Ovarian NeoplasmsPhase 1NCT00516373
A Study to Assess the Safety and Pharmacokinetics of an Inhibitor of Poly ADP-Ribose Polymerase-1 (PARP)
A Phase 1 study testing KU-0059436 (AZD2281)(PARP inhibitor) in people with Ovarian Neoplasms and BRCA1 Protein, run by AstraZeneca at 5 sites in 4 countries.
Trial summary
To determine the safety, tolerability, dose-limiting toxicity (DLT), pharmacokinetic-pharmacodynamic profile, and maximum tolerated dose (MTD) of KU-0059436 when administered orally to patients with advanced solid tumours. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Ovarian Neoplasms, BRCA1 Protein, BRCA2 Protein
- 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
- 98 participants
- Where
- 5 sitesin 4 countries
- Study dates
- 11 Jul 2005to 26 Apr 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed malignant advanced solid tumour refractory to standard therapy or for which no suitable effective standard therapy exists.
Who cannot join
- Anti-cancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within the 4 weeks prior to trial entry (or a longer period depending on the defined characteristics of the agents used).
Trial locations and contacts
5 sites in 4 countries.
5 sites in 4 countries
United Kingdom2 sites
Research Site
Edinburgh, EH4 2XR
Research Site
London, SM2 5NG
About this study
Official title: A Phase I, Pharmacokinetic and Biological Evaluation of a Small Molecule Inhibitor of Poly ADP-Ribose Polymerase-1 (PARP-1), KU-0059436, in Patients With Advanced Tumours.
To determine the safety, tolerability, dose-limiting toxicity (DLT), pharmacokinetic-pharmacodynamic profile, and maximum tolerated dose (MTD) of KU-0059436 when administered orally to patients with advanced solid tumours. To further evaluate the safety and efficacy of KU-0059436 in an expanded cohort of BCRA-enriched population, primarily ovarian cancer patients
- Conditions
- Ovarian Neoplasms, BRCA1 Protein, BRCA2 Protein
- Being tested
- KU-0059436 (AZD2281)(PARP inhibitor)
- Keywords
- advanced ovarian cancer, BRCA 1 protein, BRCA 2 protein, Poly(ADP ribose)polymerases
- 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
| Study group | Role | What they receive |
|---|---|---|
| KU-0059436 | Experimental | KU-0059436 administered orally twice daily Receives: Drug: KU-0059436 (AZD2281)(PARP inhibitor) |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the safety, tolerability, dose-limiting toxicity (DLT), and (MTD) of KU-0059436
Measured: assessed at each visit
Secondary outcomes (1)
Objective tumour response
Measured: assessed every 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2007 (estimated)
- Study start11 Jul 2005
- Primary completion17 Dec 2008
- Study completion26 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Ovarian 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 98 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jane Robertson, BSc, MBCHB, MD, Study director, AstraZenecaDr. Johann De Bono, PhD MRCP FRCR, Principal investigator, Royal Marsden Hospital Trust, London, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00516373
- Sponsor's protocol ID
- KU36-92
- Other IDs
- D0810C00002, 2005-001435-29, 2005
- Status last verified
- Feb 2024
- First submitted
- 13 Aug 2007
- Last updated
- 22 Feb 2024
- Results posted
- No
- 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
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 23922302Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, Mortimer P, Swaisland H, Lau A, O'Connor MJ, Ashworth A, Carmichael J, Kaye SB, Schellens JH, de Bono JS. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009 Jul 9;361(2):123-34. doi: 10.1056/NEJMoa0900212. Epub 2009 Jun 24.
PubMed 19553641
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Pharmacokinetic and Biological Evaluation of a Small Molecule Inhibitor of Poly ADP-Ribose Polymerase-1 (PARP-1), KU-0059436, in Patients With Advanced Tumours.
- ClinicalTrials.gov ID
- NCT00516373
- Acronym / sponsor ID
- KU36-92
- Conditions
- Ovarian Neoplasms, BRCA1 Protein, BRCA2 Protein
- Keywords
- advanced ovarian cancer, BRCA 1 protein, BRCA 2 protein, Poly(ADP ribose)polymerases
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 98 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 11 Jul 2005 (actual)
- Primary completion
- 17 Dec 2008 (actual)
- Study completion
- 26 Apr 2023 (actual)
- First posted
- 15 Aug 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine the safety, tolerability, dose-limiting toxicity (DLT), pharmacokinetic-pharmacodynamic profile, and maximum tolerated dose (MTD) of KU-0059436 when administered orally to patients with advanced solid tumours. To further evaluate the safety and efficacy of KU-0059436 in an expanded cohort of BCRA-enriched population, primarily ovarian cancer patients
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| KU-0059436 | Experimental | Drug: KU-0059436 (AZD2281)(PARP inhibitor)KU-0059436 administered orally twice daily |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Confirmed malignant advanced solid tumour refractory to standard therapy or for which no suitable effective standard therapy exists.
Key exclusion criteria (1 listed)
- Anti-cancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within the 4 weeks prior to trial entry (or a longer period depending on the defined characteristics of the agents used).
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 |
Primary outcome
To determine the safety, tolerability, dose-limiting toxicity (DLT), and (MTD) of KU-0059436
Time frame: assessed at each visit
1 secondary outcome
Objective tumour response
Time frame: assessed every 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2024.
- 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 19553641Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, Mortimer P, Swaisland H, Lau A, O'Connor MJ, Ashworth A, Carmichael J, Kaye SB, Schellens JH, de Bono JS. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009 Jul 9;361(2):123-34. doi: 10.1056/NEJMoa0900212. Epub 2009 Jun 24.
- CSR\_Synopsis\_D0810C00002(KU36-92).pdfLink provided by the sponsor.
- 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.
Jane Robertson, BSc, MBCHB, MD study director
AstraZeneca
Dr. Johann De Bono, PhD MRCP FRCR principal investigator
Royal Marsden Hospital Trust, London, UK
5 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing KU-0059436 (AZD2281)(PARP inhibitor) in people with Ovarian Neoplasms and BRCA1 Protein, run by AstraZeneca at 5 sites in 4 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 1 inclusion and 1 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 22 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United Kingdom, Belgium, Netherlands, Poland. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To determine the safety, tolerability, dose-limiting toxicity (DLT), and (MTD) of KU-0059436 (time frame: assessed at each visit). 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 NCT00516373, 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 22 Feb 2024.