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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00628251




Registration number
NCT00628251
Ethics application status
Date submitted
26/02/2008
Date registered
5/03/2008
Date last updated
5/12/2019

Titles & IDs
Public title
Dose-finding Study Comparing Efficacy and Safety of a PARP Inhibitor Against Doxil in BRCA+ve Advanced Ovarian Cancer
Scientific title
A Phase II, Open-Label, Randomised, Comparative, International Multicentre Study to Assess the Safety and Efficacy of Different Doses of AZD2281 Given Orally Twice Daily Versus Intravenous Liposomal Doxorubicin Given Monthly in Patients With Advanced BRCA1- or BRCA2-Associated Ovarian Cancer Who Have Failed Previous Platinum-based Chemotherapy
Secondary ID [1] 0 0
D0810C00012
Universal Trial Number (UTN)
Trial acronym
ICEBERG 3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ovarian Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - AZD2281
Treatment: Drugs - Liposomal Doxorubicin
Treatment: Drugs - AZD2281

Experimental: 1 - AZD2281 Oral 200 mg BID

Active Comparator: 2 - Liposomal Doxorubicin

Experimental: 3 - AZD2281 Oral 400 mg BID


Treatment: Drugs: AZD2281
400mg Oral twice daily

Treatment: Drugs: Liposomal Doxorubicin
50mg/m2 Monthly Intravenous

Treatment: Drugs: AZD2281
200mg oral twice daily

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) - PFS was defined as the time to progression from the date of randomisation until the date of radiological assessment of progression per RECIST criteria or death (by any cause in the absence of progression)
Timepoint [1] 0 0
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)
Secondary outcome [1] 0 0
Objective Response Rate (ORR) - ORR was defined according to RECIST. Complete response (CR) or partial response - (PR)- 30% decrease Patients with a best RECIST response of CR or PR had to have a confirmed response at least 28 days later.
Timepoint [1] 0 0
At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Secondary outcome [2] 0 0
Disease Control Rate - The number of patients with confirmed CR (disappearance of all target lesions) or PR (30% decrease in the sum of the longest diameter of target lesions ) or SD ( small changes ) >4 months, divided by the number of randomised patients
Timepoint [2] 0 0
At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Secondary outcome [3] 0 0
Overall Duration of Response - The duration of response was defined as time (months) from initial assessment of PR/CR until earliest date of objective progression or death. (Values may be underestimated as some patients had not progressed at final analysis so true duration is likely to be greater than that in database.)
Timepoint [3] 0 0
At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Secondary outcome [4] 0 0
Best Percentage Change in Tumour Size - The percentage change (reduction) from baseline in the sum of the lengths of the longest diameter (LD) of the RECIST target lesions were objectively documented, regardless of whether the patient was still taking study medication
Timepoint [4] 0 0
At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Secondary outcome [5] 0 0
Best Percentage Change From Baseline in CA-125 Levels - Best percentage change in cancer antigen 125 (CA-125) levels
Timepoint [5] 0 0
At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Secondary outcome [6] 0 0
Confirmed RECIST Response and/or CA-125 Response - The percentage of patients reporting a RECIST confirmed response and/or a CA-125 response (in the absence of progression). A CA-125 response was defined as a confirmed greater or equal to 50% reduction in CA-125.
Timepoint [6] 0 0
At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Secondary outcome [7] 0 0
Overall Survival (OS) - OS was defined as time from randomisation to date of death from any cause. Patients who had not died at time of analysis were censored at last date they were known to be alive. Median OS was not calculable for olaparib groups due to an insufficient number of deaths so the percentage of participants who died are shown along with 95% confidence intervals
Timepoint [7] 0 0
At the time of the cut-off for the final analysis of overall survival (30 April 2010)
Secondary outcome [8] 0 0
Best Quality of Life (QoL) Response for Trial Outcome Index (TOI) - Best HRQoL response using the TOI endpoint. Improvement was defined as a change from baseline of greater than or equal to +7. The TOI score ranges from 0-100.
Timepoint [8] 0 0
At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Secondary outcome [9] 0 0
Best QoL Response for Total Functional Analysis of Cancer Therapy - Ovarian (FACT-O) - Best HRQoL response using the total FACT-O endpoint. Improvement was defined as a change from baseline of greater than or equal to +9.
Timepoint [9] 0 0
At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Secondary outcome [10] 0 0
Best QoL Response for FACT-O Symptom Index (FOSI) - Best HRQoL response using the FOSI endpoint. Improvement was defined as a change from baseline of greater than or equal to +3.
Timepoint [10] 0 0
At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)

Eligibility
Key inclusion criteria
- Advanced ovarian cancer with positive BRCA1 or BRCA2 status

- Progressive or recurrent disease after platinum-based chemotherapy

- Measurable disease by RECIST
Minimum age
18 Years
Maximum age
130 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Previous anthracycline treatment

- Brain metastases

- Less than 28 days since last treatment used to treat the disease

- Considered a poor medical risk due to a serious uncontrolled disorder

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - East Melbourne
Recruitment hospital [2] 0 0
Research Site - Melbourne, Parkville
Recruitment hospital [3] 0 0
Research Site - Randwick
Recruitment postcode(s) [1] 0 0
3002 - East Melbourne
Recruitment postcode(s) [2] 0 0
VIC 3050 - Melbourne, Parkville
Recruitment postcode(s) [3] 0 0
2031 - Randwick
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
Belgium
State/province [6] 0 0
Leuven
Country [7] 0 0
Germany
State/province [7] 0 0
Köln
Country [8] 0 0
Germany
State/province [8] 0 0
München
Country [9] 0 0
Israel
State/province [9] 0 0
Haifa
Country [10] 0 0
Israel
State/province [10] 0 0
Ramat Gan
Country [11] 0 0
Israel
State/province [11] 0 0
Tel Aviv
Country [12] 0 0
Poland
State/province [12] 0 0
Szczecin
Country [13] 0 0
Spain
State/province [13] 0 0
Barcelona
Country [14] 0 0
Spain
State/province [14] 0 0
Hospitalet deLlobregat
Country [15] 0 0
Sweden
State/province [15] 0 0
Lund
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Cambridge
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Edinburgh
Country [18] 0 0
United Kingdom
State/province [18] 0 0
London
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Manchester
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of the study is to compare the efficacy and safety of 2 doses of drug AZD2281
against liposomal doxorubicin to see which is effective and well tolerated in treating
patients with measurable BRCA1- or BRCA2-positive advanced ovarian cancer and who have failed
previous platinum therapy.
Trial website
https://clinicaltrials.gov/show/NCT00628251
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jane Robertson, BSc, MBCHB, MD
Address 0 0
AstraZeneca
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications