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Study to Assess the Efficacy and Safety of a PARP Inhibitor for the Treatment of BRCA-positive Advanced Ovarian Cancer (ICEBERG 2)

Primary Purpose

Ovarian Neoplasm

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
KU-0059436 (AZD2281)(PARP inhibitor)
KU-0059436 (AZD2281)(PARP inhibitor)
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Neoplasm focused on measuring Advanced ovarian cancer, Poly(ADP ribose) polymerases, KU-0059436, AZD2281, BRCA1 protein, BRCA2 protein

Eligibility Criteria

18 Years - 130 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

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

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

KU-0059436 (AZD2281) 100 mg BID

KU-0059436 (AZD2281) 400 mg BID

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Clinical Benefit (CB)
Clinical Benefit (CB) is defined as the percentage of patients with a RECIST tumour response of confirmed complete response, partial response or stable disease for ≥8 weeks)
Duration of Response
Duration of response to olaparib
Best Percentage Change in Tumour Size
The best % change (reduction) from baseline in tumour size (defined as the sum of the longest diameters as measured among all target lesions).
Progression-Free Survival (PFS)
Progression-Free Survival (PFS) is defined as the time from first dose to the earlier date of radiologic progression (as per RECIST criteria) or death by any cause in the absence of objective progression.

Full Information

First Posted
June 27, 2007
Last Updated
July 4, 2018
Sponsor
AstraZeneca
Collaborators
KuDOS Pharmaceuticals Limited
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1. Study Identification

Unique Protocol Identification Number
NCT00494442
Brief Title
Study to Assess the Efficacy and Safety of a PARP Inhibitor for the Treatment of BRCA-positive Advanced Ovarian Cancer
Acronym
ICEBERG 2
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 Ovarian Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
June 11, 2007 (Actual)
Primary Completion Date
March 17, 2009 (Actual)
Study Completion Date
July 20, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
Collaborators
KuDOS Pharmaceuticals Limited

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Neoplasm
Keywords
Advanced ovarian cancer, Poly(ADP ribose) polymerases, KU-0059436, AZD2281, BRCA1 protein, BRCA2 protein

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
58 (Actual)

8. Arms, Groups, and Interventions

Arm Title
KU-0059436 (AZD2281) 100 mg BID
Arm Type
Experimental
Arm Title
KU-0059436 (AZD2281) 400 mg BID
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
KU-0059436 (AZD2281)(PARP inhibitor)
Other Intervention Name(s)
Olaparib
Intervention Description
oral
Intervention Type
Drug
Intervention Name(s)
KU-0059436 (AZD2281)(PARP inhibitor)
Intervention Description
oral
Primary Outcome Measure Information:
Title
Confirmed Objective Tumour Response (According to Response Evaluation Criteria In Solid Tumors (RECIST)
Description
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.
Time Frame
Baseline, every 8 also at study termination or initiation of confounding anti-cancer therapy.
Secondary Outcome Measure Information:
Title
Clinical Benefit (CB)
Description
Clinical Benefit (CB) is defined as the percentage of patients with a RECIST tumour response of confirmed complete response, partial response or stable disease for ≥8 weeks)
Time Frame
End of study
Title
Duration of Response
Description
Duration of response to olaparib
Time Frame
End of study
Title
Best Percentage Change in Tumour Size
Description
The best % change (reduction) from baseline in tumour size (defined as the sum of the longest diameters as measured among all target lesions).
Time Frame
End of study
Title
Progression-Free Survival (PFS)
Description
Progression-Free Survival (PFS) is defined as the time from first dose to the earlier date of radiologic progression (as per RECIST criteria) or death by any cause in the absence of objective progression.
Time Frame
End of study

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
130 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James Carmichael, BSc MBChB MD FRCP
Organizational Affiliation
KuDOS Pharmaceuticals Limited
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Andrew Tutt, PhD MRCP FRCR
Organizational Affiliation
Guy's and St Thomas's NHS Foundation Trust, London, UK
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Research Site
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Research Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Research Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Research Site
City
Melbourne, Parkville
ZIP/Postal Code
VIC 3050
Country
Australia
Facility Name
Research Site
City
Melbourne
ZIP/Postal Code
3000
Country
Australia
Facility Name
Research Site
City
Randwick
ZIP/Postal Code
2031
Country
Australia
Facility Name
Research Site
City
Köln
ZIP/Postal Code
50931
Country
Germany
Facility Name
Research Site
City
Hospitalet deLlobregat
ZIP/Postal Code
08907
Country
Spain
Facility Name
Research Site
City
Lund
ZIP/Postal Code
S-221 85
Country
Sweden

12. IPD Sharing Statement

Citations:
PubMed Identifier
26961146
Citation
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.
Results Reference
derived
PubMed Identifier
23922302
Citation
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.
Results Reference
derived
PubMed Identifier
20609468
Citation
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.
Results Reference
derived
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=734&filename=CSR_Synopsis_D0810C00009(KU36-58).pdf
Description
CSR_Synopsis_D0810C00009(KU36-58).pdf

Learn more about this trial

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

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