Dose-finding Study Comparing Efficacy and Safety of a PARP Inhibitor Against Doxil in BRCA+ve Advanced Ovarian Cancer (ICEBERG 3)

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ClinicalTrials.gov Identifier: NCT00628251

Recruitment Status : Active, not recruiting

First Posted : March 5, 2008

Results First Posted : June 3, 2016

Last Update Posted : March 1, 2018

Sponsor:

Information provided by (Responsible Party):

AstraZeneca

Study Description

Brief Summary:

The purpose of the study is to compare the efficacy and safety of 2 doses of drug AZD2281 against liposomal doxorubicin to see which is effective and well tolerated in treating patients with measurable BRCA1- or BRCA2-positive advanced ovarian cancer and who have failed previous platinum therapy.

Condition or disease	Intervention/treatment	Phase
Ovarian Neoplasms	Drug: AZD2281 Drug: Liposomal Doxorubicin	Phase 2

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Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	97 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase II, Open-Label, Randomised, Comparative, International Multicentre Study to Assess the Safety and Efficacy of Different Doses of AZD2281 Given Orally Twice Daily Versus Intravenous Liposomal Doxorubicin Given Monthly in Patients With Advanced BRCA1- or BRCA2-Associated Ovarian Cancer Who Have Failed Previous Platinum-based Chemotherapy
Actual Study Start Date :	July 30, 2008
Actual Primary Completion Date :	September 15, 2009
Estimated Study Completion Date :	December 28, 2018

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Ovarian cancer

MedlinePlus related topics: Ovarian Cancer

Drug Information available for: Doxorubicin Doxorubicin hydrochloride Olaparib

Genetic and Rare Diseases Information Center resources: Ovarian Cancer

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1 AZD2281 Oral 200 mg BID	Drug: AZD2281 200mg oral twice daily
Active Comparator: 2 Liposomal Doxorubicin	Drug: Liposomal Doxorubicin 50mg/m2 Monthly Intravenous Other Name: Doxil®
Experimental: 3 AZD2281 Oral 400 mg BID	Drug: AZD2281 400mg Oral twice daily Other Name: Olaparib

Outcome Measures

Primary Outcome Measures :

Progression Free Survival (PFS) (According to Response Evaluation Criteria in Solid Tumours [RECIST]) [ Time Frame: Tumour assessment was to be assessed at screening, every 8 weeks during the study and at the withdrawal visit, up to 56 weeks. (Data cut-off for primary analysis of PFS: 15 September 2009) ]
PFS was defined as the time to progression from the date of randomisation until the date of radiological assessment of progression per RECIST criteria or death (by any cause in the absence of progression)

Secondary Outcome Measures :

Objective Response Rate (ORR) (According to Response Evaluation Criteria in Solid Tumours - RECIST) [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]
ORR was defined according to RECIST. Complete response (CR) or partial response - (PR)- 30% decrease Patients with a best RECIST response of CR or PR had to have a confirmed response at least 28 days later.
Duration of Response [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]
The duration of response was defined as time (months) from initial assessment of PR/CR until earliest date of objective progression or death. (Values may be underestimated as some patients had not progressed at final analysis so true duration is likely to be greater than that in database.)
Best Percentage Change in Tumour Size [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]
The percentage change (reduction) from baseline in the sum of the lengths of the longest diameter (LD) of the RECIST target lesions were objectively documented, regardless of whether the patient was still taking study medication
Best Percentage Change From Baseline in CA-125 Levels [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]
Best percentage change in cancer antigen 125 (CA-125) levels
Confirmed RECIST Response and/or CA-125 Response [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]
The percentage of patients reporting a RECIST confirmed response and/or a CA-125 response (in the absence of progression). A CA-125 response was defined as a confirmed greater or equal to 50% reduction in CA-125.
Disease Control Rate [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]
The number of patients with confirmed CR (disappearance of all target lesions) or PR (30% decrease in the sum of the longest diameter of target lesions ) or SD ( small changes ) >4 months, divided by the number of randomised patients
Overall Survival (OS) [ Time Frame: At the time of the cut-off for the final analysis of overall survival (30 April 2010) ]
OS was defined as time from randomisation to date of death from any cause. Patients who had not died at time of analysis were censored at last date they were known to be alive. Median OS was not calculable for olaparib groups due to an insufficient number of deaths so the percentage of participants who died are shown along with 95% confidence intervals
Best Quality of Life (QoL) Response for Trial Outcome Index (TOI) [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]
Best HRQoL response using the TOI endpoint. Improvement was defined as a change from baseline of greater than or equal to +7. The TOI score ranges from 0-100.
Best QoL Response for Total Functional Analysis of Cancer Therapy - Ovarian (FACT-O) [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]
Best HRQoL response using the total FACT-O endpoint. Improvement was defined as a change from baseline of greater than or equal to +9.
Best QoL Response for FACT-O Symptom Index (FOSI) [ Time Frame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009) ]
Best HRQoL response using the FOSI endpoint. Improvement was defined as a change from baseline of greater than or equal to +3.

Eligibility Criteria

Information from the National Library of Medicine

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

Criteria

Inclusion Criteria:

Advanced ovarian cancer with positive BRCA1 or BRCA2 status
Progressive or recurrent disease after platinum-based chemotherapy
Measurable disease by RECIST

Exclusion Criteria:

Previous anthracycline treatment
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

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): NCT00628251

Locations


United States, California
Research Site
Los Angeles, California, United States, 90048
Research Site
San Francisco, California, United States, 94115
United States, Florida
Research Site
Boca Raton, Florida, United States, 33428
United States, Massachusetts
Research Site
Boston, Massachusetts, United States, 02115
United States, New York
Research Site
New York, New York, United States, 10065
United States, Texas
Research Site
Houston, Texas, United States, 77030
Australia
Research Site
East Melbourne, Australia, 3002
Research Site
Melbourne, Parkville, Australia, VIC 3050
Research Site
Randwick, Australia, 2031
Belgium
Research Site
Leuven, Belgium, 3000
Germany
Research Site
Köln, Germany, 50924
Research Site
München, Germany, 81377
Israel
Research Site
Haifa, Israel, 31096
Research Site
Tel Aviv, Israel, 6423906
Research Site
Tel-Hashomer, Israel, 52621
Poland
Research Site
Szczecin, Poland, 70-111
Spain
Research Site
Barcelona, Spain, 08035
Research Site
Hospitalet deLlobregat, Spain, 08907
Sweden
Research Site
Lund, Sweden, 22185
United Kingdom
Research Site
Cambridge, United Kingdom, CB2 0QQ
Research Site
Edinburgh, United Kingdom, EH4 2XR
Research Site
London, United Kingdom, SE1 9RT
Research Site
Manchester, United Kingdom, M20 4BX
Research Site
Sutton, United Kingdom, SM2 5PT

Sponsors and Collaborators

AstraZeneca

Investigators


Study Director:	Jane Robertson, BSc, MBCHB, MD	AstraZeneca
Principal Investigator:	Stan Kaye, BSc, MB, FRCP, FRCR, SMedSCi	Royal Marsden NHS Foundation Trust

More Information

Additional Information:

CSR_Synopsis_D0810C00012.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):1013-9. 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.

Yap TA, Carden CP, Kaye SB. Beyond chemotherapy: targeted therapies in ovarian cancer. Nat Rev Cancer. 2009 Mar;9(3):167-81. doi: 10.1038/nrc2583. Review.


Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT00628251 History of Changes
Other Study ID Numbers:	D0810C00012
First Posted:	March 5, 2008 Key Record Dates
Results First Posted:	June 3, 2016
Last Update Posted:	March 1, 2018
Last Verified:	February 2018

Keywords provided by AstraZeneca:


Advanced ovarian cancer BRCA1 protein BRCA2 protein Poly(ADP ribose) polymerases

Additional relevant MeSH terms:


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

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