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

Ovarian Neoplasms Clinical Trial

— ICEBERG 3  

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00628251
• Other study ID #: D0810C00012
• Status: Completed
• Phase: Phase 2
• Start date: July 30, 2008
• Est. completion date: September 19, 2018

Study information

• Verified date: November 2019
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 97
• Est. completion date: September 19, 2018
• Est. primary completion date: September 15, 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

• Advanced ovarian cancer with positive BRCA1 or BRCA2 status

• Progressive or recurrent disease after platinum-based chemotherapy

• Measurable disease by RECIST

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Neoplasms

Intervention

Drug:
• AZD2281
400mg Oral twice daily
• Liposomal Doxorubicin
50mg/m2 Monthly Intravenous
• AZD2281
200mg oral twice daily

Locations

Country	Name	City	State
Australia	Research Site	East Melbourne
Australia	Research Site	Melbourne, Parkville
Australia	Research Site	Randwick
Belgium	Research Site	Leuven
Germany	Research Site	Köln
Germany	Research Site	München
Israel	Research Site	Haifa
Israel	Research Site	Ramat Gan
Israel	Research Site	Tel Aviv
Poland	Research Site	Szczecin
Spain	Research Site	Barcelona
Spain	Research Site	Hospitalet deLlobregat
Sweden	Research Site	Lund
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Sutton
United States	Research Site	Boca Raton	Florida
United States	Research Site	Boston	Massachusetts
United States	Research Site	Houston	Texas
United States	Research Site	Los Angeles	California
United States	Research Site	New York	New York
United States	Research Site	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Germany,  Israel,  Poland,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	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	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.	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Secondary	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	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Secondary	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.)	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Secondary	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	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Secondary	Best Percentage Change From Baseline in CA-125 Levels	Best percentage change in cancer antigen 125 (CA-125) levels	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Secondary	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.	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Secondary	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	At the time of the cut-off for the final analysis of overall survival (30 April 2010)
Secondary	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.	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Secondary	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.	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Secondary	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.	At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)

External Links

•   CSR_Synopsis_D0810C00012.pdf