NCT00628251 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2019-12-05

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression Free Survival (PFS)

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outcome · POSTED

Objective Response Rate (ORR)

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outcome · POSTED

Disease Control Rate

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outcome · POSTED

Overall Duration of Response

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outcome · POSTED

Best Percentage Change in Tumour Size

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outcome · POSTED

Best Percentage Change From Baseline in CA-125 Levels

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outcome · POSTED

Confirmed RECIST Response and/or CA-125 Response

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Progression Free Survival (PFS)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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
healthy Volunteers: false
maximum Age: 130 Years
minimum Age: 18 Years
sex: FEMALE
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
AZD2281 Oral 200 mg BID
intervention Names
Drug: AZD2281
label
1
type
EXPERIMENTAL
description
Liposomal Doxorubicin
intervention Names
Drug: Liposomal Doxorubicin
label
2
type
ACTIVE_COMPARATOR
description
AZD2281 Oral 400 mg BID
intervention Names
Drug: AZD2281
label
3
type
EXPERIMENTAL

interventions

arm Group Labels
3
description
400mg Oral twice daily
name
AZD2281
other Names
Olaparib
type
DRUG
arm Group Labels
2
description
50mg/m2 Monthly Intravenous
name
Liposomal Doxorubicin
other Names
Doxil®
type
DRUG
arm Group Labels
1
description
200mg oral twice daily
name
AZD2281
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 97
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

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)
measure
Progression Free Survival (PFS)
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 Outcomes

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.
measure
Objective Response Rate (ORR)
time Frame
At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
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
measure
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)
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.)
measure
Overall 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)
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
measure
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)
description
Best percentage change in cancer antigen 125 (CA-125) levels
measure
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)
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.
measure
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)
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
measure
Overall Survival (OS)
time Frame
At the time of the cut-off for the final analysis of overall survival (30 April 2010)
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.
measure
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)
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.
measure
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)
description
Best HRQoL response using the FOSI endpoint. Improvement was defined as a change from baseline of greater than or equal to +3.
measure
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)

Full 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.

Source references

references

citation
Newhouse R, Nelissen E, El-Shakankery KH, Rogozinska E, Bain E, Veiga S, Morrison J. Pegylated liposomal doxorubicin for relapsed epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Jul 5;7(7):CD006910. doi: 10.1002/14651858.CD006910.pub3.
pmid
37407274
type
DERIVED
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.
pmid
35170751
type
DERIVED
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.
pmid
32073956
type
DERIVED
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.
pmid
26961146
type
DERIVED
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.
pmid
23922302
type
DERIVED
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.
pmid
19238149
type
DERIVED