Ovarian NeoplasmPhase 2ICEBERG 2NCT00494442
Study to Assess the Efficacy and Safety of a PARP Inhibitor for the Treatment of BRCA-positive Advanced Ovarian Cancer
A Phase 2 study testing KU-0059436 (AZD2281)(PARP inhibitor) in people with Ovarian Neoplasm, run by AstraZeneca at 11 sites in 5 countries.
Trial summary
The purpose of the study is to see if the drug KU 0059436 is effective and well tolerated in treating patients with measurable BRCA1- or BRCA2-positive advanced ovarian 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
- Ovarian Neoplasm
- What is being tested?
- KU-0059436 (AZD2281)(PARP inhibitor)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 11 sitesin 5 countries
- Study dates
- 11 Jun 2007to 20 Jul 2017
- 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 ovarian 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
11 sites in 5 countries.
11 sites in 5 countries
United States5 sites
Research Site
Boston, Massachusetts, 02115
Research Site
Houston, Texas, 77030
Research Site
Los Angeles, California, 90048
Research Site
New York, New York, 10065
Research Site
San Francisco, California, 94115
Australia3 sites
Research Site
Melbourne, 3000
Research Site
Melbourne, Parkville, VIC 3050
Research Site
Randwick, 2031
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 Ovarian Cancer
The purpose of the study is to see if the drug KU 0059436 is effective and well tolerated in treating patients with measurable BRCA1- or BRCA2-positive advanced ovarian cancer and for whom no curative therapeutic option exists.
- Conditions
- Ovarian Neoplasm
- Being tested
- KU-0059436 (AZD2281)(PARP inhibitor)
- Keywords
- Advanced ovarian cancer, Poly(ADP ribose) polymerases, KU-0059436, AZD2281, BRCA1 protein, BRCA2 protein
- Medical subject headings
- Ovarian 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.
KU-0059436 (AZD2281)(PARP inhibitor)Drug
Also called Olaparib
oral
KU-0059436 (AZD2281)(PARP inhibitor)Drug
oral
| Study group | Role | What they receive |
|---|---|---|
| KU-0059436 (AZD2281) 100 mg BID | Experimental | Not described Receives: Drug: KU-0059436 (AZD2281)(PARP inhibitor) |
| KU-0059436 (AZD2281) 400 mg BID | Experimental | Not described Receives: Drug: KU-0059436 (AZD2281)(PARP inhibitor) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Confirmed Objective Tumour Response (According to Response Evaluation Criteria In Solid Tumors (RECIST)
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.
Measured: Baseline, every 8 also at study termination or initiation of confounding anti-cancer therapy.
Secondary outcomes (4)
Clinical Benefit (CB)
Clinical Benefit (CB) is defined as the percentage of patients with a RECIST tumour response of confirmed complete response, partial response or stable disease for ≥8 weeks)
Measured: End of study
Duration of Response
Duration of response to olaparib
Measured: End of study
Best Percentage Change in Tumour Size
The best % change (reduction) from baseline in tumour size (defined as the sum of the longest diameters as measured among all target lesions).
Measured: End of study
Progression-Free Survival (PFS)
Progression-Free Survival (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.
Measured: End of study
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 start11 Jun 2007
- Primary completion17 Mar 2009
- Study completion20 Jul 2017
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 (3)Papers the sponsor has linked to this study.
- Other trials for Ovarian NeoplasmStudies 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
- 58 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
- NCT00494442
- Sponsor's protocol ID
- KU36-58
- Other IDs
- D0810C00009
- Acronym
- ICEBERG 2
- Status last verified
- Jun 2018
- First submitted
- 27 Jun 2007
- Last updated
- 1 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Expanded access
- Available
Publications
Matulonis UA, Penson RT, Domchek SM, Kaufman B, Shapira-Frommer R, Audeh MW, Kaye S, Molife LR, Gelmon KA, Robertson JD, Mann H, Ho TW, Coleman RL. Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Ann Oncol. 2016 Jun;27(6):1013-1019. doi: 10.1093/annonc/mdw133. Epub 2016 Mar 8.
PubMed 26961146Ang JE, Gourley C, Powell CB, High H, Shapira-Frommer R, Castonguay V, De Greve J, Atkinson T, Yap TA, Sandhu S, Banerjee S, Chen LM, Friedlander ML, Kaufman B, Oza AM, Matulonis U, Barber LJ, Kozarewa I, Fenwick K, Assiotis I, Campbell J, Chen L, de Bono JS, Gore ME, Lord CJ, Ashworth A, Kaye SB. Efficacy of chemotherapy in BRCA1/2 mutation carrier ovarian cancer in the setting of PARP inhibitor resistance: a multi-institutional study. Clin Cancer Res. 2013 Oct 1;19(19):5485-93. doi: 10.1158/1078-0432.CCR-13-1262. Epub 2013 Aug 6.
PubMed 23922302Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, Scott C, Weitzel JN, Oaknin A, Loman N, Lu K, Schmutzler RK, Matulonis U, Wickens M, Tutt A. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet. 2010 Jul 24;376(9737):245-51. doi: 10.1016/S0140-6736(10)60893-8. Epub 2010 Jul 6.
PubMed 20609468
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2018. 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 Ovarian Cancer
- ClinicalTrials.gov ID
- NCT00494442
- Acronym / sponsor ID
- ICEBERG 2 / KU36-58
- Conditions
- Ovarian Neoplasm
- Keywords
- Advanced ovarian cancer, Poly(ADP ribose) polymerases, KU-0059436, AZD2281, BRCA1 protein, BRCA2 protein
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- KuDOS Pharmaceuticals Limited
- Study start
- 11 Jun 2007 (actual)
- Primary completion
- 17 Mar 2009 (actual)
- Study completion
- 20 Jul 2017 (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 is effective and well tolerated in treating patients with measurable BRCA1- or BRCA2-positive advanced ovarian cancer and for whom no curative therapeutic option exists.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| KU-0059436 (AZD2281) 100 mg BID | Experimental | Drug: KU-0059436 (AZD2281)(PARP inhibitor) |
| KU-0059436 (AZD2281) 400 mg BID | Experimental | Drug: KU-0059436 (AZD2281)(PARP inhibitor) |
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 ovarian 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 |
|---|---|---|
| KU-0059436 (AZD2281)(PARP inhibitor)Also: Olapariboral | Drug | KU-0059436 (AZD2281) 100 mg BID |
| KU-0059436 (AZD2281)(PARP inhibitor)oral | Drug | KU-0059436 (AZD2281) 400 mg BID |
Primary outcome
Confirmed Objective Tumour Response (According to Response Evaluation Criteria In Solid Tumors (RECIST)
Time frame: Baseline, every 8 also at study termination or initiation of confounding anti-cancer therapy.
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.
4 secondary outcomes
Clinical Benefit (CB)
Time frame: End of study
Duration of Response
Time frame: End of study
Best Percentage Change in Tumour Size
Time frame: End of study
Progression-Free Survival (PFS)
Time frame: End of study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26961146Matulonis UA, Penson RT, Domchek SM, Kaufman B, Shapira-Frommer R, Audeh MW, Kaye S, Molife LR, Gelmon KA, Robertson JD, Mann H, Ho TW, Coleman RL. Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Ann Oncol. 2016 Jun;27(6):1013-1019. doi: 10.1093/annonc/mdw133. Epub 2016 Mar 8.
- Derived from this study: PubMed 23922302Ang JE, Gourley C, Powell CB, High H, Shapira-Frommer R, Castonguay V, De Greve J, Atkinson T, Yap TA, Sandhu S, Banerjee S, Chen LM, Friedlander ML, Kaufman B, Oza AM, Matulonis U, Barber LJ, Kozarewa I, Fenwick K, Assiotis I, Campbell J, Chen L, de Bono JS, Gore ME, Lord CJ, Ashworth A, Kaye SB. Efficacy of chemotherapy in BRCA1/2 mutation carrier ovarian cancer in the setting of PARP inhibitor resistance: a multi-institutional study. Clin Cancer Res. 2013 Oct 1;19(19):5485-93. doi: 10.1158/1078-0432.CCR-13-1262. Epub 2013 Aug 6.
- Derived from this study: PubMed 20609468Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, Scott C, Weitzel JN, Oaknin A, Loman N, Lu K, Schmutzler RK, Matulonis U, Wickens M, Tutt A. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet. 2010 Jul 24;376(9737):245-51. doi: 10.1016/S0140-6736(10)60893-8. Epub 2010 Jul 6.
- CSR\_Synopsis\_D0810C00009(KU36-58).pdfLink provided by the sponsor.
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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
11 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing KU-0059436 (AZD2281)(PARP inhibitor) in people with Ovarian Neoplasm, run by AstraZeneca at 11 sites in 5 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 1 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Australia, Germany, Spain, Sweden. 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 Tumour Response (According to Response Evaluation Criteria In Solid Tumors (RECIST) (time frame: Baseline, every 8 also at study termination or initiation of confounding anti-cancer therapy.). 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 NCT00494442, which also lists 3 linked publications.
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 1 Aug 2018.