Clinical trial NCT00753545: Assessment of Efficacy of AZD2281 in Platinum Sensitive Relapsed Serous Ovarian Cancer
Official title: Phase II Randomised, Double Blind, Multicentre Study to Assess the Efficacy of AZD2281 in the Treatment of Patients With Platinum Sensitive Relapsed Serous Ovarian Cancer Following Treatment With Two or More Platinum Containing Regimens
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: Serous,
Ovarian cancer,
PARP,
BRCA1,
BRCA2,
Poly(ADP ribose) polymerases,
Platinum sensitive,
Homologous Recombination Deficiency (HRD)
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2008-09-16
Enrollment: 265
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 primary purpose of this study to determine if AZD2281 is effective and well tolerated in maintaining the improvement in your cancer after previous platinum-based chemotherapy


Eligibility criteria: Inclusion Criteria:

* Female patients with histologically diagnosed serous ovarian cancer or recurrent serous ovarian cancer.
* Patients must have completed at least 2 previous courses of platinum containing therapy; the patient must have been platinum sensitive to the penultimate chemo regimen.
* For the last chemotherapy course prior to enrolment on the study, patients must have demonstrated an objective stable maintained response (partial or complete response) and this response needs to be maintained until completion of chemotherapy.
* Patients must be treated on the study within 8 wks of completion of their final dose of the platinum containing regimen.

Exclusion Criteria:

* Previous treatment with PARP inhibitors including AZD2281
* Patients with low grade ovarian carcinoma.
* Patients who have had drainage of their ascites during the final 2 cycles of their last chemotherapy regimen prior to enrolment on the study
* Patients receiving any chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study entry (or a longer period depending on the defined characteristics of the agents used).

Primary outcomes:
measure: Progression Free Survival (PFS) (According to Response Evaluation Criteria in Solid Tumours [RECIST])
timeFrame: Radiologic scans performed at baseline then every 12 weeks (+/- 1 week) for the first 60 weeks, then every 24 weeks (+/-1 week) thereafter, assessed maximum up to 14 months.
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Follow up every 12 weeks post progression, assessed maximum up to 90 months.
measure: Objective Response Rate (ORR) (According to RECIST)
timeFrame: Radiologic scans performed at baseline then every 12 weeks (+/- 1 week) for the first 60 weeks, then every 24 weeks (+/-1 week) thereafter, assessed maximum up to 14 months.
measure: Disease Control Rate
timeFrame: Assessed at 24 weeks. Radiologic scans performed at baseline, week 12 (+/- 1 week) and week 24 (+/- 1 week).
measure: Duration of Response
timeFrame: Radiologic scans performed at baseline then every 12 weeks (+/- 1 week) for the first 60 weeks, then every 24 weeks (+/-1 week) thereafter, assessed maximum up to 14 months.
measure: Percentage Change From Baseline in Tumour Size at Week 24
timeFrame: Radiologic scans performed at baseline then every 12 weeks (+/- 1week) for the first 60 weeks, then every 24 weeks (+/-1 week) thereafter, assessed maximum up to 14 months.
measure: Best Percentage Change in Cancer Antigen 125 (CA-125) Levels
timeFrame: CA-125 was measured at baseline then every 28 days on treatment, assessed maximum up to 14 months.
measure: Best Objective Response
timeFrame: Radiologic scans performed at baseline then every 12 weeks (+/- 1week) for the first 60 weeks, then every 24 weeks (+/- 1 week) thereafter, assessed maximum up to 14 months.
measure: RECIST and CA-125 Response Separately and Combined
timeFrame: Radiologic scans performed at baseline then every 12 weeks (+/- 1week) for the first 60 weeks, then every 24 weeks (+/- 1 week) thereafter and monthly for CA-125 measurements, assessed maximum up to 14 months.
measure: Time to Earlier of CA-125 or RECIST Progression
timeFrame: Radiologic scans performed at baseline then every 12 weeks (+/- 1 week) for the first 60 weeks, then every 24 weeks (+/- 1 week) thereafter and monthly for CA-125 measurements, assessed maximum up to 14 months.
measure: Improvement Rate for FACT-O Symptom Index (FOSI)
timeFrame: Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression, assessed maximum up to 14 months.
measure: Improvement Rate for Trial Outcome Index (TOI)
timeFrame: Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression, assessed maximum up to 14 months.
measure: Improvement Rate for Total Functional Analysis of Cancer Therapy - Ovarian (FACT-O)
timeFrame: Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression, assessed maximum up to 14 months.
measure: FACT-O Symptom Index (FOSI) Time to Worsening
timeFrame: Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression, assessed maximum up to 14 months.
measure: Trial Outcome Index(TOI)Time to Worsening
timeFrame: Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression, assessed maximum up to 14 months.
measure: Functional Analysis of Cancer Therapy - Ovarian (FACT-O) Time to Worsening
timeFrame: Patient reported outcome questionnaire completed at baseline then every 28 days up to disease progression, assessed maximum up to 14 months.
Other outcomes:
Locations:
city: Berkeley
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: West Hollywood
country: United States
facility: Research Site
state: California
city: Sunrise
country: United States
facility: Research Site
state: Florida
city: West Palm Beach
country: United States
facility: Research Site
state: Florida
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: New York
country: United States
facility: Research Site
state: New York
city: Providence
country: United States
facility: Research Site
state: Rhode Island
city: Adelaide
country: Australia
facility: Research Site
city: East Bentleigh
country: Australia
facility: Research Site
city: Heidelberg
country: Australia
facility: Research Site
city: Melbourne
country: Australia
facility: Research Site
city: Nambour
country: Australia
facility: Research Site
city: Randwick
country: Australia
facility: Research Site
city: South Brisbane
country: Australia
facility: Research Site
city: Toorak Gardens
country: Australia
facility: Research Site
city: Innsbruck
country: Austria
facility: Research Site
city: Wein
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Brussels
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Sherbrooke
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Brno
country: Czechia
facility: Research Site
city: Brno
country: Czechia
facility: Research Site
city: Olomouc
country: Czechia
facility: Research Site
city: Praha 10
country: Czechia
facility: Research Site
city: Tallinn
country: Estonia
facility: Research Site
city: Tartu
country: Estonia
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Caen Cedex
country: France
facility: Research Site
city: Lyon Cedex 08
country: France
facility: Research Site
city: Nantes
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Reims Cedex
country: France
facility: Research Site
city: Bonn
country: Germany
facility: Research Site
city: Düsseldorf
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Freiburg
country: Germany
facility: Research Site
city: Göttingen
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Kiel
country: Germany
facility: Research Site
city: Marburg
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Rostock
country: Germany
facility: Research Site
city: Ulm
country: Germany
facility: Research Site
city: Wiesbaden
country: Germany
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Holon
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Nahariya
country: Israel
facility: Research Site
city: Ramat Gan
country: Israel
facility: Research Site
city: Tel-Aviv
country: Israel
facility: Research Site
city: Zerifin
country: Israel
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Grzepnica
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Poznan
country: Poland
facility: Research Site
city: Poznan
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Szczecin
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Baia Mare
country: Romania
facility: Research Site
city: Cluj-Napoca
country: Romania
facility: Research Site
city: Iasi
country: Romania
facility: Research Site
city: Suceava
country: Romania
facility: Research Site
city: Barnaul
country: Russian Federation
facility: Research Site
city: Ekaterinburg
country: Russian Federation
facility: Research Site
city: Obninsk
country: Russian Federation
facility: Research Site
city: Orenburg
country: Russian Federation
facility: Research Site
city: Perm
country: Russian Federation
facility: Research Site
city: Pyatigorsk
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Voronezh
country: Russian Federation
facility: Research Site
city: Córdoba
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Donetsk
country: Ukraine
facility: Research Site
city: Kharkiv Region
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Lutsk
country: Ukraine
facility: Research Site
city: Odesa
country: Ukraine
facility: Research Site
city: Odesa
country: Ukraine
facility: Research Site
city: Ternopil
country: Ukraine
facility: Research Site
city: Uzhhorod
country: Ukraine
facility: Research Site
city: Dundee
country: United Kingdom
facility: Research Site
city: Edinburgh
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Northwood
country: United Kingdom
facility: Research Site
city: Sutton
country: United Kingdom
facility: Research Site
city: Wirral
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Mika Sovak, BSc, MBCHB, MD
role: STUDY_DIRECTOR
affiliation: University College, London
name: Prof Jonathan A Lederman
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: Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Bennett B, Parry D, Spencer S, Mann H, Matulonis U. Quality of life during olaparib maintenance therapy in platinum-sensitive relapsed serous ovarian cancer. Br J Cancer. 2016 Nov 22;115(11):1313-1320. doi: 10.1038/bjc.2016.348. Epub 2016 Nov 8.
citation: Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Rowe P, Lowe E, Hodgson D, Sovak MA, Matulonis U. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol. 2016 Nov;17(11):1579-1589. doi: 10.1016/S1470-2045(16)30376-X. Epub 2016 Sep 9.
citation: Matulonis UA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Parry D, Grinsted L, Ledermann JA. Olaparib maintenance therapy in patients with platinum-sensitive, relapsed serous ovarian cancer and a BRCA mutation: Overall survival adjusted for postprogression poly(adenosine diphosphate ribose) polymerase inhibitor therapy. Cancer. 2016 Jun 15;122(12):1844-52. doi: 10.1002/cncr.29995. Epub 2016 Apr 8.
citation: Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott CL, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Dougherty B, Orr M, Hodgson D, Barrett JC, Matulonis U. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol. 2014 Jul;15(8):852-61. doi: 10.1016/S1470-2045(14)70228-1. Epub 2014 May 31.
citation: Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Macpherson E, Watkins C, Carmichael J, Matulonis U. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012 Apr 12;366(15):1382-92. doi: 10.1056/NEJMoa1105535. Epub 2012 Mar 27.
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.