Dose-finding Study Comparing Efficacy and Safety of a PARP Inhibitor Against Doxil in BRCA+ve Advanced Ovarian Cancer - Clinical Trial for Ovarian Neoplasms | NCT00628251

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

AZD2281

Liposomal Doxorubicin

AZD2281

About this trial

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

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
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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

1

2

3

Arm Description

AZD2281 Oral 200 mg BID

Liposomal Doxorubicin

AZD2281 Oral 400 mg BID

Outcomes

Primary Outcome Measures

Progression Free Survival (PFS)

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)

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.

Disease Control Rate

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 Duration of Response

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

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

Best percentage change in cancer antigen 125 (CA-125) levels

Confirmed RECIST Response and/or CA-125 Response

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.

Overall Survival (OS)

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)

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)

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)

Best HRQoL response using the FOSI endpoint. Improvement was defined as a change from baseline of greater than or equal to +3.

Full Information

NCT ID

NCT00628251

First Posted

February 26, 2008

Last Updated

November 12, 2019

Sponsor

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT00628251

Brief Title

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

Acronym

ICEBERG 3

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2019

Overall Recruitment Status

Completed

Study Start Date

July 30, 2008 (Actual)

Primary Completion Date

September 15, 2009 (Actual)

Study Completion Date

September 19, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

4. Oversight

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ovarian Neoplasms

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

97 (Actual)

8. Arms, Groups, and Interventions

Arm Title

1

Arm Type

Experimental

Arm Description

AZD2281 Oral 200 mg BID

Arm Title

2

Arm Type

Active Comparator

Arm Description

Liposomal Doxorubicin

Arm Title

3

Arm Type

Experimental

Arm Description

AZD2281 Oral 400 mg BID

Intervention Type

Drug

Intervention Name(s)

AZD2281

Other Intervention Name(s)

Olaparib

Intervention Description

400mg Oral twice daily

Intervention Type

Drug

Intervention Name(s)

Liposomal Doxorubicin

Other Intervention Name(s)

Doxil®

Intervention Description

50mg/m2 Monthly Intravenous

Intervention Type

Drug

Intervention Name(s)

AZD2281

Intervention Description

200mg oral twice daily

Primary Outcome Measure Information:

Title

Progression Free Survival (PFS)

Description

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)

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)

Secondary Outcome Measure Information:

Title

Objective Response Rate (ORR)

Description

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.

Time Frame

At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)

Title

Disease Control Rate

Description

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

Time Frame

At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)

Title

Overall Duration of Response

Description

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.)

Time Frame

At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)

Title

Best Percentage Change in Tumour Size

Description

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

Time Frame

At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)

Title

Best Percentage Change From Baseline in CA-125 Levels

Description

Best percentage change in cancer antigen 125 (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)

Title

Confirmed RECIST Response and/or CA-125 Response

Description

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.

Time Frame

At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)

Title

Overall Survival (OS)

Description

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

Time Frame

At the time of the cut-off for the final analysis of overall survival (30 April 2010)

Title

Best Quality of Life (QoL) Response for Trial Outcome Index (TOI)

Description

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.

Time Frame

At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)

Title

Best QoL Response for Total Functional Analysis of Cancer Therapy - Ovarian (FACT-O)

Description

Best HRQoL response using the total FACT-O endpoint. Improvement was defined as a change from baseline of greater than or equal to +9.

Time Frame

At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)

Title

Best QoL Response for FACT-O Symptom Index (FOSI)

Description

Best HRQoL response using the FOSI endpoint. Improvement was defined as a change from baseline of greater than or equal to +3.

Time Frame

At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)

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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jane Robertson, BSc, MBCHB, MD

Organizational Affiliation

AstraZeneca

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Stan Kaye, BSc, MB, FRCP, FRCR, SMedSCi

Organizational Affiliation

Royal Marsden NHS Foundation Trust

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

Boca Raton

State/Province

Florida

ZIP/Postal Code

33428

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

East Melbourne

ZIP/Postal Code

3002

Country

Australia

Facility Name

Research Site

City

Melbourne, Parkville

ZIP/Postal Code

VIC 3050

Country

Australia

Facility Name

Research Site

City

Randwick

ZIP/Postal Code

2031

Country

Australia

Facility Name

Research Site

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

Facility Name

Research Site

City

Köln

ZIP/Postal Code

50937

Country

Germany

Facility Name

Research Site

City

München

ZIP/Postal Code

81377

Country

Germany

Facility Name

Research Site

City

Haifa

ZIP/Postal Code

31096

Country

Israel

Facility Name

Research Site

City

Ramat Gan

ZIP/Postal Code

52621

Country

Israel

Facility Name

Research Site

City

Tel Aviv

ZIP/Postal Code

6423906

Country

Israel

Facility Name

Research Site

City

Szczecin

ZIP/Postal Code

70-111

Country

Poland

Facility Name

Research Site

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

Research Site

City

Hospitalet deLlobregat

ZIP/Postal Code

08907

Country

Spain

Facility Name

Research Site

City

Lund

ZIP/Postal Code

22185

Country

Sweden

Facility Name

Research Site

City

Cambridge

ZIP/Postal Code

CB2 0QQ

Country

United Kingdom

Facility Name

Research Site

City

Edinburgh

ZIP/Postal Code

EH4 2XR

Country

United Kingdom

Facility Name

Research Site

City

London

ZIP/Postal Code

SE1 9RT

Country

United Kingdom

Facility Name

Research Site

City

Manchester

ZIP/Postal Code

M20 4BX

Country

United Kingdom

Facility Name

Research Site

City

Sutton

ZIP/Postal Code

SM2 5PT

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

35170751

Citation

Tattersall A, Ryan N, Wiggans AJ, Rogozinska E, Morrison J. Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer. Cochrane Database Syst Rev. 2022 Feb 16;2(2):CD007929. doi: 10.1002/14651858.CD007929.pub4.

Results Reference

derived

PubMed Identifier

32073956

Citation

Penson RT, Valencia RV, Cibula D, Colombo N, Leath CA 3rd, Bidzinski M, Kim JW, Nam JH, Madry R, Hernandez C, Mora PAR, Ryu SY, Milenkova T, Lowe ES, Barker L, Scambia G. Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial. J Clin Oncol. 2020 Apr 10;38(11):1164-1174. doi: 10.1200/JCO.19.02745. Epub 2020 Feb 19.

Results Reference

derived

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

19238149

Citation

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.

Results Reference

derived

Links:

URL

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=193&filename=CSR_Synopsis_D0810C00012.pdf

Description

CSR_Synopsis_D0810C00012.pdf

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

Ovarian Neoplasms

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial