Study to Assess the Efficacy and Safety of a PARP Inhibitor for the Treatment of BRCA-positive Advanced Ovarian Cancer

NCT00494442 | Completed Phase 2 Results DMC

• 2 other identifiers: KU36-58D0810C00009
• Study Type: interventional
• Target: 58
• Locations: 5 countries
• Sites: 11

Brief 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.

Conditions

Ovarian Neoplasm

Keywords

Advanced ovarian cancer; Poly(ADP ribose) polymerases; KU-0059436; AZD2281; BRCA1 protein; BRCA2 protein

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, every 8 also at study termination or initiation of confounding anti-cancer therapy.

Secondary Outcomes (4)

• Clinical Benefit (CB)

  End of study

• Duration of Response

  End of study

• Best Percentage Change in Tumour Size

  End of study

• Progression-Free Survival (PFS)

  End of study

Study Arms (2)

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)

Interventions

KU-0059436 (AZD2281)(PARP inhibitor) DRUG

oral

Also known as: Olaparib

KU-0059436 (AZD2281) 100 mg BID

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead
• KuDOS Pharmaceuticals Limited: collaborator

Study Sites (11)

Research Site

Los Angeles, California, 90048, United States

Location

Research Site

San Francisco, California, 94115, United States

Location

Research Site

Boston, Massachusetts, 02115, United States

Location

Research Site

New York, New York, 10065, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Research Site

Melbourne, 3000, Australia

Location

Research Site

Melbourne, Parkville, VIC 3050, Australia

Location

Research Site

Randwick, 2031, Australia

Location

Research Site

Cologne, 50931, Germany

Location

Research Site

Hospitalet deLlobregat, 08907, Spain

Location

Research Site

Lund, S-221 85, Sweden

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

• Audeh 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.

  PMID: 20609468 DERIVED

Related Links

• CSR\_Synopsis\_D0810C00009(KU36-58).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

Results Point of Contact

• Title: Gerard Lynch
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• James Carmichael, BSc MBChB MD FRCP

  KuDOS Pharmaceuticals Limited

  STUDY DIRECTOR

• Andrew Tutt, PhD MRCP FRCR

  Guy's and St Thomas's NHS Foundation Trust, London, UK

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: June 27, 2007
• First Posted: June 29, 2007
• Study Start: June 11, 2007
• Primary Completion: March 17, 2009
• Study Completion: July 20, 2017
• Last Updated: August 1, 2018
• Results First Posted: January 26, 2015

Record last verified: 2018-06

Locations

ES (1); AU (3); SE (1); US (5); DE (1)