Clinical trial NCT00494234: Study to Assess The Efficacy and Safety of a PARP Inhibitor For The Treatment of BRCA-positive Advanced Breast Cancer
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 Breast Cancer.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Neoplasms
Keywords: Advanced breast cancer
Poly(ADP ribose) polymerases
AZD2281,KU-0059436 (olaparib)
BRCA1 protein
BRCA2 protein
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: KuDOS Pharmaceuticals Limited
First posted: 2007-06-29
Enrollment: 54
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to see if the drug KU-0059436 (olaparib) is effective and well tolerated in treating participants with measurable breast cancer gene (BRCA)1- or BRCA2-positive advanced breast cancer and for whom no curative therapeutic option exists.

Detailed description: This is a Phase II, open-label, non-comparative, international, multicenter study to assess the efficacy and safety of olaparib when given orally twice daily (bd) in participants with advanced BRCA1- or BRCA2- associated breast cancer. Two sequential participant cohorts will receive continuous oral olaparib in 28-day cycles. The first cohort will receive 400 mg bd and the second cohort will receive 100 mg bd.

Eligibility criteria: Inclusion Criteria:

* Advanced breast cancer with positive BRCA1 or BRCA2 status
* Failed at least one prior chemotherapy
* In investigators opinion, no curative standard therapy exists
* Measurable disease

Exclusion Criteria:

* 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

Primary outcomes:
measure: Confirmed Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
timeFrame: Baseline (Days -28 to 0), Day 1 of Cycle 3, thereafter every alternate cycles until study termination or withdrawal (approximately up to 2 years)
Secondary outcomes:
measure: Duration of Response (DoR) to Olaparib
timeFrame: Baseline (Days -28 to 0), Day 1 of Cycle 3, thereafter every alternate cycles until study termination or withdrawal (approximately up to 2 years)
measure: Clinical Benefit Rate (CBR)
timeFrame: From Day 1 of Cycle 3 through study withdrawal (approximately up to 2 years)
measure: Best Percentage Change in Tumor Size
timeFrame: Baseline (Days -28 to 0) through study withdrawal (approximately up to 2 years)
measure: Progression-free Survival (PFS)
timeFrame: Baseline (Days -28 to 0), Day 1 of Cycle 3, thereafter every alternate cycles until study termination or withdrawal (approximately up to 2 years)
measure: Number of Participants With Improvement in Eastern Co-operative Oncology Group (ECOG) Performance Status Total Score From Baseline
timeFrame: Screening (Days -7 to 0), Day 1 Cycle 7 (ie, after completing 6 cycles of treatment) and study withdrawal (approximately up to 2 years).
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: Day 1 through Day 480 (maximum observed duration)
measure: Number of Participants With Clinically Significant Changes in Vital Signs From Baseline
timeFrame: Day 1 through Day 480 (maximum observed duration)
measure: Number of Participants With at Least 2-Grade Change From Baseline to Worst Toxicity Grade in Clinical Laboratory Parameters
timeFrame: Day 1 through Day 480 (maximum observed duration)
Other outcomes:
Locations:
city: West Hollywood
country: United States
facility: Research Site
state: California
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Melbourne
country: Australia
facility: Research Site
city: Randwick
country: Australia
facility: Research Site
city: Duarte
country: Canada
facility: Research Site
state: CA
city: Kiel
country: Germany
facility: Research Site
city: Köln
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Tel-Aviv
country: Israel
facility: Research Site
city: Hospitalet deLlobregat
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Edinburgh
country: United Kingdom
facility: Research Site
city: Fulham
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
affiliation: KuDOS Pharmaceuticals Limited
name: James Carmichael, BSc, MBChB, MD, FRCP
role: STUDY_DIRECTOR
affiliation: Guy's and St Thomas's NHS Foundation Trust, London, UK
name: Andrew Tutt, PhD MRCP FRCR
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, Friedlander M, Arun B, Loman N, Schmutzler RK, Wardley A, Mitchell G, Earl H, Wickens M, Carmichael J. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010 Jul 24;376(9737):235-44. doi: 10.1016/S0140-6736(10)60892-6. Epub 2010 Jul 6.