Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

AZD2281

Liposomal Doxorubicin

Jane Robertson, BSc, MBCHB, MD

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

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.

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

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

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)

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.

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

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.)

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 in cancer antigen 125 (CA-125) levels

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.

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

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

AstraZeneca

AEs reported = all events up to OS data cut-off. After PFS data cut-off, AEs only collected for olaparib and cross-over groups. The safety profile of these 2 groups at OS was consistent with that at time of PFS. One patient was recorded as crossing over to olaparib but not receiving cross-over treatment.

Olaparib (AZD2281) 200 mg oral capsules twice daily

Olaparib 200 mg bd

Olaparib (AZD2281) 400 mg oral capsules twice daily

Olaparib 400 mg bd

Liposomal doxorubicin 50 mg/m2 intravenously every 4 weeks

Total

Age, Continuous

Sex: Female, Male

African-Caribbean

Ashkenazi Jewish

Sephardic Jewish

Not applicable

Other

Race/Ethnicity, Customized

Deleterious BRCA1 mutation

Deleterious BRCA2 mutation

BRCA status

The AEs reported include all events up to the OS data cut-off. After the PFS data cut-off, AEs were only collected for the olaparib and cross-over groups. The safety profile of these 2 groups at OS was consistent with that at the time of PFS.

Paula del Rosario

Analysis of olaparib 200 or 400 mg bd (n=64) versus liposomal doxorubicin (n=33). A hazard ratio \< 1 favours olaparib.

Analysis of olaparib 200 (n=32) versus liposomal doxorubicin (n=33). A hazard ratio \< 1 favours olaparib.

Analysis of olaparib 400 (n=32) versus liposomal doxorubicin (n=33). A hazard ratio \< 1 favours olaparib.

Progression Free Survival (PFS)

Analysis of olaparib 200 or 400 (n=64) versus liposomal doxorubicin (n=33).

Analysis of olaparib 200 (n=32) versus liposomal doxorubicin (n=33).

Analysis of olaparib 400 (n=32) versus liposomal doxorubicin (n=33).

Complete response

Number of Partial responders

Objective Response Rate (ORR)

Disease Control Rate

Olaparib (AZD2281) 200 or 400 mg oral capsules twice daily

Olaparib 200 mg bd + Olaparib 400 mg bd,

Duration of response is analysed for patients experiencing a response.

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

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial