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Study to Assess the Efficacy and Safety of a PARP Inhibitor for the Treatment of BRCA-positive Advanced Breast Cancer (ICEBERG 1)

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ClinicalTrials.gov Identifier: NCT00494234
Recruitment Status : Active, not recruiting
First Posted : June 29, 2007
Results First Posted : January 26, 2015
Last Update Posted : May 31, 2019
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 Breast Neoplasms
Intervention Drug: KU-0059436 (AZD2281) (PARP inhibitor)
Enrollment 54
Recruitment Details The first patient was enrolled on June 15, 2007 and efficacy and safety data were collected up to the data cut-off of February 27, 2009. Patients were enrolled at 16 centres in 6 countries: Australia, Germany, Spain, Sweden, UK and the USA.
Pre-assignment Details Two cohorts of up to 27 women with BRCA1- or BRCA2-associated breast cancer who had failed at least one prior chemotherapy and/or endocrine therapy in the advanced/metastatic setting, were assigned to receive olaparib 100 mg bd or 400 mg bd. Enrolment into the 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 Full Analysis Set Full Analysis Set
Period Title: Overall Study
Started 27 27
Completed 12 17
Not Completed 15 10
Reason Not Completed
Lack of Efficacy             12             9
Withdrawal by Subject             1             0
Death             2             1
Arm/Group Title AZD2281 100 mg AZD2281 400 mg Total
Hide Arm/Group Description [Not Specified] [Not Specified] Total of all reporting groups
Overall Number of Baseline Participants 27 27 54
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 27 participants 27 participants 54 participants
44.7  (11.99) 44.7  (9.55) 44.7  (10.74)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 27 participants 27 participants 54 participants
<35 years 7 3 10
>=35 - <50 years 11 18 29
>=50 - <65 years 6 5 11
>=65 years 3 1 4
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 27 participants 54 participants
Female
27
 100.0%
27
 100.0%
54
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 27 participants 27 participants 54 participants
Asian 1 1 2
Black or african american 1 0 1
White 25 26 51
1.Primary Outcome
Title Confirmed Objective Tumour Response (According to RECIST Criteria)
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. Up to 2 years.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Olaparib 100 mg bd Olaparib 400 mg bd
Hide Arm/Group Description:
Per Protocol Set
Per Protocol Set
Overall Number of Participants Analyzed 24 26
Measure Type: Number
Unit of Measure: Participants
6 11
2.Secondary Outcome
Title Duration of Response to Olaparib
Hide Description [Not Specified]
Time Frame Time from response (CR or PR) to progression per RECIST criteria
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Per protocol
Arm/Group Title Olaparib 100 mg bd Olaparib 400 mg bd
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Number of responders
Number of responders
Overall Number of Participants Analyzed 6 11
Median (Full Range)
Unit of Measure: Days
140.5
(55 to 175)
144.0
(92 to 393)
3.Secondary Outcome
Title The Clinical Benefit Rate (CBR)
Hide Description The Clinical Benefit Rate (CBR) is defined as the percentage of patients with a RECIST tumour response of confirmed CR, PR or stable disease (SD) for ≥8 weeks +/- 1 week visit window.
Time Frame End of study
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Hide Analysis Population Description
Per protocol
Arm/Group Title Olaparib 100 mg bd Olaparib 400 mg bd
Hide Arm/Group Description:
Per Protocol Set
Per Protocol Set
Overall Number of Participants Analyzed 24 26
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
62.5
(42.7 to 78.8)
84.6
(66.5 to 93.9)
4.Secondary Outcome
Title Best Percent Change in Tumour Size
Hide Description The tumour size is 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
[Not Specified]
Arm/Group Title Olaparib 100 mg bd Olaparib 400 mg bd
Hide Arm/Group Description:
Per Protocol Set
Per Protocol Set
Overall Number of Participants Analyzed 24 26
Mean (95% Confidence Interval)
Unit of Measure: Percent change in tumour size
1.15
(-27.97 to 30.26)
-36.06
(-49.98 to -22.14)
5.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide Description 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 patients who were withdrawn from the study without disease progression were regarded as censored at their last evaluable RECIST assessment. Where patients had not progressed at the termination of the study, they were also regarded as censored at their last evaluable RECIST assessment.
Time Frame End of study
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Olaparib 100 mg bd Olaparib 400 mg bd
Hide Arm/Group Description:
Per Protocol Set
Per Protocol Set
Overall Number of Participants Analyzed 24 26
Median (95% Confidence Interval)
Unit of Measure: Days
122
(67 to 167)
193
(140 to 226)
6.Secondary Outcome
Title Change From Baseline in ECOG Performance Status: Improvement Rate
Hide Description The change in ECOG performance status was defined as improved (meaning the ECOG score is less than the baseline value), no change (ECOG is same as at baseline), worsened (ECOG score is greater than the baseline value) or missing (the ECOG 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 At cycle 7 day 1 (ie, after completing 6 cycles of treatment)
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Olaparib 100 mg bd Olaparib 400 mg bd
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Patients who compled 6 cycles of treatment
Patients who compled 6 cycles of treatment
Overall Number of Participants Analyzed 11 15
Measure Type: Number
Unit of Measure: Participants with an improvement in ECOG
1 6
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title AZD2281 100 mg AZD2281 400 mg
Hide Arm/Group Description [Not Specified] [Not Specified]
All-Cause Mortality
AZD2281 100 mg AZD2281 400 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
AZD2281 100 mg AZD2281 400 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/27 (18.52%)      9/27 (33.33%)    
Blood and lymphatic system disorders     
ANAEMIA  1  1/27 (3.70%)  1 1/27 (3.70%)  1
Cardiac disorders     
ANGINA PECTORIS  1  0/27 (0.00%)  0 1/27 (3.70%)  1
Gastrointestinal disorders     
NAUSEA  1  0/27 (0.00%)  0 3/27 (11.11%)  3
VOMITING  1  0/27 (0.00%)  0 2/27 (7.41%)  2
Injury, poisoning and procedural complications     
ALLERGIC TRANSFUSION REACTION  1  0/27 (0.00%)  0 1/27 (3.70%)  1
Investigations     
HAEMOGLOBIN DECREASED  1  0/27 (0.00%)  0 1/27 (3.70%)  1
Musculoskeletal and connective tissue disorders     
MUSCULOSKELETAL CHEST PAIN  1  1/27 (3.70%)  1 0/27 (0.00%)  0
Nervous system disorders     
CEREBRAL HAEMORRHAGE  1  1/27 (3.70%)  1 0/27 (0.00%)  0
CONVULSION  1  1/27 (3.70%)  1 0/27 (0.00%)  0
Renal and urinary disorders     
RENAL FAILURE ACUTE  1  1/27 (3.70%)  1 0/27 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
DYSPNOEA  1  2/27 (7.41%)  2 0/27 (0.00%)  0
PLEURAL EFFUSION  1  1/27 (3.70%)  1 0/27 (0.00%)  0
PNEUMOTHORAX  1  0/27 (0.00%)  0 1/27 (3.70%)  1
RESPIRATORY DISORDER  1  1/27 (3.70%)  1 0/27 (0.00%)  0
Skin and subcutaneous tissue disorders     
PURPURA  1  0/27 (0.00%)  0 1/27 (3.70%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
AZD2281 100 mg AZD2281 400 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   27/27 (100.00%)      26/27 (96.30%)    
Blood and lymphatic system disorders     
ANAEMIA  1  3/27 (11.11%)  3 5/27 (18.52%)  5
NEUTROPENIA  1  0/27 (0.00%)  0 2/27 (7.41%)  2
Gastrointestinal disorders     
ABDOMINAL PAIN  1  2/27 (7.41%)  2 5/27 (18.52%)  5
ABDOMINAL PAIN LOWER  1  2/27 (7.41%)  2 0/27 (0.00%)  0
ABDOMINAL PAIN UPPER  1  0/27 (0.00%)  0 2/27 (7.41%)  3
CONSTIPATION  1  8/27 (29.63%)  8 6/27 (22.22%)  6
DIARRHOEA  1  4/27 (14.81%)  5 8/27 (29.63%)  10
DYSPEPSIA  1  2/27 (7.41%)  2 5/27 (18.52%)  5
FLATULENCE  1  0/27 (0.00%)  0 2/27 (7.41%)  3
GASTROOESOPHAGEAL REFLUX DISEASE  1  1/27 (3.70%)  1 2/27 (7.41%)  2
NAUSEA  1  15/27 (55.56%)  19 14/27 (51.85%)  17
STOMATITIS  1  3/27 (11.11%)  3 1/27 (3.70%)  1
TOOTHACHE  1  2/27 (7.41%)  2 1/27 (3.70%)  1
VOMITING  1  6/27 (22.22%)  8 10/27 (37.04%)  16
General disorders     
ASTHENIA  1  0/27 (0.00%)  0 2/27 (7.41%)  2
CHEST PAIN  1  1/27 (3.70%)  1 2/27 (7.41%)  2
FATIGUE  1  17/27 (62.96%)  19 19/27 (70.37%)  25
INFLUENZA LIKE ILLNESS  1  0/27 (0.00%)  0 2/27 (7.41%)  2
OEDEMA PERIPHERAL  1  4/27 (14.81%)  4 6/27 (22.22%)  6
PYREXIA  1  2/27 (7.41%)  2 3/27 (11.11%)  3
Infections and infestations     
BRONCHITIS  1  0/27 (0.00%)  0 2/27 (7.41%)  2
NASOPHARYNGITIS  1  0/27 (0.00%)  0 2/27 (7.41%)  4
ORAL CANDIDIASIS  1  2/27 (7.41%)  2 1/27 (3.70%)  1
SINUSITIS  1  2/27 (7.41%)  2 0/27 (0.00%)  0
UPPER RESPIRATORY TRACT INFECTION  1  4/27 (14.81%)  5 2/27 (7.41%)  3
URINARY TRACT INFECTION  1  2/27 (7.41%)  2 3/27 (11.11%)  3
Investigations     
ALANINE AMINOTRANSFERASE INCREASED  1  2/27 (7.41%)  2 0/27 (0.00%)  0
ASPARTATE AMINOTRANSFERASE INCREASED  1  3/27 (11.11%)  3 0/27 (0.00%)  0
WEIGHT INCREASED  1  0/27 (0.00%)  0 3/27 (11.11%)  3
Metabolism and nutrition disorders     
ANOREXIA  1  5/27 (18.52%)  5 3/27 (11.11%)  3
HYPOKALAEMIA  1  0/27 (0.00%)  0 2/27 (7.41%)  2
Musculoskeletal and connective tissue disorders     
ARTHRALGIA  1  6/27 (22.22%)  7 4/27 (14.81%)  4
BACK PAIN  1  6/27 (22.22%)  6 1/27 (3.70%)  1
BONE PAIN  1  1/27 (3.70%)  2 2/27 (7.41%)  2
MUSCULAR WEAKNESS  1  2/27 (7.41%)  2 0/27 (0.00%)  0
MUSCULOSKELETAL CHEST PAIN  1  2/27 (7.41%)  2 2/27 (7.41%)  3
PAIN IN EXTREMITY  1  7/27 (25.93%)  7 2/27 (7.41%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
CANCER PAIN  1  4/27 (14.81%)  4 1/27 (3.70%)  1
Nervous system disorders     
HEADACHE  1  6/27 (22.22%)  9 10/27 (37.04%)  23
HYPOAESTHESIA  1  0/27 (0.00%)  0 2/27 (7.41%)  2
LETHARGY  1  0/27 (0.00%)  0 2/27 (7.41%)  2
MIGRAINE  1  1/27 (3.70%)  1 3/27 (11.11%)  5
PERIPHERAL SENSORY NEUROPATHY  1  3/27 (11.11%)  3 0/27 (0.00%)  0
Psychiatric disorders     
DEPRESSION  1  3/27 (11.11%)  3 1/27 (3.70%)  1
INSOMNIA  1  7/27 (25.93%)  7 2/27 (7.41%)  2
Renal and urinary disorders     
URINARY TRACT PAIN  1  2/27 (7.41%)  2 1/27 (3.70%)  1
Reproductive system and breast disorders     
PELVIC PAIN  1  2/27 (7.41%)  2 0/27 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
COUGH  1  8/27 (29.63%)  8 4/27 (14.81%)  5
DYSPNOEA  1  9/27 (33.33%)  9 1/27 (3.70%)  1
DYSPNOEA EXERTIONAL  1  0/27 (0.00%)  0 2/27 (7.41%)  2
PLEURAL EFFUSION  1  2/27 (7.41%)  2 0/27 (0.00%)  0
Skin and subcutaneous tissue disorders     
RASH  1  1/27 (3.70%)  1 2/27 (7.41%)  2
SKIN LESION  1  0/27 (0.00%)  0 2/27 (7.41%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.0
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: Clinical Trial Transparency
Organization: AstraZeneca
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00494234     History of Changes
Other Study ID Numbers: KU36-44
D0810C00008
First Submitted: June 27, 2007
First Posted: June 29, 2007
Results First Submitted: January 16, 2015
Results First Posted: January 26, 2015
Last Update Posted: May 31, 2019