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

November 12, 2019 updated by: AstraZeneca

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

97

Phase

  • Phase 2

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • East Melbourne, Australia, 3002
        • Research Site
      • Melbourne, Parkville, Australia, VIC 3050
        • Research Site
      • Randwick, Australia, 2031
        • Research Site
  • Belgium
      • Leuven, Belgium, 3000
        • Research Site
  • Germany
      • Köln, Germany, 50937
        • Research Site
      • München, Germany, 81377
        • Research Site
  • Israel
      • Haifa, Israel, 31096
        • Research Site
      • Ramat Gan, Israel, 52621
        • Research Site
      • Tel Aviv, Israel, 6423906
        • Research Site
  • Poland
      • Szczecin, Poland, 70-111
        • Research Site
  • Spain
      • Barcelona, Spain, 08035
        • Research Site
      • Hospitalet deLlobregat, Spain, 08907
        • Research Site
  • Sweden
      • Lund, Sweden, 22185
        • Research Site
  • United Kingdom
      • Cambridge, United Kingdom, CB2 0QQ
        • Research Site
      • Edinburgh, United Kingdom, EH4 2XR
        • Research Site
      • London, United Kingdom, SE1 9RT
        • Research Site
      • Manchester, United Kingdom, M20 4BX
        • Research Site
      • Sutton, United Kingdom, SM2 5PT
        • Research Site
  • United States
    • California
      • Los Angeles, California, United States, 90048
        • Research Site
      • San Francisco, California, United States, 94115
        • Research Site
    • Florida
      • Boca Raton, Florida, United States, 33428
        • Research Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Research Site
    • New York
      • New York, New York, United States, 10065
        • Research Site
    • Texas
      • Houston, Texas, United States, 77030
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 130 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
AZD2281 Oral 200 mg BID
Drug: AZD2281
400mg Oral twice daily
Other Names:
  • Olaparib
Drug: AZD2281
200mg oral twice daily
Active Comparator: 2
Liposomal Doxorubicin
Drug: Liposomal Doxorubicin
50mg/m2 Monthly Intravenous
Other Names:
  • Doxil®
Experimental: 3
AZD2281 Oral 400 mg BID
Drug: AZD2281
400mg Oral twice daily
Other Names:
  • Olaparib
Drug: AZD2281
200mg oral twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
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)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
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)
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)
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)
Overall 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)
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)
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)
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)
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)
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)
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)
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)
Overall Survival (OS)
Time Frame: At the time of the cut-off for the final analysis of overall survival (30 April 2010)
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)
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)
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)
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)
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)
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)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Investigators

  • Study Director: Jane Robertson, BSc, MBCHB, MD, AstraZeneca
  • Principal Investigator: Stan Kaye, BSc, MB, FRCP, FRCR, SMedSCi, Royal Marsden NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 30, 2008

Primary Completion (Actual)

September 15, 2009

Study Completion (Actual)

September 19, 2018

Study Registration Dates

First Submitted

February 26, 2008

First Submitted That Met QC Criteria

March 4, 2008

First Posted (Estimate)

March 5, 2008

Study Record Updates

Last Update Posted (Actual)

December 5, 2019

Last Update Submitted That Met QC Criteria

November 12, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D0810C00012

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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