A Study to Assess the Safety and Pharmacokinetics of an Inhibitor of Poly ADP-Ribose Polymerase-1 (PARP)

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ClinicalTrials.gov Identifier: NCT00516373

Recruitment Status : Active, not recruiting

First Posted : August 15, 2007

Last Update Posted : September 14, 2020

Sponsor:

Information provided by (Responsible Party):

AstraZeneca

Study Description

Brief 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. To further evaluate the safety and efficacy of KU-0059436 in an expanded cohort of BCRA-enriched population, primarily ovarian cancer patients.

Condition or disease	Intervention/treatment	Phase
Ovarian Neoplasms BRCA1 Protein BRCA2 Protein	Drug: KU-0059436 (AZD2281)(PARP inhibitor)	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	98 participants
Allocation:	N/A
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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.
Actual Study Start Date :	July 4, 2005
Actual Primary Completion Date :	December 17, 2008
Estimated Study Completion Date :	December 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Ovarian cancer

Drug Information available for: Olaparib

Genetic and Rare Diseases Information Center resources: Ovarian Cancer Ovarian Epithelial Cancer

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: KU-0059436 KU-0059436 administered orally twice daily	Drug: KU-0059436 (AZD2281)(PARP inhibitor) oral Other Name: Olaparib

Outcome Measures

Primary Outcome Measures :

To determine the safety, tolerability, dose-limiting toxicity (DLT), and (MTD) of KU-0059436 [ Time Frame: assessed at each visit ]

Secondary Outcome Measures :

Objective tumour response [ Time Frame: assessed every 8 weeks ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 130 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Confirmed malignant advanced solid tumour refractory to standard therapy or for which no suitable effective standard therapy exists.

Exclusion Criteria:

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).

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00516373

Locations

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Belgium
Research Site
Brussels, Belgium
Netherlands
Research Site
Amsterdam, Netherlands
Poland
Research Site
Szczecin, Poland
United Kingdom
Research Site
Edinburgh, United Kingdom
Research Site
London, United Kingdom

Sponsors and Collaborators

AstraZeneca

Investigators

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Study Director:	Jane Robertson, BSc, MBCHB, MD	AstraZeneca
Principal Investigator:	Dr. Johann De Bono, PhD MRCP FRCR	Royal Marsden Hospital Trust, London, UK

More Information

Additional Information:

CSR_Synopsis_D0810C00002(KU36-92).pdf This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Ang 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.

Fong 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.

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Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT00516373
Other Study ID Numbers:	KU36-92 D0810C00002
First Posted:	August 15, 2007 Key Record Dates
Last Update Posted:	September 14, 2020
Last Verified:	September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	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
Supporting Materials:	Study Protocol Statistical Analysis Plan (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
URL:	https://astrazenecagroup-dt.pharmacm.com/DT/Home

Keywords provided by AstraZeneca:


advanced ovarian cancer BRCA 1 protein BRCA 2 protein Poly(ADP ribose)polymerases

Additional relevant MeSH terms:

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Ovarian Neoplasms Endocrine Gland Neoplasms Neoplasms by Site Neoplasms Ovarian Diseases Adnexal Diseases Genital Neoplasms, Female Urogenital Neoplasms	Endocrine System Diseases Gonadal Disorders Olaparib Poly(ADP-ribose) Polymerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents

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