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

NCT00516373 | Completed Phase 1 DMC

• 3 other identifiers: KU36-92D0810C000022005-001435-29
• Study Type: interventional
• Target: 98
• Locations: 4 countries
• Sites: 5

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

Conditions

Ovarian Neoplasms; BRCA1 Protein; BRCA2 Protein

Keywords

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

Outcome Measures

Primary Outcomes (1)

• To determine the safety, tolerability, dose-limiting toxicity (DLT), and (MTD) of KU-0059436

  assessed at each visit

Secondary Outcomes (1)

• Objective tumour response

  assessed every 8 weeks

Study Arms (1)

KU-0059436

EXPERIMENTAL

KU-0059436 administered orally twice daily

Drug: KU-0059436 (AZD2281)(PARP inhibitor)

Interventions

KU-0059436 (AZD2281)(PARP inhibitor) DRUG

oral

Also known as: Olaparib

KU-0059436

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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).

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (5)

Research Site

Brussels, 1090, Belgium

Location

Research Site

Amsterdam, 1066 CX, Netherlands

Location

Research Site

Szczecin, 70-115, Poland

Location

Research Site

Edinburgh, EH4 2XR, United Kingdom

Location

Research Site

London, SM2 5NG, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 26961146 DERIVED

• 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.

  PMID: 23922302 DERIVED

• 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.

  PMID: 19553641 DERIVED

Related Links

• CSR\_Synopsis\_D0810C00002(KU36-92).pdf

MeSH Terms

Conditions

Ovarian Neoplasms; Fanconi Anemia, Complementation Group D1

Interventions

olaparib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Jane Robertson, BSc, MBCHB, MD

  AstraZeneca

  STUDY DIRECTOR

• Dr. Johann De Bono, PhD MRCP FRCR

  Royal Marsden Hospital Trust, London, UK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2007
• First Posted: August 15, 2007
• Study Start: July 11, 2005
• Primary Completion: December 17, 2008
• Study Completion: April 26, 2023
• Last Updated: February 22, 2024

Record last verified: 2024-02

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

Locations

NL (1); PL (1); GB (2); BE (1)