Dose-finding Study Comparing Efficacy and Safety of a PARP Inhibitor Against Doxil in BRCA+ve Advanced Ovarian Cancer (ICEBERG 3)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00628251
First received: February 26, 2008
Last updated: April 27, 2016
Last verified: April 2016
Results First Received: January 14, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Ovarian Neoplasms
Interventions: Drug: AZD2281
Drug: Liposomal Doxorubicin

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The first patient was enrolled on 30 July 2008 and the last patient was enrolled on 3 March 2009 (for initial treatment). Patients were enrolled at 25 centres in 9 countries: Australia, Belgium, Germany, Israel, Poland, Spain, Sweden, UK and USA.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
One hundred and twenty-five (125) women with advanced breast cancer gene (BRCA) 1- or 2- associated ovarian cancer who had failed previous platinum-based chemotherapy were planned to receive olaparib 200 mg bd, olaparib 400 mg bd or liposomal doxorubicin 50 mg/m2 intravenously in a 1:1:1 ratio. Of these 97 were randomised.

Reporting Groups
  Description
Olaparib 200 mg bd Olaparib (AZD2281) 200 mg oral capsules twice daily
Olaparib 400 mg bd Olaparib (AZD2281) 400 mg oral capsules twice daily
Liposomal Doxorubicin Liposomal doxorubicin 50 mg/m2 intravenously every 4 weeks

Participant Flow for 2 periods

Period 1:   Randomised Part
    Olaparib 200 mg bd     Olaparib 400 mg bd     Liposomal Doxorubicin  
STARTED     32 [1]   32 [1]   33 [1]
COMPLETED     32 [2]   32 [2]   25 [3]
NOT COMPLETED     0     0     8  
Did not receive cross over treatment                 0                 0                 8  
[1] Patients randomised
[2] Patients who received olaparib treatment
[3] Patients who received olaparib (crossed over). 1 of 33 did not receive Liposomal Doxorubicin.

Period 2:   Cross-over/ Continuation of Olaparib
    Olaparib 200 mg bd     Olaparib 400 mg bd     Liposomal Doxorubicin  
STARTED     32 [1]   32 [1]   25 [2]
COMPLETED     5 [3]   6 [3]   8 [4]
NOT COMPLETED     27     26     17  
Adverse Event                 1                 2                 0  
Condition under investigation worsened                 24                 21                 13  
Withdrawal by Subject                 1                 2                 4  
Unknown                 1                 1                 0  
[1] Patients who received treatment
[2] Patients who crossed over from Liposomal doxorubicin to Olaparib 400 mg bd
[3] Ongoing initial study treatment at primary data cut-off
[4] Patients ongoing crossover treatment



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Olaparib 200 mg bd Olaparib (AZD2281) 200 mg oral capsules twice daily
Olaparib 400 mg bd Olaparib (AZD2281) 400 mg oral capsules twice daily
Liposomal Doxorubicin Liposomal doxorubicin 50 mg/m2 intravenously every 4 weeks
Total Total of all reporting groups

Baseline Measures
    Olaparib 200 mg bd     Olaparib 400 mg bd     Liposomal Doxorubicin     Total  
Number of Participants  
[units: participants]
  32     32     33     97  
Age  
[units: Years]
Mean (Standard Deviation)
  57.2  (8.53)     53.8  (8.77)     54.3  (9.32)     55.5  (8.92)  
Gender  
[units: Participants]
       
Female     32     32     33     97  
Male     0     0     0     0  
Race/Ethnicity, Customized [1]
[units: Participants]
       
African-Caribbean     0     0     1     1  
Ashkenazi Jewish     8     10     11     29  
Sephardic Jewish     0     0     2     2  
Not applicable     20     21     19     60  
Other     4     1     0     5  
BRCA status  
[units: Participants]
       
Deleterious BRCA1 mutation     26     28     27     81  
Deleterious BRCA2 mutation     6     4     6     16  
[1] Jewish ethnicity



  Outcome Measures
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1.  Primary:   Progression Free Survival (PFS) (According to Response Evaluation Criteria in Solid Tumours [RECIST])   [ Time Frame: Tumour assessment was to be assessed at screening, every 8 weeks during the study and at the withdrawal visit, up to 56 weeks. (Data cut-off for primary analysis of PFS: 15 September 2009) ]

2.  Secondary:   Objective Response Rate (ORR) (According to Response Evaluation Criteria in Solid Tumours - RECIST)   [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]

3.  Secondary:   Duration of Response   [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]

4.  Secondary:   Best Percentage Change in Tumour Size   [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]

5.  Secondary:   Best Percentage Change From Baseline in CA-125 Levels   [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]

6.  Secondary:   Confirmed RECIST Response and/or CA-125 Response   [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]

7.  Secondary:   Disease Control Rate   [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]

8.  Secondary:   Overall Survival (OS)   [ Time Frame: At the time of the cut-off for the final analysis of overall survival (30 April 2010) ]

9.  Secondary:   Best Quality of Life (QoL) Response for Trial Outcome Index (TOI)   [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]

10.  Secondary:   Best QoL Response for Total Functional Analysis of Cancer Therapy - Ovarian (FACT-O)   [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]

11.  Secondary:   Best QoL Response for FACT-O Symptom Index (FOSI)   [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The AEs reported include all events up to the OS data cut-off. After the PFS data cut-off, AEs were only collected for the olaparib and cross-over groups. The safety profile of these 2 groups at OS was consistent with that at the time of PFS.


  More Information
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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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Gerard Lynch
Organization: AstraZeneca
e-mail: ClinicalTrialTransparency@astrazeneca.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00628251     History of Changes
Other Study ID Numbers: D0810C00012
Study First Received: February 26, 2008
Results First Received: January 14, 2015
Last Updated: April 27, 2016
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Australia: Department of Health and Ageing Therapeutic Goods Administration
Germany: Federal Institute for Drugs and Medical Devices
Sweden: Medical Products Agency
Spain: Ministry of Health
Israel: Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Belgium: Federal Agency for Medicinal Products and Health Products