Breast NeoplasmsPhase 2ICEBERG 1NCT00494234
Study to Assess The Efficacy and Safety of a PARP Inhibitor For The Treatment of BRCA-positive Advanced Breast Cancer
A Phase 2 study testing Olaparib in people with Breast Neoplasms, run by AstraZeneca at 17 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 130 years, women only
- Conditions the study is for
- Breast Neoplasms
- What is being tested?
- Olaparib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 17 sitesin 8 countries
- Study dates
- 15 Jun 2007to 21 Dec 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
17 sites in 8 countries.
17 sites in 8 countries
United Kingdom5 sites
Research Site
Cambridge, CB2 0QQ
Research Site
Edinburgh, EH4 2XR
Research Site
Fulham, SW3 6JJ
Research Site
London, SE1 9RT
Research Site
Manchester, M20 4BX
Germany3 sites
Research Site
Cologne, 50937
Research Site
Kiel, 24105
Research Site
München, 81675
United States2 sites
Research Site
Boston, Massachusetts, 02115
Research Site
West Hollywood, California, 90048
Spain2 sites
Research Site
Hospitalet deLlobregat, 08907
Research Site
Madrid, 08035
About this study
Official title: 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.
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.
Read the detailed description
This is a Phase II, open-label, non-comparative, international, multicenter study to assess the efficacy and safety of olaparib when given orally twice daily (bd) in participants with advanced BRCA1- or BRCA2- associated breast cancer. Two sequential participant cohorts will receive continuous oral olaparib in 28-day cycles. The first cohort will receive 400 mg bd and the second cohort will receive 100 mg bd.
- Conditions
- Breast Neoplasms
- Being tested
- Olaparib
- Keywords
- Advanced breast cancer, Poly(ADP ribose) polymerases, AZD2281,KU-0059436 (olaparib), BRCA1 protein, BRCA2 protein
- Medical subject headings
- Breast Neoplasms, Fanconi Anemia, Complementation Group D1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlaparibDrug
Also called AZD2281, KU-0059436
Participants will receive capsules of olaparib orally as stated in arm description.
| Study group | Role | What they receive |
|---|---|---|
| Olaparib 100 mg | Experimental | Participants 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. Receives: Drug: Olaparib |
| Olaparib 400 mg | Experimental | Participants 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. Receives: Drug: Olaparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Duration of response is defined as the date of progression per RECIST criteria - the date when CR or PR [whichever is earliest] is confirmed + 1. The CR is defined as disappearance of all TLs. The PR is defined as at least a 30% decrease in the sum of LD taking as reference the baseline sum of LD. Duration of response was analyzed for those participants who had OR.
Measured: 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)
The CBR is defined as the percentage of participants with a RECIST tumor response of confirmed CR, PR or stable disease (SD) for ≥ 8 weeks +/- 1 week visit window. The CR is defined as disappearance of all TLs. The PR is defined as at least a 30% decrease in the sum of LD taking as reference the baseline sum of LD. Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum of LD since the treatment started.
Measured: From Day 1 of Cycle 3 through study withdrawal (approximately up to 2 years)
Best Percentage Change in Tumor Size
The tumor size is defined as the sum of the longest diameters as measured among all target lesions. At each assessment, the percentage change in tumor size is defined as 100 × 1 - (sum of all target lesion diameters at visit/sum of all target lesion diameters at baseline).
Measured: Baseline (Days -28 to 0) through study withdrawal (approximately up to 2 years)
Progression-free Survival (PFS)
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 participants who were withdrawn from the study without disease progression were regarded as censored at their last evaluable RECIST assessment. Where participants had not progressed at the termination of the study, they were also regarded as censored at their last evaluable RECIST assessment. PFS was analyzed using Kaplan-Meier estimate.
Measured: 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
ECOG performance status is used by researchers to assess how a participant's disease is progressing. The scores are: 0=Fully Active, able to carry out work without restrictions; 1=Restricted activity and able to carry out light work or sedentary nature; 2=capable of self-care but unable to carry out work activities; 3=Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=Completely Disabled, and totally confined to bed or chair; 5=Dead. Change in ECOG performance status was defined as improved (less than the baseline value), no change (same as at baseline), worsened (greater than the baseline value) or missing (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.
Measured: Screening (Days -7 to 0), Day 1 Cycle 7 (ie, after completing 6 cycles of treatment) and study withdrawal (approximately up to 2 years).
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Measured: Day 1 through Day 480 (maximum observed duration)
Number of Participants With Clinically Significant Changes in Vital Signs From Baseline
Number of participants with clinically significant changes in vital signs are reported. Vital sign parameters included body temperature, blood pressure, and pulse rate.
Measured: Day 1 through Day 480 (maximum observed duration)
Number of Participants With at Least 2-Grade Change From Baseline to Worst Toxicity Grade in Clinical Laboratory Parameters
Number of participants with at least 2-grade change from baseline to worst toxicity grade in clinical laboratory parameters are reported. Laboratory parameters included hematology, clinical chemistry, and urinalysis.
Measured: Day 1 through Day 480 (maximum observed duration)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2007 (estimated)
- Study start15 Jun 2007
- Primary completion27 Feb 2009
- Study completion21 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- KuDOS Pharmaceuticals Limited
- Responsible party
- Sponsor
- Investigators
- James Carmichael, BSc, MBChB, MD, FRCP, Study director, KuDOS Pharmaceuticals LimitedAndrew Tutt, PhD MRCP FRCR, Principal investigator, Guy's and St Thomas's NHS Foundation Trust, London, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00494234
- Sponsor's protocol ID
- KU36-44
- Other IDs
- D0810C00008, 2006-006458-91
- Acronym
- ICEBERG 1
- Status last verified
- Jan 2024
- First submitted
- 27 Jun 2007
- Last updated
- 19 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 20609467
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT00494234
- Acronym / sponsor ID
- ICEBERG 1 / KU36-44
- Conditions
- Breast Neoplasms
- Keywords
- Advanced breast cancer, Poly(ADP ribose) polymerases, AZD2281,KU-0059436 (olaparib), BRCA1 protein, BRCA2 protein
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- KuDOS Pharmaceuticals Limited
- Study start
- 15 Jun 2007 (actual)
- Primary completion
- 27 Feb 2009 (actual)
- Study completion
- 21 Dec 2022 (actual)
- First posted
- 29 Jun 2007 (estimated)
- Results
- Posted 26 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a Phase II, open-label, non-comparative, international, multicenter study to assess the efficacy and safety of olaparib when given orally twice daily (bd) in participants with advanced BRCA1- or BRCA2- associated breast cancer. Two sequential participant cohorts will receive continuous oral olaparib in 28-day cycles. The first cohort will receive 400 mg bd and the second cohort will receive 100 mg bd.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Olaparib 100 mg | Experimental | Drug: OlaparibParticipants 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 | Experimental | Drug: OlaparibParticipants 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. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OlaparibAlso: AZD2281, KU-0059436Participants will receive capsules of olaparib orally as stated in arm description. | Drug | Olaparib 100 mg, Olaparib 400 mg |
Primary outcome
Confirmed Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
Time frame: Baseline (Days -28 to 0), Day 1 of Cycle 3, thereafter every alternate cycles until study termination or withdrawal (approximately up to 2 years)
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.
8 secondary outcomes
Duration of Response (DoR) to Olaparib
Time frame: 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)
Time frame: From Day 1 of Cycle 3 through study withdrawal (approximately up to 2 years)
Best Percentage Change in Tumor Size
Time frame: Baseline (Days -28 to 0) through study withdrawal (approximately up to 2 years)
Progression-free Survival (PFS)
Time frame: 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
Time frame: Screening (Days -7 to 0), Day 1 Cycle 7 (ie, after completing 6 cycles of treatment) and study withdrawal (approximately up to 2 years).
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Time frame: Day 1 through Day 480 (maximum observed duration)
Number of Participants With Clinically Significant Changes in Vital Signs From Baseline
Time frame: Day 1 through Day 480 (maximum observed duration)
Number of Participants With at Least 2-Grade Change From Baseline to Worst Toxicity Grade in Clinical Laboratory Parameters
Time frame: Day 1 through Day 480 (maximum observed duration)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 20609467Tutt 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Carmichael, BSc, MBChB, MD, FRCP study director
KuDOS Pharmaceuticals Limited
Andrew Tutt, PhD MRCP FRCR principal investigator
Guy's and St Thomas's NHS Foundation Trust, London, UK
17 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Olaparib in people with Breast Neoplasms, run by AstraZeneca at 17 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United Kingdom, Germany, United States, Australia, Spain and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Confirmed Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria (time frame: Baseline (Days -28 to 0), Day 1 of Cycle 3, thereafter every alternate cycles until study termination or withdrawal (approximately up to 2 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00494234, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2024.