3.03%) 
Psychiatric disorders     
Mental Status Changes  1  1/24 (4.17%)  0/33 (0.00%) 
Renal and urinary disorders     
Renal Failure  1  1/24 (4.17%)  0/33 (0.00%) 
Renal Failure Acute  1  0/24 (0.00%)  1/33 (3.03%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary Embolism  1  1/24 (4.17%)  0/33 (0.00%) 
Respiratory Failure  1  1/24 (4.17%)  0/33 (0.00%) 
Vascular disorders     
Deep Vein Thrombosis  1  0/24 (0.00%)  1/33 (3.03%) 
1
Term from vocabulary, MedDRA 10.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Olaparib 100 mg bd Olaparib 400 mg bd
Affected / at Risk (%) Affected / at Risk (%)
Total   23/24 (95.83%)   33/33 (100.00%) 
Blood and lymphatic system disorders     
Anaemia  1  3/24 (12.50%)  7/33 (21.21%) 
Lymphopenia  1  2/24 (8.33%)  0/33 (0.00%) 
Thrombocytopenia  1  3/24 (12.50%)  1/33 (3.03%) 
Neutropenia  1  2/24 (8.33%)  3/33 (9.09%) 
Gastrointestinal disorders     
Nausea  1  15/24 (62.50%)  21/33 (63.64%) 
Diarrhoea  1  7/24 (29.17%)  12/33 (36.36%) 
Abdominal Pain  1  4/24 (16.67%)  9/33 (27.27%) 
Vomiting  1  6/24 (25.00%)  11/33 (33.33%) 
Constipation  1  6/24 (25.00%)  4/33 (12.12%) 
Abdominal Distension  1  4/24 (16.67%)  6/33 (18.18%) 
Dyspepsia  1  4/24 (16.67%)  4/33 (12.12%) 
Abdominal Pain Upper  1  3/24 (12.50%)  3/33 (9.09%) 
Abdominal Discomfort  1  1/24 (4.17%)  3/33 (9.09%) 
Abdominal Pain Lower  1  0/24 (0.00%)  3/33 (9.09%) 
Gastrooesophageal Reflux Disease  1  1/24 (4.17%)  3/33 (9.09%) 
Gastrointestinal Pain  1  2/24 (8.33%)  0/33 (0.00%) 
Ascites  1  0/24 (0.00%)  2/33 (6.06%) 
Gastritis  1  0/24 (0.00%)  2/33 (6.06%) 
Rectal Haemorrhage  1  0/24 (0.00%)  2/33 (6.06%) 
Salivary Hypersecretion  1  0/24 (0.00%)  2/33 (6.06%) 
Stomatitis  1  1/24 (4.17%)  2/33 (6.06%) 
Intestinal obstruction  1  0/24 (0.00%)  2/33 (6.06%) 
General disorders     
Fatigue  1  13/24 (54.17%)  17/33 (51.52%) 
Oedema Peripheral  1  1/24 (4.17%)  6/33 (18.18%) 
Pyrexia  1  2/24 (8.33%)  2/33 (6.06%) 
Asthenia  1  0/24 (0.00%)  2/33 (6.06%) 
Infections and infestations     
Urinary Tract Infection  1  5/24 (20.83%)  2/33 (6.06%) 
Upper Respiratory Tract Infection  1  2/24 (8.33%)  3/33 (9.09%) 
Oral Herpes  1  2/24 (8.33%)  0/33 (0.00%) 
Cellulitis  1  0/24 (0.00%)  2/33 (6.06%) 
Herpes Zoster  1  0/24 (0.00%)  2/33 (6.06%) 
Nasopharyngitis  1  0/24 (0.00%)  2/33 (6.06%) 
Sinusitis  1  0/24 (0.00%)  2/33 (6.06%) 
Injury, poisoning and procedural complications     
Contusion  1  1/24 (4.17%)  4/33 (12.12%) 
Investigations     
Waist Circumference Increased  1  4/24 (16.67%)  0/33 (0.00%) 
Haemoglobin Urine  1  3/24 (12.50%)  0/33 (0.00%) 
Blood Urine Present  1  2/24 (8.33%)  0/33 (0.00%) 
Gamma-Glutamyltransferase Increased  1  0/24 (0.00%)  2/33 (6.06%) 
Metabolism and nutrition disorders     
Hypokalaemia  1  2/24 (8.33%)  4/33 (12.12%) 
Hypomagnesaemia  1  1/24 (4.17%)  4/33 (12.12%) 
Anorexia  1  1/24 (4.17%)  3/33 (9.09%) 
Hyperkalaemia  1  2/24 (8.33%)  0/33 (0.00%) 
Decreased Appetite  1  1/24 (4.17%)  2/33 (6.06%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  4/24 (16.67%)  2/33 (6.06%) 
Back Pain  1  4/24 (16.67%)  2/33 (6.06%) 
Muscle Spasms  1  0/24 (0.00%)  4/33 (12.12%) 
Pain In Extremity  1  0/24 (0.00%)  3/33 (9.09%) 
Flank Pain  1  0/24 (0.00%)  2/33 (6.06%) 
Joint Swelling  1  0/24 (0.00%)  2/33 (6.06%) 
Myalgia  1  1/24 (4.17%)  2/33 (6.06%) 
Nervous system disorders     
Headache  1  4/24 (16.67%)  7/33 (21.21%) 
Neuropathy Peripheral  1  4/24 (16.67%)  1/33 (3.03%) 
Dizziness  1  2/24 (8.33%)  3/33 (9.09%) 
Dysgeusia  1  2/24 (8.33%)  1/33 (3.03%) 
Sinus Headache  1  1/24 (4.17%)  2/33 (6.06%) 
Psychiatric disorders     
Insomnia  1  1/24 (4.17%)  4/33 (12.12%) 
Depression  1  2/24 (8.33%)  3/33 (9.09%) 
Anxiety  1  1/24 (4.17%)  2/33 (6.06%) 
Renal and urinary disorders     
Pollakiuria  1  2/24 (8.33%)  0/33 (0.00%) 
Reproductive system and breast disorders     
Pelvic Pain  1  2/24 (8.33%)  2/33 (6.06%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  4/24 (16.67%)  0/33 (0.00%) 
Cough  1  3/24 (12.50%)  1/33 (3.03%) 
Dyspnoea Exertional  1  0/24 (0.00%)  2/33 (6.06%) 
Oropharyngeal Pain  1  1/24 (4.17%)  2/33 (6.06%) 
Skin and subcutaneous tissue disorders     
Rash  1  5/24 (20.83%)  5/33 (15.15%) 
Dry Skin  1  2/24 (8.33%)  1/33 (3.03%) 
1
Term from vocabulary, MedDRA 10.0
Indicates events were collected by systematic assessment
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.
The sponsor can review and comment prior to publication. In order to ensure that the Sponsor will be able to make comments and suggestions where pertinent, material for public dissemination will be submittted to the Sponsor for review at least sixty (60) days prior to submission for publication, public dissemination, or review by a publication committee
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Gerard Lynch
Organization: AstraZeneca
EMail: ClinicalTrialTransparency@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00494442    
Other Study ID Numbers: KU36-58
D0810C00009
First Submitted: June 27, 2007
First Posted: June 29, 2007
Results First Submitted: January 15, 2015
Results First Posted: January 26, 2015
Last Update Posted: August 1, 2018