Study to Assess the Efficacy and Safety of a PARP Inhibitor for the Treatment of BRCA-positive Advanced Breast Cancer (ICEBERG 1)

This study is ongoing, but not recruiting participants.
KuDOS Pharmaceuticals Limited
Information provided by (Responsible Party):
AstraZeneca Identifier:
First received: June 27, 2007
Last updated: July 23, 2015
Last verified: July 2015

The purpose of the study is to see if the drug KU 0059436 (olaparib) is effective and well tolerated in treating patients with measurable BRCA1- or BRCA2-positive advanced breast cancer and for whom no curative therapeutic option exists.

Condition Intervention Phase
Breast Neoplasms
Drug: KU-0059436 (AZD2281) (PARP inhibitor)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Open-label, Non-comparative, International, Multicentre Study to Assess the Efficacy and Safety of KU 0059436 (Olaparib) Given Orally Twice Daily in Patients With Advanced BRCA1 or BRCA2 Associated Breast Cancer

Resource links provided by NLM:

Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Confirmed Objective Tumour Response (According to RECIST Criteria) [ Time Frame: Baseline, every 8 also at study termination or initiation of confounding anti-cancer therapy. Up to 2 years. ] [ Designated as safety issue: No ]
    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease from baseline in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary Outcome Measures:
  • Duration of Response to Olaparib [ Time Frame: Time from response (CR or PR) to progression per RECIST criteria ] [ Designated as safety issue: No ]
  • The Clinical Benefit Rate (CBR) [ Time Frame: End of study ] [ Designated as safety issue: No ]
    The Clinical Benefit Rate (CBR) is defined as the percentage of patients with a RECIST tumour response of confirmed CR, PR or stable disease (SD) for ≥8 weeks +/- 1 week visit window.

  • Best Percent Change in Tumour Size [ Time Frame: End of study ] [ Designated as safety issue: No ]
    The tumour size is defined as the sum of the longest diameters as measured among all target lesions.

  • Progression-Free Survival (PFS) [ Time Frame: End of study ] [ Designated as safety issue: No ]
    PFS is defined as the time from first dose to the earlier date of radiologic progression (as per RECIST criteria) or death by any cause in the absence of objective progression. Those patients who were withdrawn from the study without disease progression were regarded as censored at their last evaluable RECIST assessment. Where patients had not progressed at the termination of the study, they were also regarded as censored at their last evaluable RECIST assessment.

  • Change From Baseline in ECOG Performance Status: Improvement Rate [ Time Frame: At cycle 7 day 1 (ie, after completing 6 cycles of treatment) ] [ Designated as safety issue: No ]
    The change in ECOG performance status was defined as improved (meaning the ECOG score is less than the baseline value), no change (ECOG is same as at baseline), worsened (ECOG score is greater than the baseline value) or missing (the ECOG score is missing or was not recorded at baseline). If no measurement was recorded at Cycle 1 Day 1, the change was calculated in relation to the last recorded ECOG value prior to Day 1.

Enrollment: 81
Study Start Date: June 2007
Estimated Study Completion Date: December 2015
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: KU-0059436 (AZD2281) 100 mg BID
KU-0059436 (AZD2281) 100 mg BID
Drug: KU-0059436 (AZD2281) (PARP inhibitor)
Other Name: Olaparib
Experimental: KU-0059436 (AZD2281) 400 mg BID
KU-0059436 (AZD2281) 400 mg BID
Drug: KU-0059436 (AZD2281) (PARP inhibitor)


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Advanced breast cancer with positive BRCA1 or BRCA2 status
  • Failed at least one prior chemotherapy
  • In investigators opinion, no curative standard therapy exists
  • Measurable disease

Exclusion Criteria:

  • 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 identifier: NCT00494234

United States, California
Research Site
Los Angeles, California, 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, Pennsylvania
Research Site
Philadelphia, Pennsylvania, United States
United States, Texas
Research Site
Dallas, Texas, United States
Research Site
East Melbourne, Australia
Research Site
Randwick, Australia
Research Site
Köln, Germany
Research Site
Lund, Sweden
United Kingdom
Research Site
Cambridge, United Kingdom
Research Site
London, United Kingdom
Research Site
Manchester, United Kingdom
Sponsors and Collaborators
KuDOS Pharmaceuticals Limited
Study Director: James Carmichael, BSc, MBChB, MD, FRCP KuDOS Pharmaceuticals Limited
Principal Investigator: Andrew Tutt, PhD MRCP FRCR Guy's and St Thomas's NHS Foundation Trust, London, UK
  More Information

Additional Information:
No publications provided by AstraZeneca

Additional publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: AstraZeneca Identifier: NCT00494234     History of Changes
Other Study ID Numbers: KU36-44, D0810C00008
Study First Received: June 27, 2007
Results First Received: January 16, 2015
Last Updated: July 23, 2015
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: Spanish Agency of Medicines

Keywords provided by AstraZeneca:
Advanced breast cancer
Poly(ADP ribose) polymerases
AZD2281,KU-0059436 (olaparib)
BRCA1 protein
BRCA2 protein

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms by Site
Skin Diseases processed this record on October 06, 2015