Study to Assess The Efficacy and Safety of a PARP Inhibitor For The Treatment of BRCA-positive Advanced Breast Cancer
ICEBERG 1
A Phase II, Open-label, Non-comparative, International, Multicentre Study to Assess the Efficacy and Safety of KU-0059436 Given Orally Twice Daily in Patients With Advanced BRCA1- or BRCA2-associated Breast Cancer.
3 other identifiers
interventional
54
8 countries
17
Brief Summary
The purpose of the study is to see if the drug KU-0059436 (olaparib) is effective and well tolerated in treating participants with measurable breast cancer gene (BRCA)1- or BRCA2-positive advanced breast cancer and for whom no curative therapeutic option exists.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jun 2007
Longer than P75 for phase_2
17 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 15, 2007
CompletedFirst Submitted
Initial submission to the registry
June 27, 2007
CompletedFirst Posted
Study publicly available on registry
June 29, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 27, 2009
CompletedResults Posted
Study results publicly available
January 26, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
December 21, 2022
CompletedJanuary 19, 2024
January 1, 2024
1.7 years
June 27, 2007
January 16, 2015
January 18, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Confirmed Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
The ORR is the percentage of participants whose best tumor response is either complete response (CR) or partial response (PR), according to the RECIST v1.0 criteria. The CR is defined as disappearance of all target lesions (TLs). The PR is defined as at least a 30% decrease in the sum of longest diameters (LD) taking as reference the baseline sum of LD. Percentage of participants with ORR is reported.
Baseline (Days -28 to 0), Day 1 of Cycle 3, thereafter every alternate cycles until study termination or withdrawal (approximately up to 2 years)
Secondary Outcomes (8)
Duration of Response (DoR) to Olaparib
Baseline (Days -28 to 0), Day 1 of Cycle 3, thereafter every alternate cycles until study termination or withdrawal (approximately up to 2 years)
Clinical Benefit Rate (CBR)
From Day 1 of Cycle 3 through study withdrawal (approximately up to 2 years)
Best Percentage Change in Tumor Size
Baseline (Days -28 to 0) through study withdrawal (approximately up to 2 years)
Progression-free Survival (PFS)
Baseline (Days -28 to 0), Day 1 of Cycle 3, thereafter every alternate cycles until study termination or withdrawal (approximately up to 2 years)
Number of Participants With Improvement in Eastern Co-operative Oncology Group (ECOG) Performance Status Total Score From Baseline
Screening (Days -7 to 0), Day 1 Cycle 7 (ie, after completing 6 cycles of treatment) and study withdrawal (approximately up to 2 years).
- +3 more secondary outcomes
Study Arms (2)
Olaparib 100 mg
EXPERIMENTALParticipants will receive two 50 mg capsules in the morning and two 50 mg capsules in the evening in 28-days cycle until confirmed disease progression, continuous treatment interruption, unacceptable toxicity or any other discontinuation criterion is met.
Olaparib 400 mg
EXPERIMENTALParticipants will receive eight 50 mg capsules in the morning and eight 50 mg capsules in the evening in 28-days cycle until confirmed disease progression, continuous treatment interruption, unacceptable toxicity or any other discontinuation criterion is met.
Interventions
Participants will receive capsules of olaparib orally as stated in arm description.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- KuDOS Pharmaceuticals Limitedcollaborator
Study Sites (17)
Research Site
West Hollywood, California, 90048, United States
Research Site
Boston, Massachusetts, 02115, United States
Research Site
Melbourne, 3000, Australia
Research Site
Randwick, 2031, Australia
Research Site
Duarte, CA, 91010, Canada
Research Site
Cologne, 50937, Germany
Research Site
Kiel, 24105, Germany
Research Site
München, 81675, Germany
Research Site
Tel Aviv, 6423906, Israel
Research Site
Hospitalet deLlobregat, 08907, Spain
Research Site
Madrid, 08035, Spain
Research Site
Lund, 221 85, Sweden
Research Site
Cambridge, CB2 0QQ, United Kingdom
Research Site
Edinburgh, EH4 2XR, United Kingdom
Research Site
Fulham, SW3 6JJ, United Kingdom
Research Site
London, SE1 9RT, United Kingdom
Research Site
Manchester, M20 4BX, United Kingdom
Related Publications (1)
Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, Friedlander M, Arun B, Loman N, Schmutzler RK, Wardley A, Mitchell G, Earl H, Wickens M, Carmichael J. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010 Jul 24;376(9737):235-44. doi: 10.1016/S0140-6736(10)60892-6. Epub 2010 Jul 6.
PMID: 20609467DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
The plasma concentration data was analysed using a population approach and polyadenosine 5' diphosphoribose polymerase (PARP) inhibition data had already been obtained from Study D0810C00002. Hence no pharmacokinetic and PARP inhibition data are included.
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca Clinical Study Information Center
Study Officials
- 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
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 27, 2007
First Posted
June 29, 2007
Study Start
June 15, 2007
Primary Completion
February 27, 2009
Study Completion
December 21, 2022
Last Updated
January 19, 2024
Results First Posted
January 26, 2015
Record last verified: 2024-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.