Clinical trial NCT00628251: Dose-finding Study Comparing Efficacy and Safety of a PARP Inhibitor Against Doxil in BRCA+ve Advanced Ovarian Cancer
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Neoplasms
Keywords: Advanced ovarian cancer
BRCA1 protein
BRCA2 protein
Poly(ADP ribose) polymerases
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2008-03-05
Enrollment: 97
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 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:
measure: Objective Response Rate (ORR)
timeFrame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
measure: Disease Control Rate
timeFrame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
measure: Overall Duration of Response
timeFrame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
measure: Best Percentage Change in Tumour Size
timeFrame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
measure: Best Percentage Change From Baseline in CA-125 Levels
timeFrame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
measure: Confirmed RECIST Response and/or CA-125 Response
timeFrame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
measure: Overall Survival (OS)
timeFrame: At the time of the cut-off for the final analysis of overall survival (30 April 2010)
measure: Best Quality of Life (QoL) Response for Trial Outcome Index (TOI)
timeFrame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
measure: Best QoL Response for Total Functional Analysis of Cancer Therapy - Ovarian (FACT-O)
timeFrame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
measure: Best QoL Response for FACT-O Symptom Index (FOSI)
timeFrame: At the time that 57 PFS events had occurred (Data cut-off for primary analysis of PFS: 15 September 2009)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Boca Raton
country: United States
facility: Research Site
state: Florida
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: New York
country: United States
facility: Research Site
state: New York
city: Houston
country: United States
facility: Research Site
state: Texas
city: East Melbourne
country: Australia
facility: Research Site
city: Melbourne, Parkville
country: Australia
facility: Research Site
city: Randwick
country: Australia
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Köln
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Ramat Gan
country: Israel
facility: Research Site
city: Tel Aviv
country: Israel
facility: Research Site
city: Szczecin
country: Poland
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Hospitalet deLlobregat
country: Spain
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Edinburgh
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Sutton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Jane Robertson, BSc, MBCHB, MD
role: STUDY_DIRECTOR
affiliation: Royal Marsden NHS Foundation Trust
name: Stan Kaye, BSc, MB, FRCP, FRCR, SMedSCi
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.