Dose-finding Study Comparing Efficacy and Safety of a PARP Inhibitor Against Doxil in BRCA+ve Advanced Ovarian Cancer - Full Text View

Purpose

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	Intervention	Phase
Ovarian Neoplasms	Drug: AZD2281 Drug: Liposomal Doxorubicin	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Ovarian Cancer

Drug Information available for: Doxorubicin Doxorubicin hydrochloride

Genetic and Rare Diseases Information Center resources: Ovarian Cancer

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Efficacy comparison of 400 mg bd and 200 mg bd AZD2281 v 50mg/m2 doxil every 4 weeks in BRCA1 or 2 associated advanced ovarian cancer patients by PFS (primary variable), ORR, duration of response and CA-125 levels [ Time Frame: every 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Comparison of safety and tolerability [ Time Frame: every 4 weeks ] [ Designated as safety issue: Yes ]


Enrollment:	125
Study Start Date:	July 2008
Estimated Study Completion Date:	December 2015
Primary Completion Date:	September 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility


Ages Eligible for Study:	18 Years and older
Genders 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00628251

Locations


United States, California
Research Site
Los Angeles, California, United States
Research Site
San Francisco, California, United States
United States, Florida
Research Site
Boca Raton, Florida, United States
United States, Massachusetts
Research Site
Boston, Massachusetts, United States
United States, New York
Research Site
New York, New York, United States
United States, Texas
Research Site
Houston, Texas, United States
Australia
Research Site
East Melbourne, Australia
Research Site
Melbourne, Parkville, Australia
Research Site
Randwick, Australia
Belgium
Research Site
Leuven, Belgium
Germany
Research Site
Köln, Germany
Research Site
München, Germany
Israel
Research Site
Haifa, Israel
Research Site
Tel Aviv, Israel
Research Site
Tel-Hashomer, Israel
Poland
Research Site
Szczecin, Poland
Spain
Research Site
Barcelona, Spain
Research Site
Hospitalet deLlobregat(Barcelo, Spain
Sweden
Research Site
Lund, Sweden
United Kingdom
Research Site
Cambridge, United Kingdom
Research Site
Edinburgh, United Kingdom
Research Site
London, United Kingdom
Research Site
Manchester, United Kingdom
Research Site
Sutton, United Kingdom

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

No publications provided by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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
Study First Received:	February 26, 2008
Last Updated:	November 5, 2014
Health Authority:	United States: Food and Drug Administration United Kingdom: Medicines and Healthcare Products Regulatory Agency Australia: Department of Health and Ageing Therapeutic Goods Administration Germany: Federal Institute for Drugs and Medical Devices Sweden: Medical Products Agency Spain: Ministry of Health Israel: Ministry of Health Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by AstraZeneca:


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

Additional relevant MeSH terms:


Doxorubicin Liposomal doxorubicin Antibiotics, Antineoplastic Antineoplastic Agents Enzyme Inhibitors	Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Therapeutic Uses Topoisomerase II Inhibitors Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on March 03, 2015

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