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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: August 24, 2016
Last verified: August 2016
  Purpose
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.

Condition Intervention Phase
Ovarian Neoplasms
Drug: AZD2281
Drug: Liposomal Doxorubicin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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)


Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.)

  • 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) ] [ Designated as safety issue: No ]
    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

  • 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) ] [ Designated as safety issue: No ]
    Best percentage change in cancer antigen 125 (CA-125) levels

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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

  • Overall Survival (OS) [ Time Frame: At the time of the cut-off for the final analysis of overall survival (30 April 2010) ] [ Designated as safety issue: No ]
    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

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    Best HRQoL response using the total FACT-O endpoint. Improvement was defined as a change from baseline of greater than or equal to +9.

  • 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) ] [ Designated as safety issue: No ]
    Best HRQoL response using the FOSI endpoint. Improvement was defined as a change from baseline of greater than or equal to +3.


Enrollment: 125
Study Start Date: July 2008
Estimated Study Completion Date: December 2016
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
AZD2281 Oral 200 mg BID
Drug: AZD2281
200mg oral twice daily
Active Comparator: 2
Liposomal Doxorubicin
Drug: Liposomal Doxorubicin
50mg/m2 Monthly Intravenous
Other Name: Doxil®
Experimental: 3
AZD2281 Oral 400 mg BID
Drug: AZD2281
400mg Oral twice daily
Other Name: Olaparib

  Eligibility

Ages Eligible for Study:   18 Years to 130 Years   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00628251

Locations
United States, California
Research Site
Los Angeles, California, United States
Research Site
San Francisco, California, United States
United States, Florida
Research Site
Boca Raton, Florida, United States
United States, Massachusetts
Research Site
Boston, Massachusetts, United States
United States, New York
Research Site
New York, New York, United States
United States, Texas
Research Site
Houston, Texas, United States
Australia
Research Site
East Melbourne, Australia
Research Site
Melbourne, Parkville, Australia
Research Site
Randwick, Australia
Belgium
Research Site
Leuven, Belgium
Germany
Research Site
Köln, Germany
Research Site
München, Germany
Israel
Research Site
Haifa, Israel
Research Site
Tel Aviv, Israel
Research Site
Tel-Hashomer, Israel
Poland
Research Site
Szczecin, Poland
Spain
Research Site
Barcelona, Spain
Research Site
Hospitalet deLlobregat, Spain
Sweden
Research Site
Lund, Sweden
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 Kingdom
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Jane Robertson, BSc, MBCHB, MD AstraZeneca
Principal Investigator: Stan Kaye, BSc, MB, FRCP, FRCR, SMedSCi Royal Marsden NHS Foundation Trust
  More Information

Additional Information:
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: August 24, 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

Keywords provided by AstraZeneca:
Advanced ovarian cancer
BRCA1 protein
BRCA2 protein
Poly(ADP ribose) polymerases

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Doxorubicin
Liposomal doxorubicin
Olaparib
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Poly(ADP-ribose) Polymerase Inhibitors

ClinicalTrials.gov processed this record on September 28, 2016