Dose-finding Study Comparing Efficacy and Safety of a PARP Inhibitor Against Doxil in BRCA+ve Advanced Ovarian Cancer (ICEBERG 3)
This study is ongoing, but not recruiting participants.
Sponsor:
AstraZeneca
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00628251
First received: February 26, 2008
Last updated: August 24, 2016
Last verified: August 2016
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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:
Further study details as provided by AstraZeneca:
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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]Best HRQoL response using the FOSI endpoint. Improvement was defined as a change from baseline of greater than or equal to +3.
| Enrollment: | 125 |
| Study Start Date: | July 2008 |
| Estimated Study Completion Date: | December 2016 |
| 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 to 130 Years (Adult, Senior) |
| 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
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, 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
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT00628251 History of Changes |
| Other Study ID Numbers: | D0810C00012 |
| Study First Received: | February 26, 2008 |
| Results First Received: | January 14, 2015 |
| Last Updated: | August 24, 2016 |
| 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:
|
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 |
ClinicalTrials.gov processed this record on September 23, 2016